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PubMed1985

Dose- and time-dependent effects of a dimeric ethynodiol-testosterone depot-preparation in female rat.

The time- and dose-dependent effects of a dimeric ethynodiol-testosterone ester upon intact and hemi-castrated female rats were compared to those of equivalent doses of norethisterone enanthate plus testosterone enanthate. In intact rats, serum LH was markedly suppressed for at least 8 weeks after a single i.m. injection of 10 or 20 mg of the dimer which exceeded the depot-effect of the combination of the enanthates. A biphasic time-and dose-dependent effect of the dimeric ester upon ovarian and uterine weight was observed. During first 2 weeks following the injection there was a pronounced enlargement of corpora lutea and a marked enhancement of progesterone secretion, probably due to a direct stimulation by the androgens. At the same time, the uteri were markedly enlarged. During the following weeks, the ovaries became progressively smaller and showed degenerative changes, the steroid levels decreased and the uteri became atrophic. When hemi-castrated rats were injected once with 1 and 5 mg of the dimer, LH became suppressed, and the compensatory hypertrophy of the ovary was inhibited. At higher doses, the weight of the ovary and uterus was increased, and the luteal function was stimulated. The results indicate that, even though the gonadotropins are suppressed, there is possibly a direct stimulatory effect of high doses of the intact dimeric molecule upon the uterus, while the stimulation of the corpus luteum function is due to an interference of the transiently elevated testosterone level with ovarian steroid biosynthesis.

Animals↗
PubMed1978

Progestational potency of oral contraceptives: a polemic.

Dickey and Stone have attempted an evaluation of progestational potencies of oral contraceptives based upon such uterine criteria as subnuclear vacuolization and delay of menses. Their review, unfortunately, is marred by numerous errors which vitiate the potency estimates. The actions of progestagens in target organs depend upon the specific binding of the compounds to a protein receptor that is produced by estrogen treatment. Potency of hormones depends ultimately upon this binding. Since it seems unlikely that specific binding occurs in such nontarget sites as the blood vessels, direct potency relationships are highly improbable between diverse phenomena. Possible relationships between oral contraceptives and specific side effects must be studied in relationship to individual side effects and particular contraceptive products. Possible coincidental activities, no matter how analyzed, are unlikely to contribute meaningfully to our understanding of these drugs.

Castration↗