Induction of Male Sexual Behavior in the Rat by 7α-Methyl-19-Nortestosterone, an Androgen that does not Undergo 5α-Reduction1

Moralí, Gabriela; Lemus, Ana E.; Munguía, R; Arteaga, Marcela; Pérez‐Palacios, Gregorio; Sundaram, K.; Kumar, Narender; Bardin, C. Wayne

doi:10.1095/biolreprod49.3.577

Cited by 32 publications

(13 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5␣-Reductase is also present in the human brain (37); however, the isoform present in cerebral cortical tissue is type I rather than type II, which predominates in reproductive tract tissues (38 -40). In castrate male rodents, MENT fully restores sexual behavior (45,46), but does not restore aggressive behavior, in contrast to testosterone, which restored both (13). In castrate male rodents, MENT fully restores sexual behavior (45,46), but does not restore aggressive behavior, in contrast to testosterone, which restored both (13).…”

Section: Effects On Moodmentioning

confidence: 91%

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

Anderson

Martin²,

Kung

et al. 1999

The Journal of Clinical Endocrinology &Amp; Metabolism

View full text Add to dashboard Cite

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...

show abstract

Section: Effects On Moodmentioning

confidence: 91%

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

Anderson

Martin²,

Kung

et al. 1999

The Journal of Clinical Endocrinology &Amp; Metabolism

View full text Add to dashboard Cite

show abstract

“…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].…”

Section: Emerging Strategies Of Hormone-related Therapies In Alzhmentioning

confidence: 99%

“…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]. The effects of MENT on neural function are virtually unknown, but it has been shown to mimic the ability of testosterone to induce sexual behavior in castrated rats [224] and is a robust regulator of the hypothalamic-pituitary-gonadal axis, suggesting neural efficacy.…”

Section: Emerging Strategies Of Hormone-related Therapies In Alzhmentioning

confidence: 99%

Protective actions of sex steroid hormones in Alzheimer’s disease

Pike

Carroll

Rosario

et al. 2009

Frontiers in Neuroendocrinology

440

356

View full text Add to dashboard Cite

Risk for Alzheimer’s disease (AD) is associated with age-related loss of sex steroid hormones in both women and men. In postmenopausal women, the precipitous depletion of estrogens and progestogens is hypothesized to increase susceptibility to AD pathogenesis, a concept largely supported by epidemiological evidence but refuted by some clinical findings. Experimental evidence suggests that estrogens have numerous neuroprotective actions relevant to prevention of AD, in particular promotion of neuron viability and reduction of β-amyloid accumulation, a critical factor in the initiation and progression of AD. Recent findings suggest neural responsiveness to estrogen can diminish with age, reducing neuroprotective actions of estrogen and, consequently, potentially limiting the utility of hormone therapies in aged women. In addition, estrogen neuroprotective actions are also modulated by progestogens. Specifically, continuous progestogen exposure is associated with inhibition of estrogen actions whereas cyclic delivery of progestogens may enhance neural benefits of estrogen. In recent years, emerging literature has begun to elucidate a parallel relationship of sex steroid hormones and AD risk in men. Normal age-related testosterone loss in men is associated with increased risk to several diseases including AD. Like estrogen, testosterone has been established as an endogenous neuroprotective factor that not only increases neuronal resilience against AD-related insults, but also reduces β- amyloid accumulation. Androgen neuroprotective effects are mediated both directly by activation of androgen pathways and indirectly by aromatization to estradiol and initiation of protective estrogen signaling mechanisms. The successful use of hormone therapies in aging men and women to delay, prevent, and or treat AD will require additional research to optimize key parameters of hormone therapy and may benefit from the continuing development of selective estrogen and androgen receptor modulators.

show abstract

“…SARMs that are not 5 -reductase substrates and thus do not form DHT or DHTlike derivatives have relatively low androgen action in prostate since prostate growth depends largely on the actions of DHT rather than testosterone [221][222][223][224][225][226][227]. There are several promising synthetic androgens with varied affinity for AR and androgenic activity, including 7 -methyl-19-nortestosterone, commonly called MENT [226][227][228]. MENT is promising because it shows low androgen activity in prostate but is more potent than testosterone in other peripheral androgen-responsive tissues including bone and muscle [226,227,229].…”

Section: Neuroactive Selective Androgen Recep-tor Modulatorsmentioning

confidence: 99%

The Potential Use of Hormone-Based Therapeutics for the Treatment of Alzheimers Disease

Carroll¹,

Rosario²

2012

CAR

View full text Add to dashboard Cite

In both men and women, age-related loss of sex steroid hormones has been linked to an increased risk for Alzheimer's disease (AD). The primary female hormone estrogen, and the primary male hormone testosterone have numerous protective effects in the brain relevant to the prevention of AD such as the promotion of neuron viability, reduction of β- amyloid accumulation and alleviation of tau hyperphosphorylation. Therefore it has been hypothesized that the precipitous loss of these hormones either through menopause or normal aging, can increase susceptibility to AD pathogenesis. This review will discuss the basic science research and epidemiological evidence largely supporting this hypothesis, as well as the estrogen-based hormone therapy clinical findings that have recently shed doubt on this theory. The complications associated with estrogen-based hormone therapy such as the inclusion of a progestogen, hormone responsiveness with age, and natural vs. synthetic hormones will be discussed. Further, we will outline the cancer risks facing both estrogen and testosterone-based hormone therapy. Most importantly, this review will discuss the present and future strategies to translate the neuroprotective properties of sex steroid hormones into safe and efficacious treatments for AD. One of the most promising translational tools thus far may be the development of selective estrogen and androgen receptor modulators. However, additional research is needed to optimize these and other translational tools towards the successful use of hormone therapies in both men and women to delay, prevent, and or treat AD.

show abstract

Induction of Male Sexual Behavior in the Rat by 7α-Methyl-19-Nortestosterone, an Androgen that does not Undergo 5α-Reduction1

Cited by 32 publications

References 27 publications

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

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

Protective actions of sex steroid hormones in Alzheimer’s disease

The Potential Use of Hormone-Based Therapeutics for the Treatment of Alzheimers Disease

Contact Info

Product

Resources

About