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Long-acting hormonal contraceptives for women.

Following the development and widespread use of oral hormonal contraceptives, it became evident that alternative long-acting delivery systems would be required to improve contraceptive practice in some cultural settings where injectable or subdermal routes of administration are preferred. Nowadays, long-acting contraceptives constitute an important option in family planning services in many parts of the world. Indeed, two long-acting injectable contraceptives containing just a synthetic progestogen (depot-medroxyprogesterone acetate (DMPA) and norethisterone enantate (NET-EN)) have been in clinical practice for more than 20 years. The World Health Organization's (WHO) Special Programme of Research in Human Reproduction, in collaboration with the U.S. National Institute of Child Health and Human Development (NICHD) and universities primarily in developing countries undertook a synthesis programme aimed at producing an improved injectable preparation by developing new derivatives of known steroids. One such compound (levonorgestrel 17-butanoate) is now at the stage of Phase II clinical testing. In addition, the Special Programme has developed and improved once-a-month injectable formulations and assessed their safety and efficacy in different countries worldwide. After large scale clinical testing, at least two progestogen-estrogen combinations have reached the point of introductory trials.

Aniline Compounds↗

Immature rat uterotrophic assay of 18 chemicals and Hershberger assay of 30 chemicals.

We performed an immature rat uterotrophic assay of 18 chemicals and Hershberger assay of 30 chemicals to assess the relationship between the results of two assays. The chemicals tested by the uterotopic assay were 4-n-amylphenol, p-dodecyl-phenol, p-(tert-pentyl)phenol, 4-cyclohexylphenol, 4-(1-adamantyl)phenol, 4,4'-thiobis-phenol, diphenyl-p-phenylenediamine, 4-hydroxyazobenzene, 4-(phenylmethyl)phenol, 4,4'-(hexafluoroisopropylidene)diphenol, 2,2-bis(4-hydroxyphenyl)-4-methyl-n-pentane, 4,4'-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol, 4,4'-dihydroxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 4-hydroxybenzophenone, 2,4,4'-trihydroxybenzophenone, testosterone enanthate, and methyltestosterone. The chemicals tested by the Hershberger assay were the 18 chemicals tested in the uterotrophic assay plus the following: 17 alpha estradiol, estrone, equilin, norethindrone, norgestrel, ethynyl estradiol, bisphenol A, bisphenol B, bisphenol F, 4-tert-octylphenol, p-cumyl phenol, and nonylphenol. All chemicals examined in this study were positive in a reporter gene assay for ER-alpha. In the immature rat uterotrophic assay, all chemicals induced uterotrophy and p-(tert-pentyl)phenol, 4,4'-thiobis-phenol, 4-(phenylmethyl)phenol, 4,4'-(hexafluoroisopropylidene)diphenol, 2,2-bis(4-hydroxyphenyl)-4-methyl-n-pentane, 4,4'-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol, 4,4'-dihydroxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 4-hydroxybenzophenone, and 2,4,4'-trihydroxybenzophenone exerted both estrogen agonistic effect and reduced the estrogenic effect of ethynylestradiol. In the Hershberger assay, a clear androgen agonistic effect was detected in the androgen derivatives testosterone enanthate and methyltestosterone.

Androgen Antagonists↗

Potential of norethisterone enanthate for male contraception: pharmacokinetics and suppression of pituitary and gonadal function.

OBJECTIVE: Gestagens are known to suppress gonadotrophins in women and are currently also under investigation for the development of hormonal male contraceptives. The aim of the study was to assess the potential of norethisterone enanthate (NETE) for male contraception. DESIGN AND MEASUREMENTS: The suppressive effect of a single injection of 200 mg NETE on serum gonadotrophins, serum testosterone, lipids, spermatogenesis, well-being and sexual function was evaluated in seven healthy men. RESULTS: In this single dose study treatment was well tolerated by all volunteers. NETE led to a rapid, profound and significant suppression of serum LH (day 6 - day 10), FSH (day 2 - day 29), testosterone (day 1 - day 29 and day 35) and SHBG (day 6 - day 35). At study end sperm counts were significantly suppressed. Numbers of spontaneous erections (day 17, 23 and 26), number of sexual fantasies (day 20 and 23) as well as libido (day 20 and 26) were significantly decreased compared to baseline. All other parameters including lipids, augmented glucose, testicular volume and well-being showed no significant alterations. CONCLUSION: Because of its strong, rapid and sustained suppression of serum FSH and testosterone norethisterone enanthate offers great potential for hormonal male contraception if combined with testosterone esters.

Adult↗