7α-Methyl-19-Nortestosterone Maintains Sexual Behavior and Mood in Hypogonadal Men*

Abstract

The synthetic steroid 7alpha-methyl-19-nortestosterone (MENT) is a potent androgen that is resistant to 5alpha-reductase. It thus has decreased activity at the prostate and may have advantages over testosterone-based regimens in long term treatment or as part of a male contraceptive. Administration to eugonadal men results in suppression of gonadotropins, but its ability to support androgen-dependent behavior has not been investigated. For sustained release administration, MENT acetate was used, because its diffusion characteristics were more suitable for use in implants. However, upon release the acetate is rapidly hydrolyzed, and MENT is the biologically active moiety in circulation. We studied the effects of MENT on sexual interest and activity, spontaneous erection, and mood states in comparison with testosterone enanthate (TE) in 20 Caucasian and Chinese hypogonadal men recruited in Edinburgh and Hong Kong (n = 10 in each center). Outcomes were measured using a combination of daily diaries, semistructured interviews, and questionnaires. Nocturnal penile tumescence (NPT) was also recorded in the Edinburgh group. After withdrawal of androgen replacement treatment (wash-out phase) for a minimum of 6 weeks, subjects were randomized to two groups in a cross-over design. Drug treatment regimens were of 6-week duration and consisted of two implants, each containing 115 mg MENT acetate, inserted s.c. into the upper arm and removed after 6 weeks and two injections of TE (200 mg, i.m.) 3 weeks apart. MENT treatment resulted in stable plasma MENT concentrations of 1.4 +/- 0.1 nmol/L after 3 weeks and 1.3 +/- 0.1 nmol/L after 6 weeks (mean +/- SEM; all men). Nadir testosterone concentrations were 3.6 +/- 0.6 nmol/L at the end of the wash-out phase and 9.4 +/- 0.6 nmol/L 3 weeks after each injection. There were no differences in hormone concentrations between centers. There were no adverse toxicological effects. There were only minor differences between the two treatments. Both MENT and TE treatment resulted in significant increases in sexual interest and activity, spontaneous erection (both by self-report and NPT measurement), and increases in positive moods, with decreases in negative moods in the Edinburgh group. In the Hong Kong group, both treatments increased waking erection, with a trend toward increased sexual interest and activity. Mood states appeared to be less affected during the wash-out phase than in Edinburgh men and showed no significant response to either treatment. These results demonstrate that MENT has similar effects on sexual activity and mood states as testosterone in hypogonadal men. As NPT is a physiological androgen-dependant outcome, these data provide further evidence for the androgenicity of MENT. The lack of detected effect of either androgen in Hong Kong men other than on waking erection illustrates the importance of the cultural context of symptomatology and its measurement. The appropriate dose of MENT remains to be determined, but these results support its development as a potential andr...

A Simple Self‐Report Diary for Assessing Psychosexual Function in Hypogonadal Men

“…However, during testosterone replacement therapy in hypogonadal men, the positive mood scale improved significantly in both groups and the negative mood scale improved in the second comparison group. This change in mood had been previously reported by Burris et al (1992), Anderson et al (1999), O'Connor et al (2002) using other questionnaires as well as Wang et al (1996b, 2000) using this diary. We note that these changes in mood were not correlated with change in testosterone levels from baseline or value of testosterone levels after 30 days of treatment.…”

“…The exact relationship between androgens and mood is less clear. Studies have shown that testosterone replacement therapy improves the general well‐being and the mood states of hypogonadal men (O'Carroll et al, 1985; Wang et al, 1996b; Anderson et al, 1999; Wang et al, 2000; O'Conner et al, 2002). Others failed to demonstrate this positive effect of testosterone on mood (Davidson et al, 1979).…”

Protective actions of sex steroid hormones in Alzheimer’s disease

“…SARMs that are not 5α-reductase substrates or form DHT-like derivatives with weak androgenic activity have low androgen action in prostate [109, 189, 201, 212, 245, 301, 342]. A promising SARM in this category is 7α-methyl-19-nortestosterone, commonly called MENT [224, 301, 342], which was developed by the Population Council and is currently in clinical trials as an androgen therapy for hypogonadal men [11, 345]. MENT shows low androgen activity in prostate but is more potent than T in other peripheral androgen-responsive tissues including bone [77, 301, 342] and muscle [77, 301, 342].…”

Testosterone and Sleep-Related Erections: An Overview*

“…On the other hand, Anderson et al. [142] found that the administration of 7α‐methyl‐19‐nortestosterone (MENT) also improves NPT in hypogonadal men from Edinburgh. However, MENT cannot be metabolized through the 5α‐pathway to 5α‐metabolites.…”