Would male hormonal contraceptives affect cardiovascular risk?

Zitzmann, Michael

doi:10.4103/aja.aja_2_18

Cited by 7 publications

(7 citation statements)

References 35 publications

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“…That MHC would fulfill many of the aforementioned criteria of an ideal form of contraception and has the support of many men worldwide has leads to significant research and development in this field. Mechanistically, the goal of MHC is the reversible suppression of spermatogenesis to levels consistent with infertility via suppression of testicular Leydig and Sertoli cell function ( 23 ). Through this method, investigations undertaken over the past four decades have shown that MHC can result in suppression of spermatogenesis with subsequent prevention of pregnancy though a commercial product remains unavailable ( 24 ).…”

Section: Basis For the Hormonal Approachmentioning

confidence: 99%

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The future of male contraception: a fertile ground

Khourdaji

Zillioux

Eisenfrats³

et al. 2018

Transl. Androl. Urol.

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The continued and rapid expansion of the Earth’s population mandates the need for safe and effective measures of contraception. While a plethora of options exist for women, methods of contraception for the male partner are limited to condoms and vasectomy. The sequela of this discrepancy has led to the family planning burden falling disproportionately on the female partner. For the past several decades, extensive research has been undertaken exploring the feasibility of hormonal male contraception. This proposed method of contraception has focused on suppressing spermatogenesis by exploiting the hypothalamic-pituitary-gonadal (HPG) axis. Beginning with proof of concept studies in the early nineties, administration of testosterone in healthy male subjects has been shown to be an efficacious method of inducing sterility. Owing to ethnic differences in spermatogenesis suppression and the comparatively low rate of azoospermia in Caucasian men with androgen-only regimens, investigators have explored the addition of progestins to further enhance the efficacy of hormonal contraception. Though studies have revealed promise with androgen-progestin regimens, the lack of long-term studies has precluded the development of a marketable product. Recently, more research has been directed towards identifying non-hormonal alternatives to male contraception. These non-hormonal options have ranged from the development of devices facilitating reversible occlusion of the vas deferens lumen to medications disrupting various pathways in the process of spermatogenesis. Underlying the development of hormonal and non-hormonal strategies is the shared enthusiasm men and women have towards these male directed methods. The willingness of couples to pursue these alternatives combined with the global need to reduce the psychological and socioeconomic implications of unintended pregnancy ensures that research will continue to bring this goal to fruition.

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Section: Basis For the Hormonal Approachmentioning

confidence: 99%

“…However, more randomized-control trials are necessary to determine the full adverse profile of MHC. Moreover, the relatively short length of all the trials to date precludes an adequate assessment of cardiovascular or thromboembolic events related to use ( 23 ).…”

Section: Male Hormonal Contraceptionmentioning

confidence: 99%

The future of male contraception: a fertile ground

Khourdaji

Zillioux

Eisenfrats³

et al. 2018

Transl. Androl. Urol.

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“…Questions have been raised regarding the potential metabolic effects of androgen‐progestin combinations used in male hormonal contraception studies and the potential for long‐term consequences on cardiovascular health, 7 including the development of the metabolic syndrome (insulin resistance, hypertension, dyslipidemia, central obesity) or type 2 diabetes 8,9 . Testosterone replacement therapy in hypogonadal men has been shown in some studies to improve insulin sensitivity; the effects of testosterone on metabolic syndrome and type 2 diabetes in men are less consistent 10‐12 .…”

Section: Introductionmentioning

confidence: 99%

Comparison of metabolic effects of the progestational androgens dimethandrolone undecanoate and 11β‐MNTDC in healthy men

et al. 2021

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Background: Dimethandrolone (DMA) and 11β-methyl-19-nortestosterone (11β-MNT) are two novel compounds with both androgenic and progestational activity that are under investigation as potential male hormonal contraceptives. Their metabolic effects have never been compared in men.Objective: Assess for changes in insulin sensitivity and adiponectin and compare the metabolic effects of these two novel androgens. Materials/Methods:In two clinical trials of DMA undecanoate (DMAU) and 11β-MNT dodecylcarbonate (11β-MNTDC), oral prodrugs of DMA and 11β-MNT, healthy men received drug, or placebo for 28 days. Insulin and adiponectin assays were performed on stored samples. Mixed model analyses were performed to compare the effects of the two drugs. Student's t test, or the non-parametric Kruskal-Wallis test as appropriate, was used to evaluate for an effect of active drug versus placebo.Results: Class effects were seen, with decrease in HDL-C and SHBG, and increase in weight and hematocrit, with no statistically significant differences between the two compounds. No changes in fasting glucose, fasting insulin, or HOMA-IR were seen with either compound. There was a slight decrease in adiponectin with DMAU that was not seen with 11β-MNTDC. An increase in LDL-C was seen with 11β-MNTDC but not with DMAU.Discussion: There were no significant changes in insulin resistance after 28 days of oral administration of these novel androgens despite a mild increase in weight. There may be subtle differences in their metabolic impacts that should be explored in future studies. Conclusion:Changes in metabolic parameters should be carefully monitored when investigating androgenic compounds.

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“…For example, Zitzmann reviews some of the data on the potential cardiovascular effects of male hormonal contraceptive regimens that are under development. 8 Finally, An and Gu remind us in their commentary that more studies on the safety of testosterone therapy must be done in Asia, the site of the largest population of men in the world. 9 …”

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confidence: 99%

Conclusions about testosterone therapy and cardiovascular risk

Anawalt

Yeap

2018

Asian J Androl

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In this issue of Asian Journal of Andrology (AJA), several experts have reviewed the latest data on the potential and known effects of endogenous and exogenous testosterone (T) on cardiovascular risk. In the review by Meyer and Wittert, low endogenous serum T appears to be associated with higher risk of cardiovascular disease and overall mortality in certain populations such as Klinefelter syndrome and older men, but not in men with congenital hypogonadotropic hypogonadism.1 Whether this association is causal or whether low serum testosterone is a marker of other risk factors for cardiovascular disease such as obesity, diabetes mellitus, or other systemic disease is unknown. In Yeap's review of the relationship between circulating endogenous testosterone and its major metabolites, dihydrotestosterone, and estradiol, he raises the provocative hypotheses that there might be differential effects on cardiovascular and cerebrovascular risk related to endogenous testosterone and dihydrotestosterone concentrations.2 Based on the same epidemiological studies, Yeap postulates that there might be a U-shaped curve for circulating endogenous androgen concentrations such that lower and higher concentrations might confer greater risk of cardiovascular events and all-cause mortality than midrange concentrations. Shores demonstrates in a carefully done review of studies of large prescription databases (including >200 000 men) that testosterone therapy is not associated with overall mortality, myocardial infarction, stroke, or deep venous thrombosis events.3

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Would male hormonal contraceptives affect cardiovascular risk?

Cited by 7 publications

References 35 publications

The future of male contraception: a fertile ground

The future of male contraception: a fertile ground

Comparison of metabolic effects of the progestational androgens dimethandrolone undecanoate and 11β‐MNTDC in healthy men

Conclusions about testosterone therapy and cardiovascular risk

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