Significant decrease in testosterone therapy since 2013

Testosterone Prescribing in the United States, 2002-2016

Testosterone use in the United States tripled from 2001 through 2011, mostly in men without a clear indication.

In late 2013 and early 2014, two studies reported increased myocardial infarction and stroke associated with testosterone use.

The US Food and Drug Administration (FDA) issued a safety bulletin on January 31, 2014.

After a decade of growth, the percentage of US men receiving testosterone prescriptions decreased from 2013,  falling to less than 2% of men by 2016.

This prescribing trends study was published July 10, 2018.

The key role of androgen in male sex maintenance

Blockage of androgen and administration of estrogen induce transdifferentiation of testis into ovary

2017 Study Abstract

Induction of sex reversal of XY fish has been restricted to the sex undifferentiated period.

In the present study, differentiated XY tilapia were treated with trilostane (TR), metopirone (MN) and glycyrrhetinic acid (GA) (inhibitor of 3β-HSD, Cyp11b2 and 11β-HSD, respectively) alone or in combination with 17β-estradiol (E2) from 30 to 90 dah (days after hatching). At 180 dah, E2 alone resulted in 8.3%, and TR, MN and GA alone resulted in no secondary sex reversal (SSR), whereas TR + E2, MN + E2 and GA + E2 resulted in 88.3, 60.0 and 46.7% of SSR, respectively.

This sex reversal could be rescued by simultaneous administration of 11-ketotestosterone (11-KT). Compared with the control XY fish, decreased serum 11-KT and increased E2 level were detected in SSR fish. Immunohistochemistry analyses revealed that Cyp19a1a, Cyp11b2 and Dmrt1 were expressed in the gonads of GA + E2, MN + E2 and TR + E2 SSR XY fish at 90 dah, but only Cyp19a1a was expressed at 180 dah. When the treatment was applied from 60 to 120 dah, TR + E2 resulted in 3.3% of SSR, MN + E2 and GA + E2 resulted in no SSR.

These results demonstrated that once 11-KT was synthesized, it could antagonize E2-induced male-to-female SSR, which could be abolished by simultaneous treatment with the inhibitor of steroidogenic enzymes. The upper the enzyme was located in the steroidogenic pathway, the higher SSR rate was achieved when it was inhibited as some of the precursors, such as androstenedione, testosterone and 5α-dihydrotestosterone, could act as androgens. These results highlight the key role of androgen in male sex maintenance.

Image credit Rusty Clark.

Low Testosterone

Illness inflation – How everyday conditions become medical disorders

Millions may have ‘low testosterone. But critics say it is just about getting older and fatter.

Independent experts say the new definition is an example of ‘medicalization’ – turning common evolution into medical conditions that call for treatment.

Testosterone treatment and risk of venous thromboembolism

Population based case-control study, The BMJ, November 2016

Abstract

Objective
To determine the risk of venous thromboembolism associated with use of testosterone treatment in men, focusing particularly on the timing of the risk.

Design
Population based case-control study

Setting
370 general practices in UK primary care with linked hospital discharge diagnoses and in-hospital procedures and information on all cause mortality.

Testosterone treatment and risk of venous thromboembolism: population based case-control study, The BMJ 2016;355:i5968, 30 November 2016.

Participants
19 215 patients with confirmed venous thromboembolism (comprising deep venous thrombosis and pulmonary embolism) and 909 530 age matched controls from source population including more than 2.22 million men between January 2001 and May 2013.

Exposure of interest
Three mutually exclusive testosterone exposure groups were identified: current treatment, recent (but not current) treatment, and no treatment in the previous two years. Current treatment was subdivided into duration of more or less than six months.

Main outcome measure
Rate ratios of venous thromboembolism in association with current testosterone treatment compared with no treatment were estimated using conditional logistic regression and adjusted for comorbidities and all matching factors.

Results
The adjusted rate ratio of venous thromboembolism was 1.25 (95% confidence interval 0.94 to 1.66) for current versus no testosterone treatment. In the first six months of testosterone treatment, the rate ratio of venous thromboembolism was 1.63 (1.12 to 2.37), corresponding to 10.0 (1.9 to 21.6) additional venous thromboembolisms above the base rate of 15.8 per 10 000 person years. The rate ratio after more than six months’ treatment was 1.00 (0.68 to 1.47), and after treatment cessation it was 0.68 (0.43 to 1.07). Increased rate ratios within the first six months of treatment were observed in all strata: the rate ratio was 1.52 (0.94 to 2.46) for patients with pathological hypogonadism and 1.88 (1.02 to 3.45) for those without it, and 1.41 (0.82 to 2.41) for those with a known risk factor for venous thromboembolism and 1.91 (1.13 to 3.23) for those without one.

Conclusions
Starting testosterone treatment was associated with an increased risk of venous thromboembolism, which peaked within six months and declined thereafter.

Transgender Men Can Face Fighting Breast Cancer Too

The medical world has blind spots in its understanding of how to take care of trans men and women

A transgender man, is somebody who is born female, and then takes male hormones to change gender. Many transgender people switch gender without having surgery to change their body.

… ” Zil Goldstein, a nurse practitioner and program director at Mount Sinai’s transgender center, said that while she had concerns about the long-term safety of transgender hormones, she worried more about the possible harm from not prescribing them – researchers report that 41 percent of transgender people attempt suicide.” …

…  “trans men with breast cancer were often urged to stop taking testosterone. One reason is that the body converts some testosterone to estrogen, which can speed the growth of many breast tumors. And some breast cancers may also be stimulated by testosterone, … “

Very clear evidence that testosterone does not help men’s health

Treatment of Men for “Low Testosterone”: No Benefits…

A group of researchers have announced that they have established testosterone treatments benefits: none.

Abstract

Testosterone products are recommended by some prescribers in response to a diagnosis or presumption of “low testosterone” (low-T) for cardiovascular health, sexual function, muscle weakness or wasting, mood and behavior, and cognition.

We performed a systematic review of 156 eligible randomized controlled trials in which testosterone was compared to placebo for one or more of these conditions. We included studies in bibliographic databases between January 1, 1950 and April 9, 2016, and excluded studies involving bodybuilding, contraceptive effectiveness, or treatment of any condition in women or children. Studies with multiple relevant endpoints were included in all relevant tables.

Treatment of Men for “Low Testosterone”: A Systematic Review, PLOS one, September 21, 2016.

*Testosterone, Baby! marshallsegal.

Testosterone supplementation did not show consistent benefit for cardiovascular risk, sexual function, mood and behavior, or cognition. Studies that examined clinical cardiovascular endpoints have not favored testosterone therapy over placebo. Testosterone is ineffective in treating erectile dysfunction and controlled trials did not show a consistent effect on libido. Testosterone supplementation consistently increased muscle strength but did not have beneficial effects on physical function. Most studies on mood-related endpoints found no beneficial effect of testosterone treatment on personality, psychological well-being, or mood.

Researchers say there are no benefits of testosterone treatments for men, the guardian, 21 September 2016.

The prescription of testosterone supplementation for low-T for cardiovascular health, sexual function, physical function, mood, or cognitive function is without support from randomized clinical trials.

Can Phthalates Exposure in Utero affect Lifelong Physical Activity?

Avoid endocrine disruptors as much as possible, especially if you are pregnant

A common chemical found in many cosmetics and personal care products may influence our will to exercise…

Mice exposed prenatally to benzyl butyl phthalate (B.B.P.) were less likely than other mice (control group) to exercise as adults.

Male mice exposed to B.B.P. in utero had notably lower levels of testosterone – than the other animals – in young adulthood.
Exposed females similarly developed during young adulthood low estrogen levels and other reproductive system abnormalities that then produced a profound desire, it seems, to sit for most of the day…

Exposure to environmental toxins before birth might change babies’ physiology in ways that affect their interest in exercise throughout their lives.

Sources – Press Releases
  • Could Environmental Chemicals Shape Our Exercise Habits?, The Times, 2016/06/29.
  • Study: Common Chemicals Might Affect Exercise Habits, opposingviews, June 29, 2016.

Fracking Chemicals Disrupt Hormone Function

Estrogen and Androgen Receptor Activities of Hydraulic Fracturing Chemicals and Surface and Ground Water in a Drilling-Dense Region

University of Missouri researchers have discovered that an oil and natural gas drilling technique called hydraulic fracturing uses chemicals that can disrupt the body’s hormones. The researchers found that the endocrine-disrupting chemicals used in the process could interfere with a class of hormones that includes testosterone and estrogen.

Sources:
  • MU Researchers Find Fracking Chemicals Disrupt Hormone Function, MU School of Medicine, News.
  • Estrogen and Androgen Receptor Activities of Hydraulic Fracturing Chemicals and Surface and Ground Water in a Drilling-Dense Region, MU School of Medicine, Endocrinology, 2013.
  • Watch it full screen or via SlideShare.
  • Meet DES Daughter Network on SlideShare.

Prenatal exposure to progesterone suppresses reproduction in male mice

P. Sreenivasula Reddy, Harini Challa, Sainath S.B, Sep 2011

Prenatal-exposure-to-proges
DiEthylStilbestrol usage review buttress the need for adequate and rigorous research into the use of drugs in pregnancy and ensure that they do more good than harm before being introduced for consumption.

Partial recovery of reproduction by testosterone

The role of androgens in development of male reproductive organs is well documented. The role of estrogens in the development of male reproductive organs remains largely unknown; although both estrogen receptors and aromatase enzyme have been identified in the developing penis of a number of species, including humans.

Male offspring of women exposed to diethylstilbestrol during pregnancy have higher incidences of epididymal cysts, cryptorchidism, hypospadiasis, and smaller testes.

Since female hormones were routinely prescribed to treat threatened pregnancy and considering the potential implications of female hormones during prenatal period on the development of male reproductive system, the present book describes the effect of prenatal exposure to progesterone on adult male reproduction.

Significant deterioration in reproduction was observed in mice exposed to progesterone during embryonic development which includes reduction in steroidogenesis and spermatogenesis. Testosterone supplementation during post-natal period partially restored the suppressed reproduction.

More DES DiEthylStilbestrol Resources

Adult exposure to bisphenol A alters male sexual behavior

The neural circuitry underlying male sexual behavior is vulnerable to chronic adult exposure to low dose of BPA

Abstract

TheEndocrineSociety logo image
The neural circuitry underlying male sexual behavior is vulnerable to chronic adult exposure to low dose of BPA.

There are human reproduction concerns associated with extensive use of bisphenol A (BPA) – containing plastic and, in particular, the leaching of BPA into food and beverages. In this context, it remains unclear whether and how exposure to BPA interferes with the developmental organization and adult activation of male sexual behavior by testosterone.

We evaluated the developmental and adult exposure to oral BPA at doses equivalent to the no-observed-adverse-effect-level (5 mg/kg body weight per day) and tolerable daily intake (TDI) (50 μg/kg body weight per day) on mouse sexual behavior and the potential mechanisms underlying BPA effects. Adult exposure to BPA reduced sexual motivation and performance at TDI dose only.

Exposed males took longer to initiate mating and reach ejaculation despite normal olfactory chemoinvestigation. This deficiency was not restored by sexual experience and was associated with unchanged circulating levels of testosterone. By contrast, developmental exposure to BPA at TDI or no-observed-adverse-effect-level dose did not reduce sexual behavior or alter the neuroanatomical organization of the preoptic area. Disrupting the neural androgen receptor resulted in behavioral and neuroanatomical effects similar to those induced by adult exposure to TDI dose. Moreover, adult exposure of mutant males to BPA at TDI dose did not trigger additional alteration of sexual behavior, suggesting that BPA and neural androgen receptor mutation share a common mechanism of action.

This shows, for the first time, that the neural circuitry underlying male sexual behavior is vulnerable to chronic adult exposure to low dose of BPA and suggests that BPA could act in vivo as an antiandrogenic compound.

Sources and more information:

  • Adult exposure to bisphenol A alters male sexual behavior,
    INRA, 10/31/2014.
  • Vulnerability of the neural circuitry underlying sexual behavior to chronic adult exposure to oral bisphenol a in male mice, NCBI Endocrinology, PMID: PubMed 24265451, 2014 Feb;155(2):502-12. doi: 10.1210/en.2013-1639. Epub 2013 Nov 21.