Category Archives: Testosterone

Indian J Urol. 2014 Jan-Mar; 30(1): 27.

Department of Urology, New York Presbyterian Hospital, Weill Cornell Medical College, Starr 900, New York, NY, USA

Department of Urology, New York Presbyterian Hospital, Weill Cornell Medical College, Starr 900, New York, NY, USA

Department of Urology, New York Presbyterian Hospital, Weill Cornell Medical College, Starr 900, New York, NY, USA

Department of Urology, New York Presbyterian Hospital, Weill Cornell Medical College, Starr 900, New York, NY, USA

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Testosterone replacement therapy (TRT) is a widely used treatment for men with symptomatic hypogonadism. The benefits seen with TRT, such as increased libido and energy level, beneficial effects on bone density, strength and muscle as well as cardioprotective effects, have been well-documented. TRT is contraindicated in men with untreated prostate and breast cancer. Men on TRT should be monitored for side-effects such as polycythemia, peripheral edema, cardiac and hepatic dysfunction.

Keywords: Hypogonadism, side-effects, testosterone replacement therapy

Testosterone has many beneficial effects, including increasing bone strength and density, inducing hematopoiesis, driving sexual function and libido, providing a cardioprotective effect and increasing muscle strength.[1] Testosterone levels are known to decline as men age. The Baltimore Longitudinal Study of Aging reported the incidence of hypogonadism as 20% in men over 60 years of age, 30% in men over 70 years and 50% in men over 80 years of age.[2]

As men age, a decline in testicular production of testosterone are seen, as well as an increase in sex hormone binding globulin, both of which act to decrease bioavailable testosterone.[3] With this gradual decline, the beneficial effects of testosterone could be diminished and negatively affect physical and emotional well-being. Testosterone replacement therapy (TRT) is a reasonable treatment option often discussed for men with low testosterone levels and symptoms of hypogonadism. When replaced, many of the positive effects of testosterone are regained.[4] These positive results have led to a drastic increase in the use of testosterone replacement for men with symptomatic hypogonadism, though long-term data is lacking on the safety.

While the beneficial effects of testosterone are rarely disputed and widely publicized, there is a paucity of the literature on the risks of testosterone use. Any man who has a comorbidity that precludes TRT should be informed of all risks. Factors such as exacerbation of prostate cancer, male breast cancer, worsening benign prostatic hyperplasia (BPH), polycythemia and an increased risk of obstructive sleep apnea (OSA) should be considered when administering TRT to a patient. The goal of this review is to highlight the risks and summarize the current literature on safety of TRT.

One of the major risk factors associated with the administration of testosterone supplementation is its effect on the prostate. We know the prostate to be an androgen-dependent gland and conversely, anti-androgen agents can decrease prostate volume in patients with BPH. As the population continues to age, both the incidence of BPH and late-onset male hypogonadism will continue to rise and practitioners will need to be comfortable with counseling men on the effect of TRT on the prostate.[5]

In a landmark randomized, double-blind, placebo-controlled trial of 44 hypogonadal men, Marks et al. showed that TRT for 6 months improves serum androgen levels, but had little effect on prostate tissue androgen levels, tissue biomarkers and/or gene expression.[6] Testosterone supplementation has been shown to increase prostate size by 12%,[7] but lower urinary tract symptoms (LUTS) and urinary retention do not worsen in men on testosterone therapy.[8,9] Similarly, the presence of hypogonadism in 312 men with reportable LUTS was not predictive of worsening International Prostate Symptom Scores (IPSS) or maximal urinary flow rates.[10]

In fact, some series report an improvement in LUTS after 1 year of TRT.[11,12] In the most recent, randomized controlled trial, 52 men were randomly assigned to receive TRT. At 1 year, the 23 men randomized to 250 mg of testosterone enanthate every 4 weeks reported significant improvements in IPSS and maximal urinary flow rates compared with baseline and controls.[12] At no point in this trial did any patient require additional medication or suffer urinary retention.

While older men on testosterone therapy do have an increase in overall prostate size, this increase in size does not differ from the increase in prostatic hypertrophy seen in elderly men not on testosterone therapy.[13] Taken together, TRT does not appear to grossly worsen LUTS and is not contraindicated in men diagnosed with BPH.

It has been over 60 years since Hodges and Huggins described a relationship between serum testosterone levels and prostate cancer progression.[14] Later in 1982, Fowler and Whitmore reported that exogenous testosterone given to patients with metastatic prostate cancer had worse outcomes.[15] Today androgen deprivation therapy remains a cornerstone of treatment for men with advanced prostate cancer, so it is no surprise that TRT is contraindicated in men with diagnosed prostate cancer, as well as high-risk patients, which includes men with first-degree relatives with prostate cancer and African-Americans who have a prostate-specific antigen (PSA) >3 ng/mL.[4,16]

Recently, there has been a paradigm shift whereby TRT usage has increased despite this potential risk. Many longitudinal studies investigating the relationship of endogenous testosterone levels and subsequent risk of prostate cancer failed to find any association.[17] As such, prostate cancer incidence in men on testosterone therapy is similar to men not on testosterone therapy.[18,19] Similarly, in a 3-year prospective trial, the incidence of prostate cancer was similar among men receiving TRT and controls.[20] In a large meta-analysis of 18 prospective studies that included over 3500 men, there was no association between serum androgen levels and the risk of prostate cancer development.[21] Morgentaler et al. proposed a saturation theory where prostate growth becomes insensitive to changes at normal androgen levels due to saturation of the androgen-receptor; however, there is exponential growth at castrate levels.[22] This theory may explain why testosterone does not directly cause prostate cancer,[23] but it has been shown to accelerate the development of prostate cancer.[24,25]

For premalignancy, prostatic intraepithelial neoplasia (PIN) appears to be a risk factor for developing prostate cancer, however this association has been mostly demonstrated for high-grade disease.[26,27] There is a lack of long-term data on the use of TRT in men with PIN. In one study, 12 months after TRT, only one patient out of 20 men with previous PIN developed overt prostate cancer.[28]

For men who have previously undergone definitive treatment for prostate cancer, the usage of TRT is becoming more accepted. TRT does not appear to increase cancer recurrence in hypogonadal men following radical prostatectomy.[29] In the most recent study by Pastuszak et al., the authors retrospectively reviewed a cohort of 103 men who underwent prior radical prostatectomy and were treated with TRT. Despite a significant increase in PSA in men receiving TRT, there were twice as many cancer recurrences in the control group after 36 months of follow-up.[30]

For men with untreated prostate cancer on active surveillance, TRT remains controversial. However, several studies have shown that TRT is not associated with progression of prostate cancer as evidenced by either PSA progression or gleason grade upstaging on repeat biopsy.[31,32] In the most recent study by Morgentaler et al., 13 men with symptomatic hypogonadism and untreated prostate cancer received TRT for a median of 2.5 years and no local prostate cancer progression or distant disease was observed.[33]

While there have been reports of metastatic prostate cancer in older men who are on testosterone therapy,[20] these are mostly anecdotal. Because of this potential risk, practitioners are often reluctant to administer testosterone in patients they believe may be at high risk for prostate cancer or whom they suspect may have the low-grade disease. Men on TRT should have frequent PSA monitoring; any major change in PSA (>1 ng/mL) within the first 3-6 months may reflect the presence of a pre-existing cancer and warrants cessation of therapy.[34] Current guidelines on the frequency of PSA monitoring and role of pre-treatment transrectal ultrasound guided prostate biopsy are lacking.[35] Taken together, there has been consistent rejection that TRT causes development of prostate cancer in men, however administration of TRT for hypogonadal men previously treated for high-risk prostate cancer should be taken with caution.

While there is no known physiologic link of testosterone directly to the development of breast cancer, it has been suggested that high levels of testosterone may lead to increased aromatization to an active derivative of estrogen, which ultimately may stimulate breast tissue receptors and increase the risk of male breast cancer.[36]

The role of testosterone in breast cancer development is yet to be fully understood.[37] Currently, several case reports exist[38] and one retrospective review sites an incidence 11% in 45 men on long term TRT over 10 years.[39] Future prospective studies with longer follow-up will determine if such association between TRT and male breast cancer truly exists.

Testosterone leads to an increase in hemoglobin by as much as 5-7%[1,25] through its effect on the production of erythropoietin, which can dramatically improve symptoms of anemia in men.[40,41]

Studies looking at the occurrence of polycythemia as a negative side-effect in men on testosterone therapy are rare. Despite this, polycythemia is an accepted side-effect of TRT. While testosterone exerts a positive effect in men with baseline anemia, it can lead to polycythemia in over 20% of men treated on TRT.[42] Polycythemia may lead to an increased incidence of vascular events, including stroke, myocardial infarction and deep vein thrombosis with possible pulmonary embolus.[42] While these complications are all possible with polycythemia, their theoretical occurrence has not been demonstrated to occur in men on TRT.[43]

Because of this risk of polycythemia, men undergoing TRT should not only have their complete blood count (CBC) monitored during their therapy, but should also have a baseline CBC drawn before testosterone therapy is initiated. While on testosterone therapy, if the hematocrit (HCT) rises greater than 54%, testosterone therapy should be held until the HCT normalizes. If it is restarted after normalization, it should be performed so at a lower dose with continued careful monitoring.[16]

OSA is a risk associated with TRT in men, but its etiology is not particularly well understood. While some studies suggested that there is no association between OSA and TRT,[44] others have demonstrated that that OSA occurs in men undergoing TRT and when supplementation is stopped, the OSA resolves.[45]

While no clear link has been established, men on TRT should be counseled on the risk of potential OSA when therapy is started. They should be monitored for increased symptoms, such as snoring while sleeping or fatigue. If patients starting TRT already carry a diagnosis of OSA, physicians should counsel these patients that TRT may worsen their symptoms. While, OSA remains to be a relative contraindication to initiation of TRT, more research needs to be completed on this association in order to gain a better understanding of its etiology if there is one at all.

The systemic effects of TRT may be exacerbated in men with limited cardiovascular reserve. Previous dogma held that androgens could have atherogenic potential. In a randomized, placebo-controlled trial, Basaria et al. reported an increased risk of cardiovascular events in men randomized to TRT; however, this small cohort had a high prevalence of chronic disease.[46] Today, current literature suggests that TRT has a neutral to beneficial effect on reported cardiovascular events.[47,48] Because some men may have a limited cardiovascular capacity, clinicians prescribing TRT must be cautious with respect to its ability to cause edema.[49] Until date, no longitudinal studies examine the impact of TRT on the cardiovascular system, however some studies suggest that TRT may serve as an adjunct rehabilitative therapy in patients with congestive heart failure (CHF).[50,51,52]

While topical testosterone delivery systems avoid first-pass hepatic metabolism, there remains concern regarding TRT in patients with chronic liver disease. The majority of reports of liver toxicity and jaundice are limited to orally-administered alkylated forms of testosterone.[53] However, a small prospective study representing a cohort of cirrhotic patients demonstrated topical gels to be safe and efficacious.[54] It has also been shown that TRT may improve hepatic function in patients with end-stage liver disease.[55] Because of these mixed results, clinicians should be aware of the possible risks associated with TRT in men with hepatic dysfunction and counsel these men accordingly.

Because TRT is known to cause water retention, caution with testosterone use in patients with chronic renal insufficiency is often advised. In patients with end-stage renal disease (ESRD) on dialysis, fluid shifts are less of a concern in patients on TRT since the fluid retention can be handled with dialysis. While polycythemia may be an adverse side-effect, this is a potential benefit in patients with chronic renal failure and anemia.[56] Furthermore, the half-life of testosterone elimination after withdrawal appears similar between patients with and without ESRD.[56] Few studies have assessed the effects of TRT in patients with chronic kidney disease; however, small studies have suggested that TRT has anabolic effects among ESRD patients, even in the absence of hypogonadism. Aside from frequent monitoring of congestive symptoms and peripheral edema in this select population, TRT appears to be safe for patients with chronic kidney disease without dose adjustment.[57]

When testosterone reaches supra-therapeutic levels, aggressive behavior and increased rates of suicide among adolescent users have been reported;[58] however, no study has documented a negative impact on cognition in men patients receiving TRT. In fact, studies have shown that testosterone replacement to eugonadal levels may improve or stabilize cognitive function.[59,60,61] Lower levels of testosterone have a negative impact on spatial and verbal abilities, as well as cognitive function; therefore, it is no surprise that normalizing testosterone levels results in cognitive improvements.[62,63]

With exogenous testosterone supplementation, the pulsatile release of gonadotropin-releasing hormone is blunted and the release of follicle-stimulating hormone and luteinizing hormone are depressed. As such, a decrease in spermatogenesis is seen.[64] While this effect may not be of importance to many men who have completed their families, physicians prescribing TRT need to be aware.

When serum levels of testosterone are increased, a concurrent increase in the secretion of sebum occurs, which can lead to acne. Despite this known association, this effect is typically minimal.[65] Case reports regarding testosterone supplementation leading to changes in hair patterns have been documented; however no randomized, placebo-controlled trials exist. Various topical and intramuscular injectable forms of testosterone are associated with a variety of skin reactions, mainly erythema and pruritus in up to 60% of users.[20]

TRT is associated with external, physical changes in the men. Exogenous testosterone is known to cause an imbalance in the hypothalamic-pituitary axis. As such, testosterone can be converted to estrogen by aromatization. Excess estrogens may lead to gynecomastia and/or breast pain, both of which may be seen in 10-25% of men on TRT.[66] The ratio of estradiol to androgens is the key factor in the development of gynecomastia rather than absolute increases in androgens themselves.[66] Clinicians must be aware of non-iatrogenic causes of gynecomastia and therefore the appropriate work-up should be sought out to rule out other pathology, especially if there is any breast tenderness or unilateral gynecomastia. Only a few case-reports describe a relationship between male breast cancer and TRT.[38,39]

In addition, excess estrogens may cause an increase in visceral obesity. With vigilant monitoring of serum estrogen levels, TRT has been shown to promote weight loss.[67] Well-known to many prescribers of TRT is a risk of water retention and/or edema. The etiology of this association remains unclear to date.[68] The degree of retention is generally mild. As mentioned above, men on TRT with a history of CHF should follow closely[69].

TRT has numerous benefits that can great enhance a patient's quality-of-life. Before prescribing TRT, one must be conscientious of its adverse effects. Data on the safety of TRT specific to our aging population is not currently available; however TRT has been linked to prostate cancer, BPH, polycythemia and OSA. A full assessment of the morbidity of TRT would require a large-scale, randomized, controlled trial. To date, physicians remain in a quandary about the best approach to care for men with symptoms of hypogonadism. TRT, when given to appropriately selected patients with vigilant monitoring as outlined in this review and in , can bring improvements in quality-of-life, energy level, libido, muscle mass, cognition and bone density.

Potential risks of TRT and associated monitoring strategies

Source of Support: Nil

Conflict of Interest: None declared.

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Risks of testosterone replacement therapy in men

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CrazyBulk Reviews 2022: How Good Is the Legal Steroids Brand? - Cleveland Scene

Following the initial devastation of the coronavirus pandemic, the U.S. economy has so far engineered an impressive recovery. Although not every metric is perfectly aligned, we can say this much: the early (and understandable) prognostications of doom and gloom did not materialize. However, with so many unknowns heading into 2022, investors may want to adjust their capitalization strategy. Here, were going to discuss ideas for best small-cap stocks to buy.

Why downsize your investment opportunities? First of all, many people have long operated under the thesis of the small-cap effect or the tendency for smaller publicly traded companies to outperform their large-cap counterparts over time. Early this year, the Wall Street Journal provided some contextual evidence for this phenomenon, noting that the best small-cap stocks within the S&P 500 index did indeed outperform their larger rivals.

Another reason to consider downsizing is what Id term the George W. Bush effect of lower expectations. Heading into his presidential debate with former Vice President Al Gore, Bushs team attempted to raise expectations so high for Gore while downplaying them for Bush. A similar situation is going on with large caps as many want to see even more robust growth from them. That might not happen, though, boosting the best small-cap stocks.

Further, everyone thats following the market knows that initial public offerings became, well, endemic in 2021. From traditional offerings to direct listings to special purpose acquisition companies (SPACs), weve seen it all and then some. However, the record year for IPOs may produce an unintended consequence. Mainstream investors are overwhelmed with flashy opportunities, while the best small-cap stocks are flying under the radar, waiting for their turn to shine.

Finally, smaller companies may be able to respond quickly and adapt to shifting market conditions. On the other hand, large-cap firms must answer to powerful stakeholders who may hinder necessary change. Therefore, as we greet the new year, dont forget to consider these ideas for best small-cap stocks to buy.

Of course, nothing in the market is without risk. While the best small-cap stocks may outperform blue chips over time, when circumstances turn volatile, smaller tends to be a liability. Primarily, this is because they lack the resources of larger enterprises. Thus, due diligence is always critical.

Typically, analysts regard small caps as companies that feature a market cap between $300 million to $2 billion. In that context, Im cheating a tad bit with CommVault Systems, which at time of writing runs a hair over $3 billion. Nevertheless, CommVault is listed on many articles of best small-cap stocks, including exchange-traded funds (ETFs) focusing on this subsegment.

But thats not the main reason Im including it here. Rather, the company, which specializes in data protection and data management solutions, is incredibly relevant. For instance, lost data from cyberattacks can cost enterprises millions. Further, smaller organizations that participated in last years grand telecommuting experiment may be at higher risk if their employees dont practice proper security measures.

As well, even the biggest firms can suffer significant damage due to outages and other unforeseen incidents. Therefore, with so much valuable assets transmitting across digital lines, its more imperative than ever for corporations of any size to protect themselves. This dynamic makes CVLT one of the best small-cap stocks to buy, regardless of whatevers lying around the corner in 2022.

More of a traditional small-cap firm with a time-of-writing market value of $557.5 million, ANI Pharmaceuticals specializes in the development, manufacturing and marketing of high-quality branded and prescription generic drugs. Obviously, the pharmaceutical space enjoyed significant attention mostly due to the Covid-19 treatment and vaccination race. With much of that fervor fading, though, ANI can shine in a post-pandemic environment.

Should omicrons higher transmissibility (but less severe symptoms) profile be indicative of the twilight of the Covid period, resources will again shift back toward non-pandemic-related healthcare needs. Further, prescription generics should play an important role in the post-pandemic era. If theres anything that we can rely on, its that healthcare costs seemingly have an exclusive directional trajectory, up.

Moreover, I like companies where the insiders believe in their business, enough so that theyre buying up additional equity. No, insider buying isnt the be-all, end-all for best small-cap stocks. However, its an encouraging sign that since 2020, the transactions that have occurred are buys, not sells. So, if youre the practice-what-you-preach type, you might want to consider ANIP.

Let me caveat the idea of including Endo International on your radar of best small-cap stocks to buy with a warning: This is not going to be any easy opportunity. On a year-to-date basis, ENDP stock has shed 42%.

On the positive side, the red ink means that the market cap for Endo is $1.09 billion, which means its no longer on the borderline of what would be considered a small-cap firm.

But is it one of the best small-cap stocks to buy? As the top holding of the Invesco S&P SmallCap 600 Equal Weight ETF (NYSEARCA:EWSC), plenty of folks at a much higher paygrade than me certainly think so. And as I mentioned earlier with ANI Pharmaceuticals, as the Covid-19 period fades into the rearview mirror, Endos specialty in generics and specialty-branded pharmaceuticals should help lift ENDP stock.

But heres something uniquely intriguing. One of Endos products is Testopel, a testosterone replacement therapy. According to a report published on ScienceDaily, a study of patients hospitalized due to COVID-19 suggests that the disease might deteriorate mens testosterone levels.

Further, many male Covid patients reported loss of libido. Cynically, then, ENDP should rise to the occasion.

As a recent uplisting from the over-the-counter market to the Nasdaq exchange, I consider Ranger Oil Corp a spiritual IPO. True, on paper, an IPO represents the first time a company distributes its equity shares to the public. On the other hand, an uplisting from the pink sheets to a proper exchange is more of an introduction to a wider audience.

But isnt that one of the main points about an IPO? After all, privately held enterprises can raise funds through venture capitalists and other means. However, going public allows firms to reach the widest audience possible, netting the largest raises possible (all other things being equal). So with Ranger Oil being a Nasdaq play, I have higher expectations for it in 2022.

Still, some might question its inclusion on a list of best small-cap stocks to buy considering that the oil and gas business is losing sentiment against renewable energy firms. In recent years, renewables have become much more economically viable due to rising technology and lower costs.

However, the high energy density of fossil fuels means they could be surprisingly relevant for many, many years to come. Therefore, if youve got some loose change, you might want to put it to work with Ranger Oil.

Customers Bancorp is a perplexing idea among best small-cap stocks and not just because Im again playing a little loose with the definition of small. At a few ticks under $2 billion, Customers Bancorp may be poised to enter the mid-cap range fairly soon.

And that notion isnt out of the question. CUBI stock has been a high-flyer in 2021, gaining almost 218% since the January opener. Since Im not the biggest fan of buying into strength after a particularly robust rally, Im personally a bit hesitant on the opportunity.

Nevertheless, some folks might be encouraged with the outsized performance. Certainly, the companys fundamentals justify the premium. For instance, in the first three quarters of this year, Customers Bancorp has already rung up $548.9 million on the top line, exceeding 2020s results by 9.3%.

To be clear, 2020 wasnt a down year for the company, which saw total revenue increase nearly 41% over 2019s result. So, the firm is on a tear.

Whats interesting about Customers Bancorp is that one of its subsidiaries is building a cryptocurrency infrastructure to better serve its clients. Thats the kind of smart, innovative thinking that will make CUBI possibly more relevant than the competition.

Another high-momentum play among the best small-cap stocks to buy, Ill leave it to you whether you want to acquire shares of Arlo Technologies a wireless smart home security system provider into strength or hold out for a better price. Over the past six months, ARLO gained 31% while in the trailing month, its up 16.5%. Most of those gains occurred in the prior five days, up nearly 13%.

However, like other names among the best small-cap stocks, Arlo justifies its momentum through strong financial performances. During the first three quarters of this year, the company generated revenue of $292.3 million. Considering that 2020 sales amounted to $357.2 million, Arlo only needs a modest tally in the fourth quarter to beat out the prior years result.

Heck, a modest tally should be enough to eclipse 2019 sales, which was $370 million.

Most importantly, though, the outside fundamentals are cynically supportive of ARLO stock. For instance, weve been hearing news reports about San Franciscos brazen property crime spree. Apparently, tolerance for such behaviors is dimming, playing into Arlos hands.

My riskiest and most audacious name among best small-cap stocks, Im going to urge you to perform your own due diligence with KAR Auction Services. Believe me, my feelings will not be hurt if you think this idea is garbage. As the corporate brand entails, KAR Auction provides vehicle auctions and related vehicle remarketing services. Thus, the obvious question is, why?

After all, weve seen an absolutely bonkers season for used car prices. Out of nowhere, buying a car any car during the pre-pandemic period was now a great investment. As you know, this runs counter to the common logic (actually fact) that unless youre buying a truly distinct vehicle, mass-produced vehicles almost always lose their value.

However, as much as people would like to think that car prices are on the cusp of falling, so far, theyve been rising. Indeed, a recent Fortune article bemoaned that rates in the secondhand market keep going higher. Surely, the madness will end in 2022?

Well, maybe not. You see, the computer chips that go into vehicles are of a cheaper, lower-margin variety. Therefore, semiconductor firms would much rather prioritize the consumer-electronics industry, which are much more lucrative.

As much as I hate to say it, KAR could very well be one of the best small-cap stocks to buy for 2022.

On the date of publication, Josh Enomoto did not have (either directly or indirectly) any positions in the securities mentioned in this article.The opinions expressed in this article are those of the writer, subject to the InvestorPlace.comPublishing Guidelines.

A former senior business analyst for Sony Electronics, Josh Enomoto has helped broker major contracts with Fortune Global 500 companies. Over the past several years, he has delivered unique, critical insights for the investment markets, as well as various other industries including legal, construction management, and healthcare.

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7 of the Best Small-Cap Stocks to Buy Before 2022 - InvestorPlace

It is funny how times change. The Guardian has obtained a letter, written in 2003 by Dr Richard Budgett, in which he discusses the consequences of trans women competing in womens sport. Responding to a government inquiry, Budgett, then at the British Olympic Association, states: The effect of allowing male transsexuals to compete as women would be to make competition unfair and potentially dangerous in some sports and would undermine womens sports.

This would have been an interesting answer at the time. It is even more so now. Society has shifted. Language has changed. Budgett is now medical and scientific director at the International Olympic Committee. And his views, according to IOC sources, have evolved particularly when it comes to finding ways to balance the need for inclusion and fairness in sport. A controversial new IOC framework, drawn up in part by Budgett, adopts a strikingly different stance. While stressing that mens and womens competition should be fair and safe, it also tells sports that, until evidence determines otherwise, trans athletes should not be deemed to have an unfair or disproportionate competitive advantage.

Yet the ink had barely dried on that framework document when the US college swimmer Lia Thomas caused a fresh splash in the debate. For her first three years at the University of Pennsylvania the 22yearold swam as a male competitor, making six Ivy League swimming finals though not setting the world alight. But in the past month, competing as a trans woman after taking hormone replacement therapy to lower her testosterone, she has swum the fastest 200- and 500yard times in the US this year.

That, though, tells only half the story. Thomass 200yard time of 1:41:93 ranks as the 17th fastest of all time less than three seconds off the fivetime Olympic medallist Missy Franklins US record of 1:39:10. Meanwhile her 500yard time of 4:34:06 puts her 21st in history and within striking distance of a record set by Katie Ledecky, who is widely regarded as the greatest female swimmer in the sports history.

All roads now lead to the NCAA championships in March, where Thomas could become swimmings first transgender All-American champion. It will be a significant moment for sport and for Thomas, who last week stressed how important it was for her to swim as her authentic self and praised the IOC for promoting inclusivity while keeping competition integrity going.

Others, though, are less happy. According to reports, Thomass teammates were in tears with one explaining: They feel so discouraged because no matter how much work they put in it, theyre going to lose. Meanwhile Swimming World magazines John Lohn said he was uneasy that Ledeckys record was under threat. Simply, she is an icon who changed what was perceived to be attainable, he wrote. The fact that Thomas could break the record of such a onceinageneration athlete confirms the biological advantages she possesses, and their power,.

Thomass surge to the top of the rankings also poses questions of the IOC and NCAA. Remember the female category exists because the performance gap between elite men and elite women is so stark. It starts at around 10%-13% for running and swimming and rises thereafter. That is why most sports require trans women to suppress their testosterone to compete in the female category.

Recent studies, though, suggest that significant strength and muscular advantages remain even after hormone therapy. Thomass performances appear to back that up. Before transitioning, she was not a serious challenge to male records but is now swimming only 2.6% slower than the current 200yard female record. It means, as the developmental biologist Dr Emma Hilton points out, Thomas has gained a significant ranking advantage from switching category.

Is this unfair? In 2003 Budgett thought so. As he put it in his letter: The BOA believes the effect of allowing transsexuals to compete in their acquired sex would be to make competition unfair for women. The physique determined by two or more decades of life as a male would not be significantly changed (in the case of male to female transsexuals) which would eradicate the concept of a level playing field.

Some will argue that sport is never truly fair, that Michael Phelpss big wingspan gave him genetic advantages too. But male puberty provides such a categorical advantage in terms of muscle mass, strength, lean body mass and bone density that it far exceeds the advantage of a few centimetres in arm length.

No magic bullet, no one-size-fits-all policy can satisfy all sides. The issue involves competing rights and strong emotions. Worryingly a recent UK Sports Councils Equality Group report also found that women in sport were told to keep quiet by their national governing bodies and feared abuse on social media if they voiced their opinions.

Yet perhaps times are changing. At the Sport Resolutions dispute resolution service last week several experts were able to discuss openly and courteously what sports should do next. It made for fascinating listening. For David Grevemberg, of the Centre for Sport and Human Rights, inclusion mattered most. And if sport had to radically change, then it should. Are there ways, that are not infringing on human rights, to create a level playing field? he asked. Are there other conditions that we can create for example staggered starts in the 100m? Or delayed starts?

Thank you for your feedback.

Meanwhile Joanna Harper, a visiting fellow at Loughborough University and a trans woman, argued for a similar approach to the IOCs 2015 guidance but with trans women required to reduce their testosterone to below five nmol/L for at least 12 months. She said the advantages were small enough that trans women and cis women can have equitable and meaningful sport.

However, for Dr Nicola Williams, a spokeswoman for Fair Play For Women, the best solution would be for men to budge up and be more inclusive by allowing trans women and trans men into an open or universal category, with a separate category exclusively preserved for natal females.

Whatever your view, one thing is clear: this issue is not going away. And Thomass groundbreaking performances have only made that clearer to Richard Budgett, the IOC and the rest of us.

Here is the original post:
Sports trans issue is here to stay. But at last, the debate is starting to change - The Guardian

Go here for Part One.

Content Warning: This post contains discussions of medical and sexual abuse of children. Please read with caution.

Dr. John Money was a psychologist and researcher at Johns Hopkins. He did a lot of research into gender and sex, both medically and sociologically, and invented a number of terms and ideas we now associate with both. However, his reputation is not, as the saying goes, great. He was involved with a number of experiments in performing gender-related surgeries on infants, the most infamous being the case of David Reimer.

David Reimer, date unknown

Reimer was born in 1965, one of a pair of twin boys. A botched circumcision destroyed his penis as an infant. Money spent decades championing the idea that gender identity is primarily learned. He persuaded Reimers parents that it would be better for him to receive further surgeries and be raised as a girl (Brenda). They did so. And Moneys involvement didnt stop there. During subsequent appointments with the twins, he forced them to strip for genital inspections (sometimes taking pictures) and to engage in sexual play, claiming that such childhood rehearsals were essential to develop a healthy adult gender identity.1 He trumpeted what he called the John/Joan case as proof positive of his theories about gender being more a result of nurture than nature.

Unfortunately for the victims of this disgusting quack, he was wrong. By age eleven, Brenda had a strong sense he was not a girl, despite regular estrogen injections and female puberty. Finally, in 1980, the Reimers told Brenda the truth. He promptly took on a male identity (including the name David) and began to receive testosterone injections and masculinizing surgeries. No amount of female socialization or hormone replacement therapy had been able to efface his inner sense of who he was.2

Now, I expect a lot of anti-trans readers (Catholic or not) will be nodding along sagely to all of this. You cant fight nature. You cant just decide to be a different gender. Try, and it will take a terrible toll, perhaps a deadly one. This is why all this gender ideology stuff is so dangerous.

But is that really the lesson here? Because if it were that simple, gender transition should produce far greater misery than the dysphoria its meant to treat. But thats not what the evidence shows: on the contrary, transition is the only recognized treatment for adult dysphoria in modern medicine.3 Opponents of gender ideology love to cite detransitioners (people who transitioned to another gender and later changed their minds) as evidence that transition is bad and dangerous, but if anything, they prove the opposite.4 Only a tiny percentage of people whove transitioned pursue detransition, and of those, an even smaller fraction claim to do so out of regret. Most cite factors like prohibitive medical expenses and family rejectionnot a keen inner sense that they were and remain their old gender.

The actual experiences of trans people line up far more with David Reimers than with the lives of cisgender5 people. Theyre usually raised and socialized according to their birth sex; most experience all the normal hormonal changes of puberty. Yet none of this effaces the sense, which they often have from an even earlier age than Reimer, that their gender is not the same as their physical sex. Could any serious person claim that these peoples minds have been changed by a fad? When both nurture and nature have been working to settle them since infancy?

And whats even more ridiculous about all this is, we just did this. We spent the 1980s, 1990s, and 2000s trying out the whole ex-gay narrative. And in 2013, the largest ex-gay organization in the world shut its doors and its leader issued a public apology for the harm hed done.

Does it follow that transgender issues are just like homosexuality? No. But can we at least not rush to make all the same assumptionsthat being trans is a psychological disorder, that its the parents fault for not nurturing the child right, that its curable with the right therapy, that people are doing it for attentionthat just gave us such a colossal series of embarrassing disasters? Can we please stop for five damn minutes and actually look at the research thats been done about this, instead of pretending we must have the answers already because the Church is infallible?

Its no insult to the Church to suggest that she hasnt yet answered a question that simply hadnt been raised before. And its no compliment to suppose that she is incapable of handling new questions. The modern concept of being transgender has antecedents in cultures all over the world, yes. But as far as I can tell, it hasnt been posed in exactly this form before, or with the same scientific resources to help answer it we have today.

Worse still, were not even done with Money. Because he didnt start his career of experimenting on the bodies of helpless infants in 1965. His career goes further back, and gets into the correction of the bodies of intersex people.

And whats intersexuality? I am, both sarcastically and sincerely, glad you asked.

Part Three to come.

1I expect it will come as no surprise to anyone that, while allowing that it could be sadistic, Dr. Money considered affectional pedophilia to be perfectly healthy as well.

2Reimers life, I am sorry to say, remained tragic. He continued to struggle with mental problems throughout his life, as did his brother, who died of an overdose in 2002. In 2004, at age 38, Reimer took his own life. The twins parents consider Dr. Money responsible for both deaths; he himself died in 2006.

3I specify adult here, because gender dysphoria in children does seem to weaken or fade completely at puberty in some cases. However, the research on this is stillno pun intendedin its infancy. It is also true that some adults choose to manage dysphoria, rather than treating it through transition; this doesnt change the fact that managing a condition isnt the same as treating it.

4More realistically, they prove neither: studies of detransition are few as yet, and many have small sample sizes that limit their usefulness.

5Cisgender means a person who identifies with the gender of their birth sex.

Read more here:
With My Body, I Thee Worship: Part Two - Patheos

2. An J, Cheetham TC, Van Den Eeden S. PS336: testosterone replacement therapy patterns for aging males in a managed care setting. Clin Med Res. 2013;11(3):141.

3. Carnegie C. Diagnosis of hypogonadism: clinical assessments and laboratory tests. Rev Urol. 2004;6(suppl 6):S3S8.

4. Seftel A. Male hypogonadism. Part II: etiology, pathophysiology, and diagnosis. Int J Impot Res. 2006;18(3):223228.

5. Kalyani RR, Gavini S, Dobs AS. Male hypogonadism in systemic disease. Endocrinol Metab Clin North Am. 2007;36(2):333348.

6. Zarotsky V, Huang MY, Carman W, et al. Systematic literature review of the epidemiology of nongenetic forms of hypogonadism in adult males. J Hormones. 2014. http://dx.doi.org/10.1155/2014/190347. Accessed March 3, 2017.

7. Smith HS, Elliott JA. Opioid-induced androgen deficiency (OPIAD). Pain Physician. 2012;15(3 suppl):ES145ES156.

8. Basaria S. Male hypogonadism. Lancet. 2014;383(9924):12501263.

9. Bhasin S, Cunningham GR, Hayes FJ, et al.; Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):25362559.

10. Emmelot-Vonk MH, Verhaar HJ, Nakhai-Pour HR, Grobbee DE, van der Schouw YT. Low testosterone concentrations and the symptoms of testosterone deficiency according to the Androgen Deficiency in Ageing Males (ADAM) and Ageing Males' Symptoms rating scale (AMS) questionnaires. Clin Endocrinol (Oxf). 2011;74(4):488494.

11. Morales A, Bebb RA, Manjoo P, et al.; Canadian Men's Health Foundation Multidisciplinary Guidelines Task Force on Testosterone Deficiency. Diagnosis and management of testosterone deficiency syndrome in men: clinical practice guideline. CMAJ. 2015;187(18):13691377.

12. Huo S, Scialli AR, McGarvey S, et al. Treatment of men for low testosterone: a systematic review. PLoS One. 2016;11(9):e0162480.

13. Boloa ER, Uraga MV, Haddad RM, et al. Testosterone use in men with sexual dysfunction: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc. 2007;82(1):2028.

14. Snyder PJ, Bhasin S, Cunningham GR, et al.; Testosterone Trials Investigators. Effects of testosterone treatment in older men. N Engl J Med. 2016;374(7):611624.

15. Giltay EJ, Tishova YA, Mskhalaya GJ, Gooren LJ, Saad F, Kalinchenko SY. Effects of testosterone supplementation on depressive symptoms and sexual dysfunction in hypogonadal men with the metabolic syndrome. J Sex Med. 2010;7(7):25722582.

16. Jones TH, Arver S, Behre HM, et al.; TIMES2 Investigators. Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care. 2011;34(4):828837.

17. Gianatti E, Dupuis P, Hoermann R, Zajac JD, Grossmann M. Effect of testosterone treatment on constitutional and sexual symptoms in men with type 2 diabetes in a randomized, placebo-controlled clinical trial. J Clin Endocrinol Metab. 2014;99(10):38213828.

18. Alhathal N, Elshal AM, Carrier S. Synergetic effect of testosterone and phophodiesterase-5 inhibitors in hypogonadal men with erectile dysfunction: a systematic review. Can Urol Assoc J. 2012;6(4):269274.

19. Buvat J, Montorsi F, Maggi M, et al. Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST study). J Sex Med. 2011;8(1):284293.

20. American Urological Association: ten things physicians and patients should question. February 21, 2013. http://www.choosingwisely.org/societies/american-urological-association/. Accessed September 5, 2016.

21. Fink HA, Ewing SK, Ensrud KE, et al. Association of testosterone and estradiol deficiency with osteoporosis and rapid bone loss in older men. J Clin Endocrinol Metab. 2006;91(10):39083915.

22. Isidori AM, Giannetta E, Greco EA, et al. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf). 2005;63(3):280293.

23. Kenny AM, Kleppinger A, Annis K, et al. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. J Am Geriatric Society. 2010;58(6):11341143.

24. Snyder PJ, Kopperdahl DL, Stephens-Shields AJ, et al. Effect of testosterone treatment on volumetric bone density and strength in older men with low testosterone: a controlled clinical trial JAMA Intern Med. 2017;177(4):471479.

25. Hildreth KL, Barry DW, Moreau KL, et al. Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels. J Clin Endocrinol Metab. 2013; 98(5): 18911900.

26. Srinivas-Shankar U, Roberts SA, Connolly MJ, et al. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2010; 95(2):639650.

27. Travison T, Basaria S, Storer T, et al. Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation. J Gerontol A Biol Sci Med Sci. 2011;66(10):10901099.

28. Fleurence R, Williamson R, Jing Y, et al. A systematic review of augmentation strategies for patients with major depressive disorder. Psychopharmacol Bull. 2009;42(3):5790.

29. Shamlian NT, Cole MG. Androgen treatment of depressive symptoms in older men: a systematic review of feasibility and effectiveness. Can J Psychiatry. 2006;51(5):295299.

30. Zarrouf FA, Artz S, Griffith J, Sirbu C, Kommor M. Testosterone and depression: systematic review and meta-analysis. J Psychiatr Pract. 2009; 15(4):289305.

31. Pope HG Jr, Amiaz R, Brennan BP, et al. Parallel-group placebo-controlled trial of testosterone gel in men with major depressive disorder displaying an incomplete response to standard antidepressant treatment. J Clin Psychopharmacol. 2010;30(2):126134.

32. Lu PH, Masterman DA, Mulnard R, et al. Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and healthy elderly men. Arch Neurol. 2006;63(2):177185.

33. Kenny AM, Bellantonio S, Gruman CA, Acosta RD, Prestwood KM. Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci. 2002;57(5):M321M325.

34. Huang G, Wharton W, Bhasin S, et al. Effects of long-term testosterone administration on cognition in older men with low and low-to-normal testosterone concentrations: a prespecified secondary analysis of data from the randomised, double-blind, placebo-controlled TEAAM trial. Lancet Diabetes Endocrinol. 2016;4(8):657665.

35. Tong SF, Ng CJ, Lee BC, et al. Effect of long-acting testosterone undecanoate treatment on quality of life in men with testosterone deficiency syndrome: a double blind randomized controlled trial. Asian J Androl. 2012;14(4):604611.

36. Hackett G, Cole N, Bhartia M, Kennedy D, Raju J, Wilkinson P. Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-of-life parameters vs. placebo in a population of men with type 2 diabetes. J Sex Med. 2013;10(6): 16121627.

37. Basaria S, Harman SM, Travison TG, et al. Effects of testosterone administration for 3 years on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels: a randomized clinical trial. JAMA. 2015;314(6):57081.

38. U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA cautions about using testosterone products for low testosterone due to aging; requires labeling change to inform of possible increased risk of heart attack and stroke with use. March 3, 2015. http://www.fda.gov/Drugs/DrugSafety/ucm436259.htm. Accessed March 12, 2015.

39. Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014;9(1):e85805.

40. Vigen R, O'Donnell CI, Barn AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels [published correction appears in JAMA. 2014; 311(9):967]. JAMA. 2013;310(17):18291836.

41. Xu L, Freeman G, Cowling BJ, Schooling CM. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med. 2013;11:108.

42. Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363(2):109122.

43. Haddad RM, Kennedy CC, Caples SM, et al. Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc. 2007;82(1):2939.

44. Corona G, Maseroli E, Rastrelli G, et al. Cardiovascular risk associated with testosterone boosting medications: a systematic review and meta-analysis. Exp Opin Drug Saf. 2014;13(10):13271351.

45. Sharma R, Oni OA, Gupta K, et al. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J. 2015;36(40):27062715.

46. Baillargeon J, Urgan RJ, Kuo YF, et al. Risk of myocardial infarction in older men receiving testosterone therapy. Ann Pharmacother. 2014; 48(9): 11381144.

47. Shores MM, Smith NL, Forsberg CW, Anawalt BD, Matsumoto AM. Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metab. 2012;97(6):20502058.

48. Muraleedharan V, Marsh H, Kapoor D, Channer KS, Jones TH. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Eur J Endocrinology. 2013;169(6):725733.

49. Morgentaler A, Miner MM, Caliber M, Guay AT, Khera M, Traish AM. Testosterone therapy and cardiovascular risk: advances and controversies. Mayo Clin Proc. 2015;90(2):224251.

50. Calof OM, Singh AB, Lee ML, et al. Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci. 2005; 60(11):14511457.

51. Fernndez-Balsells MM, Murad MH, Lane M, et al. Clinical review 1: adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2010;95(6):25602575.

52. Kang DY, Li HJ. The effect of testosterone replacement therapy on prostate-specific antigen (PSA) levels in men being treated for hypogonadism: a systematic review and meta-analysis. Medicine (Baltimore). 2015;94(3):e410.

53. Gray H, Seltzer J, Talbert RL. Recurrence of prostate cancer in patients receiving testosterone supplementation for hypogonadism. Am J Health Syst Pharm. 2015;72(7):536541.

54. Kohn TP, Mata DA, Ramasamy R, Lipshultz LI. Effects of testosterone replacement therapy on lower urinary tract symptoms: a systematic review and meta-analysis. Eur Urol. 2016;69(6):10831090.

55. Roy CN, Snyder PJ, Stephens-Shields AJ, et al. Association of testosterone levels with anemia in older men: a controlled clinical trial. JAMA Intern Med. 2017;177(4):480490.

56. U.S. Food and Drug Administration. FDA adding general warning to testosterone products about potential for venous blood clots. June 19, 2014. http://www.fda.gov/Drugs/DrugSafety/ucm401746.htm. Accessed March 12, 2016.

57. Baillargeon J, Urban RJ, Morgentaler A, et al. Risk of venous thromboembolism in men receiving testosterone therapy. Mayo Clin Proc. 2015; 90(8):10381045.

58. Sharma R, Oni OA, Chen G, et al. Association between testosterone replacement therapy and the incidence of DVT and pulmonary embolism: a retrospective cohort study of the Veterans Administration database. Chest. 2016;150(3):563571.

59. The use of testosterone and the aging male. Pharmacist's Letter/Prescriber's Letter. October 2015. http://pharmacistsletter.therapeuticresearch.com/pl/Browse.aspx?cs=amp;&s=PLamp;&pt=2amp;&fpt=31amp;&dd=320411&pb=PLamp;&cat=3658amp;&segment=9574 (login required). Accessed February 10, 2015.

60. Lexicomp Online. http://online.lexi.com/action/home (login required). Accessed March 20, 2016.

61. U.S. Preventive Services Task Force. Prostate cancer screening. May 2012. http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/prostate-cancer-screening. Accessed March 14, 2017.

62. Burger HG. Androgen production in women. Fertil Steril. 2002;77 (suppl 4):S3S5.

63. Simpson ER. Aromatization of androgens in women: current concepts and findings. Fertil Steril. 2002;77(suppl 4):S6S10.

64. Elraiyah T, Sonbol M, Wang Z, et al. Clinical review: the benefits and harms of systemic testosterone therapy in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2014;99(10):35433550.

65. Wierman ME, Arlt W, Basson R, et al. Androgen therapy in women: a reappraisal: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(10):34893510.

66. Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an endocrine society clinical practice guidelines. J Clin Endocrinol Metab. 2017;102(11):38693903.

67. Margo K, Winn R. Testosterone treatments: why, when, and how? Am Fam Physician. 2006;73(9):15911598.

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Testosterone Therapy: Review of Clinical Applications ...

Testosterone replacement improves quality of life and is aromatized in men in adipose tissues to estrogen. Hyperestrogenism is believed to be harmful to male sexuality. This is a description of our experience of screening 34,016 men in the Low T Centers, of which approximately 50% were converted to treatment. Men were treated with injectable testosterone, and we have available data from 2009 to 2014. The data were extracted from our electronic health record (AdvancedMD) of 35 Low T Centers across the United States. In all, 7,215 (20.2%) out of the 34,016 patients had high estradiol levels defined as 42.6 pg/ml. Estradiol was measured using electro-chemiluminescence immunoassay. Of the patients who had high estradiol levels, the age distribution was as follows: 132/989 (13.3%) were older than 65 years, 3,753/16,955 (22.1%) were between 45 and 65 years; 2,968/15,857 (18.7%) were between 25 and 44 years, 7/215 (3.3%) were younger than 25 years. The difference between extreme age groups (<25 and 65) was statistically significant using a chi-square test (p = .013). The correlation coefficient of serum estradiol to age was .53, SD = 8.21. It was observed that practitioners used aromatase inhibitor and selective estrogen receptor modulator to treat symptoms of hyperestrogenism, irrespective of blood estradiol levels. Gynecomastia was rarely documented as a reason for the prescription. Our finding was that high estradiol levels were not associated with higher rates of low libido but established higher rates of documented low libido with those with normal or lower estradiol levels. The difference was statistically significant (p < .05).

Keywords: age; aromatase inhibitor/SERM; estrogen; gynecomastia; testosterone therapy.

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High estrogen in men after injectable testosterone therapy ...

Testosterone

Testosterone is a male steroid hormone that does a lot more for men than just promote a healthy sex drive. The hormone affects several other factors in your health, including body fat, muscle mass, bone density, red blood cell count, and mood.

Normal testosterone levels are between 300 and 1,000 ng/dL. If a blood test shows that your levels are far below the norm, your doctor may suggest testosterone injections. These are a form treatment called testosterone replacement therapy.

Testosterone injections are most often given by your doctor. The injection site is typically in the gluteal muscles in the buttocks. However, your doctor may allow you to self-administer the injections. In that case, the injection site would be in your thigh muscles.

Men naturally start losing some of their testosterone when they hit their 30s or 40s. A more rapid decline in testosterone levels may indicate a problem called low testosterone (low T). Common symptoms of low T include:

Some men may also have changes in the size of their penis and testicles. Others may have breast swelling.

Some men may want to diagnose themselves with low T. The problem with self-diagnosis is that many of the symptoms of low T are normal parts of aging, so using them for diagnosis isnt reliable. A doctor-ordered testosterone level test is the only way to find out if your testosterone levels are too low.

When you see your doctor, they will take a thorough health history and do a physical exam. In addition to a blood test to measure your testosterone levels, youll also likely have a test that measures your red blood cell count. Testosterone injections can increase your red blood cell count, so this test is done to make sure you arent at risk of a dangerous increase in these cells.

If your exam and tests reveal that you have low T, your doctor may suggest testosterone injections.

The purpose of testosterone injections is to help regulate male hormone levels to help address problems related to low T. For men with low T, the benefits of these injections can include:

Men generally have less body fat than women. This is partly related to testosterone, which regulates fat distribution and muscle maintenance in your body. With low T, youll likely notice an increase in body fat, especially around your midsection.

Your hormones also help regulate muscle growth. So, with low T, you may feel like youre losing muscle size or strength. However, this only occurs if your low T is prolonged and severe.

Testosterone shots can help regulate fat distribution, but you shouldnt expect significant weight changes from hormone therapy alone. As for muscle maintenance, testosterone therapy has been found to help increase muscle mass, but not strength.

Low sperm count is a common side effect of low T. This problem can make it difficult if you and your partner are trying to get pregnant. However, if low T is to blame for problems with conception, dont count on testosterone injections to help. Testosterone therapy can itself lead to reduced sperm counts, especially at high doses.

According to GoodRx.com, the cost of 1 mL (200 mg/mL) of Depo-Testosterone is about $30. The same amount of testosterone cypionate, the generic version of that drug, runs about $12$26. The Depo-Testosterone label states that shots should be given every two to four weeks. Considering that dosage varies by patient, the cost could run anywhere from less than $24 per month to more than $120 per month.

These estimates only cover the drug itself, and not all possible costs of treatment. For instance, if you receive the injections from your doctor, theres a cost for the office visits. This is in addition to the cost of office visits for monitoring, as your doctor will likely monitor your condition carefully to check for side effects and to make sure the injections are working properly. If you give yourself the injections, you may also need to buy needles and syringes.

Testosterone therapy doesnt cure the cause of low T, it just raises testosterone levels up to a normal range. Therefore, injections could be a lifelong treatment if you continue to need them.

Some insurance companies cover portions of the costs, but youll want to check your coverage in advance. If you have questions about the costs, talk to your doctor.

Testosterone shots can help many men with low T. Still, this doesnt mean that these powerful injections are safe for all men. Be sure to tell your doctor about all health conditions you have before starting testosterone therapy.

You will likely need extra monitoring from your doctor if you have heart disease, sleep apnea, or a high red blood cell count. And you should not use testosterone injections at all if you have breast cancer or prostate cancer.

Testosterone shots may also increase your risk of certain health problems, such as:

Testosterone injections can be helpful, but only if you actually have low T. If youre wondering if these injections might be right for you, talk to your doctor. They can test you for low T. If they diagnose you, you can discuss whether these injections would be a good choice for you.

If you dont end up having low T but still feel like your hormone levels might be off, keep in mind that good nutrition, regular exercise, and avoiding smoking could help you feel better. If those dont help, be sure to talk to your doctor.

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Testosterone Injections: Are They Right for You?

Masculinizing hormone therapy, also known as transmasculine hormone therapy, or female-to-male (or FTM) hormone therapy, is a form of hormone therapy and gender affirming therapy which is used to change the secondary sexual characteristics of transgender people from feminine or androgynous to masculine. It is a common type of transgender hormone therapy (another being feminizing hormone therapy), and is predominantly used to treat transgender men and other transmasculine individuals. Some intersex people also receive this form of therapy, either starting in childhood to confirm the assigned sex or later if the assignment proves to be incorrect.

The purpose of this form of therapy is to cause the development of the secondary sex characteristics of the desired sex, such as voice deepening and a masculine pattern of hair, fat, and muscle distribution. It cannot undo many of the changes produced by naturally occurring puberty, which may necessitate surgery and other treatments to reverse. The medications used for FTM therapy include, mainly, androgens (namely testosterone) and GnRH analogues.

While the therapy cannot undo the effects of a person's first puberty, developing secondary sex characteristics associated with a different sex can relieve some or all of the distress and discomfort associated with gender dysphoria, and can help the person to "pass" or be seen as their gender. Introducing exogenous hormones into the body impacts it at every level and many patients report changes in energy levels, mood, appetite, etc. The goal of the therapy, and indeed all somatic treatments, is to provide patients with a more satisfying body that is more congruent with their gender identity.

Several contraindications to androgen therapy exist.[1] An absolute medical contraindication is pregnancy.

Relative medical contraindications are:

Hormone therapy for transmasculine individuals has not been adequately studied. Two recent studies indicate the potential for elevated risk of cardiovascular events. Nota, et al (2019) found that transgender men taking testosterone had an increased risk of cardiovascular events compared to cisgender women, with 11 vs. 3 cardiovascular events per 100,000 person-years, though the risk was less than that of cisgender men. Researchers were not able to control for smoking status or stressors.[2]Another recent study (Alzahrani, 2019) found elevated risk of heart attacks among self-identified transgender menwhich persisted even after adjusting for age, diabetes mellitus, chronic kidney disease, smoking, hypertension, hypercholesterolemia, and exercisethough the study did not include data about whether the subjects were undergoing hormone therapy and did not control for stressors. The study found that transgender men have a >4-fold and 2-fold increased odds of having a myocardial infarction when compared with cisgender women and cisgender men, respectively.[3] Since testosterone for transgender men is intended to be used over an individual's entire lifespan, the full range of risks of such lengthy testosterone administration is not yet known.

Testosterone is metabolized by the cytochrome P450 enzyme system (specifically CYP3A isoforms) in the liver. There are certain drugs that increase or decrease the activity of cytochrome P450 enzymes and may cause increased or decreased levels of testosterone:

Testosterone can also alter the effects of other drugs:

Because of these interactions, it is advised that trans men make their healthcare providers aware of their hormone therapy when this is relevant to their treatment for other medical issues.

Medications used in hormone therapy for transgender men include androgens and anabolic steroids like testosterone (by injection and other routes) to produce masculinization, suppress estrogen and progesterone levels, and prevent/reverse feminization; GnRH agonists and antagonists to suppress estrogen and progesterone levels; progestins like medroxyprogesterone acetate to suppress menses; and 5-reductase inhibitors to prevent/reverse scalp hair loss.

The elimination half-life of testosterone in the blood is about 70 minutes, so it is necessary to have a continuous supply of the hormone for masculinization.

'Depot' drug formulations are created by mixing a substance with the drug that slows its release and prolongs the action of the drug. The two primarily used forms in the United States are the testosterone esters testosterone cypionate (Depo-Testosterone) and testosterone enanthate (Delatestryl or Xyosted) which are almost interchangeable. Testosterone enanthate is purported to be slightly better with respect to even testosterone release, but this is probably more of a concern for bodybuilders who use the drugs at higher doses (2501000mg/week) than the replacement doses used by transgender men (50100mg/week). These testosterone esters are mixed with different oils, so some individuals may tolerate one better than the other. Testosterone enanthate costs more than testosterone cypionate and is more typically the one prescribed for hypogonadal males in the US. Testosterone cypionate is more popular in the US than elsewhere (especially amongst bodybuilders). Other formulations exist but are more difficult to come by in the US. A formulation of injected testosterone available in Europe and the US, testosterone undecanoate (Nebido, Aveed)[13][14] provides significantly improved testosterone delivery with far less variation outside the eugonadal range than other formulations with injections required only four times yearly. However, each quarterly dose requires an injection of 4mL of oil which may require multiple simultaneous injections. Testosterone undecanoate is also much more expensive as it is still under patent protection. Testosterone propionate is another testosterone ester that is widely available, including in the US, Canada, and Europe, but it is very short-acting compared to the other testosterone esters and must be administered once every 2 or 3days, and for this reason, is rarely used.

The adverse side effects of injected testosterone esters are generally associated with high peak levels in the first few days after an injection. Some side effects may be ameliorated by using a shorter dosing interval (weekly or every ten days instead of twice monthly with testosterone enanthate or testosterone cypionate). 100mg weekly gives a much lower peak level of testosterone than does 200mg every two weeks, while still maintaining the same total dose of androgen. This benefit must be weighed against the discomfort and inconvenience of doubling the number of injections.

Injectable forms of testosterone can cause a lung problem called pulmonary oil microembolism (POME). Symptoms of POME include cough, shortness of breath, tightening of the throat, chest pain, sweating, dizziness, and fainting.[15][16] A postmarketing analysis by the manufacturer of Aveed (testosterone undeconate injection) found that POME occurred at a rate of less than 1% per injection per year for Aveed.[17]

Injected testosterone esters should be started at a low dose and titrated upwards based on trough levels (blood levels drawn just before your next shot). A trough level of 500ng/dL is sought. (Normal range for a cisgender male is 290 to 900ng/dL).

Both testosterone patches, creams and gels are available. Both approximate normal physiological levels of testosterone better than the higher peaks associated with injection. Both can cause local skin irritation (more so with the patches).

Patches slowly diffuse testosterone through the skin and are replaced daily. The cost varies, as with all medication, from country to country, it is about $150/month in the US, and about 60 in Germany.

Transdermal testosterone is available throughout the world under the brand names Andromen Forte, Androgel, Testogel and Testim. They are absorbed quickly when applied and produce a temporary drug depot in the skin which diffuses into the circulation, peaking at 4 hours and decreasing slowly over the rest of the day. The cost varies, as with all medication, from country to country, from as little as $50/month to about $280/month.

Transdermal testosterone poses a risk of inadvertent exposure to others who come in contact with the patient's skin. This is most important for patients whose intimate partners are pregnant or those who are parents of young children as both of these groups are more vulnerable to the masculinizing effects of androgens. Case reports of significant virilization of young children after exposure to topical androgen preparations (both prescription and 'supplement' products) used by their caregivers demonstrates this very real risk.

Implants, as subcutaneous pellets, can be used to deliver testosterone (brand name Testopel). 6 to 12 pellets are inserted under the skin every three months. This must be done in a physician's office, but is a relatively minor procedure done under local anesthetic. Pellets cost about $60 each, so the cost is greater than injected testosterone when the cost of the physician visit and procedure are included. The primary advantages of Testopel are that it gives a much more constant blood level of testosterone yet requires attention only four times yearly.

Oral testosterone is provided exclusively as testosterone undecanoate. It is available in Europe and Canada, but not in the US. Once absorbed from the gastrointestinal tract, testosterone is shunted (at very high blood levels) to the liver where it can cause liver damage (albeit very rarely) and worsens some of the adverse effects of testosterone, like lower HDL cholesterol. In addition, the first-pass metabolism of the liver also may result in testosterone levels too low to provide satisfactory masculinization and suppress menses. Because of the short terminal half-life of testosterone, oral testosterone undecanoate must be administered two to four times per day, preferably with food (which improves its absorption).

In 2003, the FDA approved a buccal form of testosterone (Striant). Sublingual testosterone can also be made by some compounding pharmacies. Cost for Striant is greater than other formulations (US$180210/month). Testosterone is absorbed through the oral mucosa and avoids the first-pass metabolism in the liver which is the cause of many of the adverse effects of oral testosterone undecanoate. The lozenges can cause gum irritation, taste changes, and headache but most side effects diminish after two weeks. The lozenge is 'mucoadhesive' and must be applied twice daily.

Synthetic androgens/anabolic steroids (AAS), like nandrolone (as an ester like nandrolone decanoate or nandrolone phenylpropionate), are agonists of the androgen receptor (AR) similarly to testosterone but are not usually used in HRT for transgender men or for androgen replacement therapy (ART) in cisgender men. However, they can be used in place of testosterone with similar effects, and can have certain advantages like less or no local potentiation in so-called androgenic tissues that express 5-reductase like the skin and hair follicles (which results in a reduced rate of skin and hair-related side effects like excessive body hair growth and scalp hair loss), although this can also be disadvantageous in certain aspects of masculinization like facial hair growth and normal body hair growth). Although many AAS are not potentiated in androgenic tissues, they have similar effects to testosterone in other tissues like bone, muscle, fat, and the voice box. Also, many AAS, like nandrolone esters, are aromatized into estrogens to a greatly reduced extent relative to testosterone or not at all, and for this reason, are associated with reduced or no estrogenic effects (e.g., gynecomastia). AAS that are 17-alkylated like methyltestosterone, oxandrolone, and stanozolol are orally active but carry a high risk of liver damage, whereas AAS that are not 17-alkylated, like nandrolone esters, must be administered by intramuscular injection (via which they act as long-lasting depots similarly to testosterone esters) but have no more risk of liver damage than does testosterone.

For the sake of clarification, the term "anabolicandrogenic steroid" is essentially synonymous with "androgen" (or with "anabolic steroid"), and that natural androgens like testosterone are also AAS. These drugs all share the same core mechanism of action of acting as agonists of the AR and have similar effects, although their potency, pharmacokinetics, oral activity, ratio of anabolic to androgenic effects (due to differing capacities to be locally metabolized and potentiated by 5-reductase), capacity for aromatization (i.e., conversion into an estrogen), and potential for liver damage may all differ.

Dihydrotestosterone (DHT) (referred to as androstanolone or stanolone when used medically) can also be used in place of testosterone as an androgen. The availability of DHT is limited; it is not available in the United States or Canada, for instance, but it is available in certain European countries, including the United Kingdom, France, Spain, Belgium, Italy, and Luxembourg.[18] DHT is available in formulations including topical gel, buccal or sublingual tablets, and as esters in oil for intramuscular injection.[19] Relative to testosterone, and similarly to many synthetic AAS, DHT has the potential advantages of not being locally potentiated in so-called androgenic tissues that express 5-reductase (as DHT is already 5-reduced) and of not being aromatized into an estrogen (it is not a substrate for aromatase).

In all people, the hypothalamus releases gonadotropin-releasing hormone (GnRH) to stimulate the pituitary to produce luteinizing hormone (LH) and follicle-stimulating hormone (FSH) which in turn cause the gonads to produce sex steroids. In adolescents of either sex with relevant indicators, GnRH analogues, such as leuprorelin can be used to suspend the advance of sex steroid induced, inappropriate pubertal changes for a period without inducing any changes in the gender-appropriate direction. GnRH analogues work by initially overstimulating the pituitary gland then rapidly desensitizing it to the effects of GnRH. Over a period of weeks, gonadal androgen production is greatly reduced. There is considerable controversy over the earliest age, and for how long it is clinically, morally and legally safe to do this. The Harry Benjamin International Gender Dysphoria Association Standards of Care permits treatment from Tanner stage 2, but do not allow the addition of gender-appropriate hormones until 16, which could be five or more years. The sex steroids do have important other functions. The high cost of GnRH analogues is often a significant factor.

Antiestrogens (or so-called "estrogen blockers") like aromatase inhibitors (AIs) (e.g., anastrozole) or selective estrogen receptor modulators (SERMs) (e.g., tamoxifen) can be used to reduce the effects of high levels of endogenous estrogen (e.g., breast development, feminine fat distribution) in transgender men. In addition, in those who have not yet undergone or completed epiphyseal closure (which occurs during adolescence and is mediated by estrogen), antiestrogens can prevent hip widening as well as increase final height (estrogen limits height by causing the epiphyses to fuse).

5-Reductase inhibitors like finasteride and dutasteride can be used to slow or prevent scalp hair loss and excessive body hair growth in transgender men taking testosterone.[20] However, they may also slow or reduce certain aspects of masculinization, such as facial hair growth, normal male-pattern body hair growth, and possibly clitoral enlargement.[20][21] A potential solution is to start taking a 5-reductase inhibitor after these desired aspects of masculinization have been well-established.[20]

Progestogens can be used to control menstruation in transgender men. Depot medroxyprogesterone acetate (DMPA) may be injected every three months just as it is used for contraception. Generally after the first cycle, menses are greatly reduced or eliminated. This may be useful for transgender men prior to initiation of testosterone therapy.

In those who have not yet started or completed epiphyseal closure, growth hormone can be administered, potentially in conjunction with an aromatase inhibitor or a GnRH analogue, to increase final height.

The main effects of HRT of the FTM type are as follows:[22]

Many transgender men are unable to pass as cisgender men without hormones. The most commonly cited reason for this is that their voice may reveal them.

Facial changes develop gradually over time, and sexual dimorphism (physical difference between the sexes) tends to increase with age. Within a population of similar body size and ethnicity:

Frequently the first sign of endometrial cancer is bleeding in post-menopausal women. Transgender men who have any bleeding after the cessation of menses with androgen therapy should be evaluated for age appropriate causes of abnormal uterine bleeding as per cisgender female guidelines.[23]

A number of skeletal and cartilaginous changes take place after the onset of puberty at various rates and times. Sometime in the late teen years epiphyseal closure (in other words, the ends of bones are fused closed) takes place and the length of bones is fixed for life. Consequently, total height and the length of arms, legs, hands, and feet are not affected by HRT. However, details of bone shape change throughout life, bones becoming heavier and more deeply sculptured under the influence of testosterone. Many of these differences are described in the Desmond Morris book Manwatching.

The psychological changes are harder to define, since HRT is usually the first physical action that takes place when transitioning. This fact alone has a significant psychological impact, which is hard to distinguish from hormonally induced changes. Most trans men report an increase of energy and an increased sex drive. Many also report feeling more confident.

While a high level of testosterone is often associated[how?] with an increase in aggression, this is not a noticeable effect in most trans men. HRT doses of testosterone are much lower than the typical doses taken by steroid-using athletes, and create testosterone levels comparable to those of most cisgender men. These levels of testosterone have not been proven to cause more aggression than comparable levels of estrogen.

Some transgender men report mood swings, increased anger, and increased aggressiveness after starting androgen therapy. Studies are limited and small scale, however, based on self reporting over a short period of time (7 months). In a study by Motta et al, trans men also reported better anger control.[26] Many transgender men, however, report improved mood, decreased emotional lability, and a lessening of anger and aggression.[citation needed]

During HRT, especially in the early stages of treatment, blood tests should be consistently done to assess hormone levels and liver function.

Gianna Israel and colleagues have suggested that for pre-oophorectomy trans men, therapeutic testosterone levels should optimally fall within the normal male range, whereas estrogen levels should optimally fall within the normal female range. Before oophorectomy, it is difficult and frequently impractical to fully suppress estrogen levels into the normal male range, especially with exogenous testosterone aromatizing into estrogen, hence why the female ranges are referenced instead. In post-oophorectomy trans men, Israel and colleagues recommend that both testosterone and estrogen levels fall exactly within the normal male ranges. See the table below for all of the precise values they suggest.[31]

The optimal ranges listed for testosterone only apply to individuals taking bioidentical hormones in the form of testosterone (including esters) and do not apply to those taking synthetic AAS (e.g., nandrolone) or dihydrotestosterone.

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Masculinizing hormone therapy - Wikipedia

OverviewWhat is low testosterone (male hypogonadism)?

Low testosterone (male hypogonadism) is a condition in which the testes (testicles, the male reproductive glands) do not produce enough testosterone (a male sex hormone).

In men, testosterone helps maintain and develop:

Low testosterone affects almost 40% of men aged 45 and older. It is difficult to define normal testosterone levels, because levels vary throughout the day and are affected by body mass index (BMI), nutrition, alcohol consumption, certain medications, age and illness.

As a man ages, the amount of testosterone in his body gradually drops. This natural decline starts after age 30 and continues (about 1% per year) throughout his life.

There are many other potential causes of low testosterone, including the following:

Symptoms of low testosterone depend on the age of person, and include the following:

Other changes that occur with low testosterone include:

Low testosterone is diagnosed by measuring the amount of testosterone in the blood with a blood test. It may take several measurements to determine if a patient has low testosterone, since levels tend to change throughout the day. The highest levels of testosterone are generally in the morning, near 8 a.m. This is why doctors prefer to measure testosterone levels in the early morning.

Low testosterone is treated with testosterone replacement therapy, which can be given in several different ways:

(Oral testosterone is not approved for use in the United States.)

Potential benefits of testosterone replacement therapy may include:

The side effects of testosterone replacement therapy include:

Laboratory abnormalities that can occur with testosterone replacement include:

If you are taking hormone replacement therapy, regular follow-up appointments with your physician are important.

Guidelines suggest discussing the potential risk vs. benefit of evaluating prostate cancer risk and prostate monitoring. The doctor and patient will decide together regarding prostate cancer monitoring. For patients who choose monitoring, clinicians should assess prostate cancer risk before starting testosterone treatment, and 3 to 12 months after starting testosterone:

Testosterone replacement therapy may cause the prostate to grow. If a man has early prostate cancer, there is concern that testosterone may stimulate the cancer's growth. Therefore, men who have prostate cancer should not take testosterone replacement therapy. It is important for all men considering testosterone replacement therapy to undergo prostate screening before starting this therapy.

Other men who should not take testosterone replacement therapy include those who have:

There are no known ways to prevent low testosterone that is caused by genetic conditions or damage to the testes or pituitary gland.

A healthy lifestyle that includes good nutrition, exercise, weight management, and that avoids excessive use of alcohol and drugs can help keep testosterone levels normal.

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Low Testosterone (Low T): Causes, Symptoms, Diagnosis ...