Dr Scally, why do you think it is a poor study on ITT?
In my opinion, the study, “Coviello AD et al., (2005), Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression, J Clin Endocrinol Metab. 2005 May;90(5):2595-602,” has a poor trial design and amounts to little new science.
The purpose of the study is related to spermatogenesis. The abstract begins,
”In previous studies of testicular biopsy tissue from healthy men, intratesticular testosterone (ITT) has been shown to be much higher than serum testosterone (T), suggesting that high ITT is needed relative to serum T for normal spermatogenesis in men. However, the quantitative relationship between ITT and spermatogenesis is not known. To begin to address this issue experimentally, we determined the dose-response relationship between human chorionic gonadotropin (hCG) and ITT to ascertain the minimum dose needed to maintain ITT in the normal range.”
The authors point out the most glaring problem with the study in these sentences. First, the study deals with spermatogenesis, but the study fails to include any results for spermatogenesis. It is impossible to relate any of their findings to spermatogenesis. They even discuss that spermatogenesis occurs in the face of altered, including low, ITT.
Second, the study apparently hopes to extend our understanding of male contraception, thus the use of TE 200 mg/week. This is a common dose schedule in male contraceptive studies. The important and salient fact of male contraceptive studies is that despite high serum T levels (and corresponding low ITT) and low gonadotropin (FSH & LH) levels spermatogenesis still occurs.
The study continues,
“Experimental suppression of LH and FSH levels profoundly decreases testosterone production and dramatically reduces spermatogenesis in men.” The study did not include spermatogenesis and therefore impossible to draw any correlation with ITT, but also FSH and LH, the gonadotropins. In what is another blunder, the study used hCG. hCG is not a factor in male contraception! hCG possesses LH and FSH stimulating abilities. It will provide no information for male contraception, none.
For a proper trial design see: “Page ST, Kalhorn TF, Bremner WJ, Anawalt BD, Matsumoto AM, Amory JK. Intratesticular Androgens and Spermatogenesis During Severe Gonadotropin Suppression Induced by Male Hormonal Contraceptive Treatment. J Androl 2007;28(5):734-41” and “Matthiesson KL, McLachlan RI, O'Donnell L, et al. The Relative Roles of Follicle-Stimulating Hormone and Luteinizing Hormone in Maintaining Spermatogonial Maturation and Spermiation in Normal Men. J Clin Endocrinol Metab 2006;91(10):3962-9.” Both studies include endpoints of spermatogenesis.
So what did the study provide? This is what I find most comical. They took
NORMAL males, including spermatogenesis and exposed them to TE to suppress LH, FSH, and ITT. Can anyone guess what will happen when administered hCG? Duh… The ITT increased. This is totally expected and provides nothing more to move forward the development of a male contraceptive. My own suspicion is that this study is part of a larger study that includes spermatogenesis endpoints. There is still the larger problem that hCG does not correlate to FSH and LH.
Many posters have linked to the article as support for their mode of hCG administration in TRT. As I have said on multiple posts, this study deals with intratesticular testosterone (ITT) and nothing to say about serum T production or otherwise.
The study does include a bar graph of serum T levels with hCG dosing. hCG was delivered SC
EVERY OTHER DAY (EOD) for 3 wk: 0 (saline placebo), 125, 250, or 500 IU hCG. The placebo group served as the control group. The lowest hCG dose (125) group had serum T levels similar to those in the placebo group, whereas higher serum levels were achieved in the two highest hCG groups, 250 and 500 IU. The administration of hCG is EOD. If you are administering hCG less frequently it is expected the effect would be less.
In “Matthiesson KL, McLachlan RI, O'Donnell L, et al. The Relative Roles of Follicle-Stimulating Hormone and Luteinizing Hormone in Maintaining Spermatogonial Maturation and Spermiation in Normal Men. J Clin Endocrinol Metab 2006;91(10):3962-9,” hCG was also included.
Changes in serum T (A) levels in 18 men (n = 6/group) randomized to receive:
1) T implant, 800 mg sc, + DMPA, 150 mg im once;
2) T implant+DMPA+FSH, 300 IU sc twice weekly; or
3) T implant+DMPA+hCG, 1000 IU sc twice weekly.
Serum levels are shown at screening and then weekly thereafter. Data are shown as mean ? SEM, n = 6/group. Shaded areas represent normal reference intervals. No differences in T levels from baseline were determined in the T+DMPA group.
Higher levels from baseline were found in the T+DMPA+FSH group, d 14–28 and 42 (P < 0.05), and the T+DMPA+hCG group, d 7–42 except on d 35 (P < 0.05).
