Determinants of the Rate and Extent of Spermatogenic Suppression during Hormonal Male Contraception: An Integrated Analysis

Abstract

Male hormonal contraceptives can be practically applied to a wide range of men but require coadministration of an androgen with a second agent (i.e. progestin) for earlier and more complete suppression of sperm output. Whereas considerable progress has been made toward defining clinically effective combinations, further optimization of androgen-progestin treatment regimens is still required.

Does ethnicity matter in male hormonal contraceptive efficacy?

“…In this analysis, we showed that the independent factors which most strongly influence the odds of eventual suppression are ethnicity and the use of a progestin as part of the treatment regimen (Table 1). 27 This is illustrated by actual suppression Ethnicity and male contraception N Ilani et al 580 rates observed in 1756 men treated with various male hormonal contraceptive regimens (Figure 1, using data from Ref. 27), which clearly shows that: (i) only up to 80% of Caucasian men suppress sperm output to ,10 6 ml 21 when received treatments that contain only androgens; (ii) up to 90% of East Asian men will adequately suppress sperm output when treated only with androgens; ( iii) the addition of a progestin increases to over 90% the proportion of Caucasian men who eventually suppress sperm output to ,10 6 ml 21 .…”

“…27 This is illustrated by actual suppression Ethnicity and male contraception N Ilani et al 580 rates observed in 1756 men treated with various male hormonal contraceptive regimens (Figure 1, using data from Ref. 27), which clearly shows that: (i) only up to 80% of Caucasian men suppress sperm output to ,10 6 ml 21 when received treatments that contain only androgens; (ii) up to 90% of East Asian men will adequately suppress sperm output when treated only with androgens; ( iii) the addition of a progestin increases to over 90% the proportion of Caucasian men who eventually suppress sperm output to ,10 6 ml 21 . This proportion exceeds that observed by East Asian men treated with androgens alone; and (iv) nearly all East Asian men treated with androgen-progestin male hormonal contraceptive will eventually suppress sperm output to ,10 6 ml 21 .…”

“…On the other hand, androgen-progestin male hormonal contraceptive combinations are highly promising since both the rate and extent of spermatogenic suppression are increased by up to twofold. 27 However, the scantiness of androgen-progestin hormonal exposure information with contraceptive efficacy as a primary endpoint is an important limitation for the field. Whether a specific progestin is superior to another progestin is also unknown, since available studies in humans have been underpowered to determine whether certain progestins more effectively suppress sperm output than others.…”

“…Whether a specific progestin is superior to another progestin is also unknown, since available studies in humans have been underpowered to determine whether certain progestins more effectively suppress sperm output than others. 27 However, this is likely to be the case because progestins differ in anti-ovulatory potency, ability to support pregnancy, and binding and specific activation of progesterone relative to other steroid receptors. 28 It is also not known whether the ratios of the androgen to progestin dose and levels achieved in the body are important factors for effectiveness and the development of adverse effects.…”

“…Figure 1 Suppression of sperm output during treatment with MHC, using data taken from Ref. 27. The Kaplan-Meier graph shows the actual proportion of East Asian (dark symbol) and Caucasian (white symbol) men who have suppressed sperm concentrations to one million sperm per ml.…”