Comparison of 7α-methyl-19-nortestosterone effectiveness alone or combined with progestins on androgen receptor mediated-transactivation

Abstract

7a-methyl-19-nortestosterone (MENT) is an androgen with potent gonadotropin inhibitory activity and prostate-sparing effects. These attributes give MENT advantages over testosterone as a male contraceptive, but, as in the case of testosterone, a partial dose-dependent suppression of spermatogenesis has been observed. Combination of testosterone or MENT with synthetic progestins improves the rate of azoospermia; however, it is unknown whether these combinations affect hormone androgenicity or exert synergistic effects via progestational or androgenic interaction. Herein, using transactivation assays, we examined the ability of MENT alone or combined with several 19-nor-derived synthetic progestins to activate androgen receptor (AR)-dependent gene transcription. In addition, the capability of 7a-methyl-estradiol (7a-methyl-E 2 ), an aromatized metabolite of MENT, to transactivate gene transcription via estrogen receptor a (ERa; ESR1) or ERb (ESR2) was also investigated. As expected, MENT induced gene transactivation through either the progesterone receptor (PGR) or the AR. MENT was as efficient as progesterone in activating PGR-mediated reporter gene expression, but it was ten times more potent than testosterone and dihydrotestoterone in activating of AR-driven gene expression. The addition of increasing concentrations of other 19-nortestosterone derivatives (norethisterone or levonorgestrel) did not affect, in a significant manner, the ability of MENT to activate AR-dependent reporter gene transcription. The same results were obtained with different cell lines. 7a-Methyl-E 2 resulted in potent estrogen activity via both ER subtypes with efficiency similar to natural E 2 . These results suggest that the addition of 19-nortestosterone-derived progestins, as a hormonal adjuvant in male fertility strategies for effective spermatogenic suppression, does not display any detrimental effect that would interfere with MENT androgenic transcriptional activity.

Emerging concepts in male contraception: a narrative review of novel, hormonal and non-hormonal options

“…66 7α-Methyl-19-nortestosterone 7α-Methyl-19-nortestosterone (MENT) is a synthetic androgen with activity at both androgen and progesterone receptors. 67 It is more potent than testosterone and has more resistance to 5-α-reductase. 68 MENT acetate was developed as a long-term birth control using ethylene vinyl acetate implants.…”

A review of designer anabolic steroids in equine sports

“…Dietary supplements labelled to contain trestolone such as TR3ST (Olympus Labs) and 7‐MENT Alpha (Wyked Labs) have become available in recent years. It has been shown in bioassays with HeLa cells transfected with the human androgen receptor, human AR CALUX bioassays, and in vivo rat models to be a potent androgen, as well as exhibit strong binding to the human progesterone receptor . Trestolone has also been recently explored for use as a human male contraceptive as it has been shown to inhibit spermatogenesis without inducing androgen deficiency .…”

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“…MENT is synthetic androgen with potent gonadotropin inhibitory activity and prostate sparing effects. 8 This synthetic androgen is more potent than testosterone, it is resistant to 5 α-reduction, and has diffusion characteristics that make it easy to be administered in the form of depot implant. However, it has a similar side effect profile with testosterone and only provides partial dose-dependent suppression of spermatogenesis.…”