More evidence that taking extraneous DHT will surpress the HTPA and T production.
Perhaps sky-high rebounding DHT, after being surpressed by Finasteride, is what caused our T to drop after quitting?
Comparative Pharmacokinetics of Three Doses of Percutaneous Dihydrotestosterone Gel in Healthy Elderly Men–A Clinical Research Center Study
jcem.endojournals.org/cgi/content/full/83/8/2749
DISCUSSION:
In this study, we have shown that DHT, when administered daily as a gel at 0.7% DHT in hydroalcoholic solution, yields a dose-related increase in serum DHT levels in older men. The mean serum DHT levels rose gradually after gel application on the first day and were maintained at the same level through the duration of application.
The mean serum DHT levels achieved by the 16-mg (11.0 ± 1.7 nmol/L), and 32-mg (14.4 ± 1.5 nmol/L) doses on day 14 of the present DHT formulation were similar to those (14.7 ± 2.3 nmol/L) reported after administration of DHT (250 mg, applied as 125 mg twice daily) per day (14) using a 2.5% solution of DHT gel. The 2.5% DHT gel is the preparation available in Europe.
The mean serum DHT levels achieved by the 64-mg dose of DHT gel (26.1 ± 2.2 nmol/L) on day 14 were higher than that previously reported. Based on the known reported production rate of DHT and the mean serum DHT level (1), the percent bioavailable DHT from the DHT gel applied in the present study was estimated to be between 8–13%. This assumed that the clearance of the DHT was not altered with the application of exogenous DHT gel.
Possibly, lowering of the concentration of DHT in the current preparation and applying the gel over a large area of skin resulted in more efficient transfer of DHT into the circulation. Serum DHT levels then decreased gradually after stopping the application of the gel, reaching pretreatment levels 3–4 days later.
Concomitant with the rise in serum DHT levels after gel application, serum levels of T, free T, E2, FSH, and LH also showed consistent suppression. Previous studies demonstrated that DHT administration suppressed pulsatile LH secretion (13, 15), resulting in decreased production of T and E2.
Our study showed that significant suppression of serum T levels was present on day 14, and the suppression was most marked with the 64-mg dose. The degree of suppression of serum T with the 64-mg DHT dose was similar to previous reports by Schaison et al. (14), where 250 mg DHT gel was administered every day. Because of the short duration of DHT gel application (14 days), no significant change in SHBG levels was demonstrated in any of the treatment groups in our study.
Administration of the three doses of DHT gel led to dose-dependent increases in serum DHT AUC from 6- to 16-fold and suppression in T-AUC from 75–36% of baseline levels. The calculated total (molar) serum androgen levels, i.e. T + DHT levels, were elevated in all subjects but remained within the normal range of young adult men (13–50 nmol/L) and did not show a clear dose-response.
In hypogonadal men, where both basal endogenous serum DHT and T would be suppressed or low, administration of DHT would most likely result in a dose-related response in total androgen levels (primarily DHT), which was not evident in our study of mostly normal men. In future studies of the efficacy of DHT gel in hypogonadal men, our goal will be to study effectiveness when the serum DHT + T level is targeted at the low, medium, or high normal adult range.
Daily application of DHT gel to the skin caused no skin irritation in any of the subjects during the 14 days. There were no reports of rash, itchiness, weals, or redness. Similarly, there were no adverse clinical or biochemical events. Though serum hematocrit and red cell counts were slightly reduced at the end of the study, this could be accounted for by the volume of blood withdrawn during the study period. There were no clinically significant changes in clinical chemistry.
The possible advantages and disadvantages of DHT, over T, as androgen replacement include the absence of gynecomastia, because DHT is not aromatizable to E2. A previous uncontrolled study (17) showed that DHT administration to older men resulted in a 15% decrease in prostate volume despite high circulating DHT levels.
It has been demonstrated in human prostate cells in vitro and in animal studies in vivo that E2 acts synergistically with androgens to stimulate prostatic cell growth and prostatic hyperplasia (18, 19, 20, 21, 22, 23, 24, 25). Reduced E2 levels, which accompany percutaneous DHT administration, may result in decreased growth of the prostate despite high circulating DHT levels. Moreover, the effects of high serum DHT levels on the intraprostatic hormonal milieu are not known. Prostatic levels of DHT, T, and E2 have not been determined during DHT administration. It is also not known whether prostatic 5-reductase activity will increase or decrease when circulating DHT levels are elevated.
The effect of DHT, a nonaromatizable androgen, on lipids was previously studied (16). These researchers showed that long-term transdermal DHT in elderly men resulted in moderate decreases in plasma LDL and HDL cholesterol levels. However, Schaison et al. (14) reported that plasma LDL- and HDL-2 cholesterol, as well as apolipoprotein A and B, were not changed after 3 months of DHT treatment in hypogonadal men.
Clinical studies of men with mutations of the estrogen receptor (26) and aromatase enzyme (27) showed that these subjects were markedly osteopenic. The implications of these observations are that androgens exert their effect on bone via conversion to estrogens. Because DHT is not aromatizable, the question is raised whether DHT will have similar positive effects on bone mass and bone mineral density as an aromatizable androgen.
A number of considerations may influence the answer to the question and its implication for DHT treatment. Androgen receptors have been demonstrated in human bone cells (28, 29, 30, 31). The models for estrogen deficiency and decreased bone mineral density are based on humans and animals that had congenital, severe decrease in serum estrogens.
It is unknown whether acquired deficiency of estrogen, in the presence of normal androgens, will affect bone mass. Because DHT suppression of T and E2 is partial, the residual estrogen levels may be above the threshold for positive effects on bone. Because hypogonadal and older men are not estrogen-deficient from birth, DHT may still have positive actions on maintaining bone mass. These questions will be addressed in longer term efficacy studies of DHT gel administration in androgen deficient men. In addition, T and DHT may exert differential effects on the GH-insulin-like growth factor-I axis, which might affect body composition to different extents (32).
In summary, in this study, administration of graded doses of DHT gel resulted in dose-related increases in DHT levels, which could help to target the therapeutic total androgen levels to the low, medium, or high male range. Studies are in progress to assess the efficacy of DHT as a method of androgen therapy and determine whether its benefit-to-risk ratio is similar, better, or worse than T replacement for various specific endpoints.
The long-term effect of DHT on the prostate and lipid profile should be studied in comparison with T administration. Moreover, for DHT to find clinical utility, as androgen replacement therapy in older men, the long-term beneficial effects of DHT administration on bone, muscle and fat mass, sex function, mood, and sense of well-being have to be demonstrated.
