Potential of testosterone buciclate for male contraception: endocrine differences between responders and nonresponders.

Behre, Hermann M.; Baus, S; Kliesch, Sabine; Keck, Christoph; Simoni, Manuela; Nieschlag, Eberhard

doi:10.1210/jcem.80.8.7543113

Cited by 44 publications

(37 citation statements)

References 33 publications

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“…The longacting testosterone ester testosterone buciclate was identified under the auspices of WHO and NIH and showed a half-life of 29.5 days when tested in hypogonadal men, much longer than the 4.5 days of testosterone enanthate 9 . Suppression of spermatogenesis was comparable to that of weekly testosterone enanthate injections, reaching azoospermia in three out of eight volunteers after a single injection of 1200 mg of testosterone buciclate.…”

Section: T E S T O S T E R O N E a L O N Ementioning

confidence: 99%

Male contraception: A realistic option?

Nieschlag

2006

The European Journal of Contraception & Reproductive Health

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This review illustrates the principle of hormonal male contraception and gives an overview of current trials aiming at the development of a marketable hormonal contraceptive for men. The principle of male hormonal contraception is based on strong suppression of gonadotropins in order to arrest spermatogenesis at the spermatogonial stem cell level, thus leading to azoospermia or severe oligozoospermia. Until now, it has not been possible to interrupt spermatogenesis effectively without simultaneously inhibiting the production of androgens by Leydig cells, resulting in a deficiency of extra-testicular androgens. Therefore, testosterone needs to be replaced. By administering exogenous testosterone alone azoospermia can be reached in East Asians, whereas azoospermia is only achieved in two-thirds of Caucasian volunteers so that in these men an additional agent is required. Currently injectable testosterone combined with gestagens or administered as implants are being tested for possible licensing. Although scrotal and non-scrotal testosterone patches, orally administered testosterone undecanoate and testosterone gels are generally well tolerated and provide stable testosterone levels in the normal range, their use showed generally disappointing efficacy due to insufficient gonadotropin suppression. Further large multi-centre studies are required to establish the contraceptive efficacy of the most promising steroid combinations.

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Section: T E S T O S T E R O N E a L O N Ementioning

confidence: 99%

Male contraception: A realistic option?

Nieschlag

2006

The European Journal of Contraception & Reproductive Health

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“…Further clinical studies showed a maximum concentration 9 weeks postinjection of 13.1 T 1.8 nmol/L, the half-life being about 30 days. An injection of 1000 mg testosterone buciclate maintained testosterone serum levels within the normal range up to week 16 (95).…”

Section: Parenteral Deliverymentioning

confidence: 85%

Testosterone Hormone Replacement Therapy: State-of-the-Art and Emerging Technologies

et al. 2006

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In the human male, testosterone is the major circulating androgen. The clinical effects of androgen are numerous, and testosterone deficiency is associated with a number of clinical abnormalities. At present, a variety of preparations containing testosterone is available for the treatment of androgen deficiency. Ideally, those treatments have to produce and maintain physiologic serum concentrations of the hormone. This article reviews the current existing testosterone dosage forms on the market with their advantages and drawbacks and examines new and emerging technology developments concerning this therapy. In particular, the latest innovations in transdermal delivery are explored.

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“…The control of fertility is a major public health issue [1,2]. FSH receptor (FSHR) antagonists could potentially represent a novel nonsteroidal approach for contraception due to their specific action on ovarian tissue without affecting peripheral and central tissues.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Follicle-Stimulating Hormone-Induced Preovulatory Follicles in Rats Treated with a Nonsteroidal Negative Allosteric Modulator of Follicle-Stimulating Hormone Receptor1

Dias

Campo²,

Weaver

et al. 2014

Biology of Reproduction

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We previously described a negative allosteric modulator (NAM) of FSHR (ADX61623) that blocked FSH-induced cAMP and progesterone production but did not block estradiol production. That FSHR NAM did not affect FSH-induced preovulatory follicle development as evidenced by the lack of an effect on the number of FSH-dependent oocytes found in the ampullae following ovulation with hCG. A goal is the development of a nonsteroidal contraceptive. Toward this end, a high-throughput screen using human FSHR identified an additional nonsteroidal small molecule (ADX68692). Although ADX68692 behaved like ADX61623 in inhibiting production of cAMP and progesterone, it also inhibited FSH-induced estradiol in an in vitro rat granulosa primary cell culture bioassay. When immature, noncycling female rats were injected subcutaneously or by oral dosing prior to exogenous FSH administration, it was found that ADX68692 decreased the number of oocytes recovered from the ampullae. The estrous cycles of mature female rats were disrupted by administration by oral gavage of 25 mg/kg and 10 mg/kg ADX68692. In the highest dose tested (25 mg/kg), 55% of animals cohabited with mature males had implantation sites compared to 33% in the 10 mg/kg group and 77% in the control group. A surprising finding was that a structural analog ADX68693, while effectively blocking progesterone production with similar efficacy as ADX68692, did not block estrogen production and despite better oral availability did not decrease the number of oocytes found in the ampullae even when used at 100 mg/kg. These data demonstrate that because of biased antagonism of the FSHR, nonsteroidal contraception requires that both arms of the FSHR steroidogenic pathway must be effectively blocked, particularly estrogen biosynthesis. Thus, a corollary to these findings is that it seems reasonable to propose that the estrogen-dependent diseases such as endometriosis may benefit from inhibition of FSH action at the ovary using the FSHR NAM approach.

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Potential of testosterone buciclate for male contraception: endocrine differences between responders and nonresponders.

Cited by 44 publications

References 33 publications

Male contraception: A realistic option?

Male contraception: A realistic option?

Testosterone Hormone Replacement Therapy: State-of-the-Art and Emerging Technologies

Inhibition of Follicle-Stimulating Hormone-Induced Preovulatory Follicles in Rats Treated with a Nonsteroidal Negative Allosteric Modulator of Follicle-Stimulating Hormone Receptor1

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