The science and data disagrees with all your theories. Keep ignoring the data. MENT not being able to 5AR has ZERO effect on the drugs ability to maintain sexual function. "An inadequate testosterone level causes undesirable effects such as
fatigue, loss of
skeletal muscle mass, reduced
libido, and weight gain. However, the androgenic and anabolic properties of trestolone largely ameliorate this problem essentially, trestolone replaces testosterone's role as the primary male hormone in the body."
I read the two papers to which this copy and pasted passage from the Wikipedia entry for Trestolone refer:
[1] Nieschlag, E., Kumar, N., & Sitruk-Ware, R. (2013). 7α-Methyl-19-nortestosterone (MENTR): the Population Council’s contribution to research on male contraception and treatment of hypogonadism. Contraception, 87(3), 288–295. doi:10.1016/j.contraception.2012.08.036
[2] Sundaram, K., Kumar, N., & Bardin, C. W. (1993). 7α-Methyl-Nortestosterone (MENT): The Optimal Androgen for Male Contraception. Annals of Medicine, 25(2), 199–205. doi:10.3109/07853899309164168
And I must say that these offered nothing new of note, and were an waste of time having read them.
From [1], the only study where a dose > that used by your prior reference (actually, provided by
@Cridi887) to Anderson, R. A., Martin, C. W., et al. used 3X 171 mg MENT Ace implants. The results were abysmal, and attributed to implant failure (but do not support enhanced sexual function at bodybuilding doses). The aforementioned purportedly adequate dose, here, failed to support androgenicity and suppress spermatogenesis. Indeed, Walton, et al. as cited herein (and mentioned previously) showed that "2 of 13 (15%) MENT subjects withdrew after 8 weeks of treatment due to low libido & erectile dysfunction...Adverse events included reduced libido & erectile function in 4 additional subjects in the MENT group who completed treatment (6/13, or 46%) [these adverse effects were not reported by any subject in the testosterone group]...Due to the incidence of reports of low libido and early withdrawal in the MENT group, it was decided in consultation with the study Data Monitoring and Safety Committe to shorten the MENT treatment period to 24 weeks whereas men in the testosterone group completed 48 weeks of treatment."
I think it's fair to characterize Anderson, et al. as an outlier; not to mind the fact that no study has looked at up to 600 mg/wk testosterone enanthate equivalent dose/response so as to dismiss the observation (not yet subjected to rigorous study) that bodybuilding doses of solo MENT do not apparently support sexual function.
The study by Sundaram, et al. [2], discusses the - and I accept this as the majority - view that 5α-reduction/amplification per se is unnecessary to support sexual function, but rather merely contributed to BPH/prostate growth in adults (it supports sexual dimorphism during gestation/maturation). I already know that this is the majority view, and it has until fairly recently been shared by myself.
The experiences of MENT users is actually one bit of evidence that made me rethink it. So too is the general lackluster experience in men (I believe women are far more sensitive to androgenic effects in enhancing sexual potency, libido, etc.) of any nontestosterone base, and noteworthy enhancement by Halo.
I believe that, just as the
process of aromatization has been shown to be more complex than commonly understood; the same is true for 5α-reduction. I will present evidence that the process per se (
in situ aromatization) exerts distinct effects, e.g., on circulating IGF-I; and that this belies a rudimentary view, still clung to, that AAS drug design benefits from reducing the purportedly deleterious effects of T mediated by aromatization to E2 & 5α-reduction to DHT.
To illustrate the complexity of aromatization and its value as a discrete (here, myogenic & mitogenic) process
E2 (the aromatic product of T) reduces IGF-I. This is clear from exogenous estrogen administration (e.g., ethinyl estradiol reduces IGF-I to the tune of 30%).
Women that are
not on exogenous estrogens have higher IGF-I values than their age-matched male counterparts (until menopausal age, E2 decline).
The reason that both of these can be true, is that E2 unleashes GH secretion (feedback withdrawal) by increasing IGFBP-1 (reducing IGF-I bioavailability). As a result, women have
much higher GH concentrations than age-matched men, and just slightly higher IGF-I concentrations.
Women are far less responsive to rhGH, and require
higher doses than men of similar size (but experience worse side effects). For women that are on exogenous estrogens, this is even more pronounced. For example, a daily dose of 0.6 IU was sufficient as replacement in men whereas 1.2 IU (or 1.8 IU) was required in the women. Clinical guidelines for rhGH replacement provide that rhGH dose be reduced by 50% if a woman is switched from oral estrogen to transdermal estrogen and then to reduced by one third if the woman discontinues transdermal estrogen.
In men, E2 is the product of T =(Aromatase)=> E2; all of it.
T (and aromatizing androgen generally) augment E2, and yet, clearly increase IGF-I values potently.
This is because it is the process of
in situ aromatization per se that enhances IGF-I levels in men. Tamoxifen reduces IGF-I. So does exogenous estrogen.
Exogenous T:
- significantly and consistently increases plasma total IGF-I concentrations
- elevates underlying basal (non-pulsatile) GH release
- does not increase IGFBP-1 concentrations (therefore, unlike exogenous estradiol, there is no compensatory mechanism to mitigate IGF-I increases despite heightened GHRH and GHRP actions).
It is my hypothesis (a construct at this point) that aromatization (process) augments IGF-I independently and asynchronously from its substrate (T) & product (E2).
There are discrete signaling pathways leading to high local IGF-I concentration.
This data, then, contravenes the (in my view) outmoded view of aromatase as a deleterious function of T, to be abolished by drug design of nonaromatizable androgen.
5α-reduction as a discrete process
To distinguish from the understanding of aromatization as a discrete (mitogenic & myogenic) process, admittedly my data on the nature of 5α-reduction as an indispensible (sexual function) process is not as robust. Importantly, *I* am entirely willing to alter my hypothesis (not yet a more fleshed out construct) on this if I see data that dismisses these arguments & supporting logic:
Dutasteride is an inhibitor of both 5α-reductase type 1 & 2. Type 1, notably, is expressed in brain (and liver, kidney, skin). Dutasteride is associated with sexual dysfunction.
Finasteride is supposedly a selective inhibitor of 5 type 1, yet the post-finasteride syndrome is associated with persistent symptoms of sexual impotency and dysfunction; lower cerebrospinal fluid levels of allopregnanolone, isopregnanolone, and DHT, and higher levels of testosterone and estradiol have been observed in subjects that suffer from the post-finasteride syndrome.
5α-reductase, then, appears to be an important discrete pathway involved in sexual function, aside from merely modulating growth of prostate tissue.
This is the basis for my belief that 5α-reductase per se confers sexual potency benefits beyond merely amplification of T to DHT.
I believe that there is a teleological basis for the importance of these pathways - T, as the primary male androgen, is a good substrate for both enzymes (aromatase & 5α-reductase) and eons of evolutionary pressures have reinforced various characteristically male traits (e.g., increased physicality & body size; increased sexual potency) via these processes.
