Harry W. Rudel

Low Doses of Progestogen as an Approach to Fertility Control

A clinical program was undertaken to establish the contraceptive effectiveness of minimal hormonal supplementation with chloramadinone acetate .5 mg given daily in both a cyclic and continuous pattern. Nonlactating women of proven fertility 36 years and under were given the drug daily as a contraceptive. They were all involved in an intensive study of the reproductive system. With the cyclic use of .5 mg chlormadinone acetate there were 2 pregnancies on of which was due to failure of the patient to continue the regimen. The principal side effect was intramenstrual bleeding and spotting in about 20-25% studied. Endometrial biopsies showed that the drug did not prevent the development of a normal secretory endometrium this was seen in 80 of the 109 specimens. Of 122 urinary pregnanediol determinations done 33(27%) had concentrations at ovulatory levels. In culdoscopic findings follicular activity or corpora lute were found in 18 of 19 patients studied. Contraceptive protection was also afforded with continuous administration of the drug. With continuous administration of the drug approximately 60% of the women had cycles of 24-34 days the longer cycle being more common and 80-90% had 7 or less days of bleeding per month. The endometrium showed less evidence of normal secretory activity than that seen with cyclic administration of the same drug. Preliminary studies of ovarian biopsy specimens suggest that ovulation occurs as in cyclic treatment.

A clinical study with continuous low doses of megestrol acetate for fertility control.

Abstract Dose response, contraceptive efficacy, and menstrual cycle control were tested in 667 normal fertile women using daily oral administration of megestrol acetate (MA) in either an oil solution or a tablet form. The occurrence of a regular menstrual bleeding pattern suggests that the hypophyseal-ovarian-uterine axis was not altered to any great degree. Contraceptive effectiveness was related to the type of formulation as well as to the dosage of the progestogen. The oil solution of MA proved to be more effective than the same dosage in tablet form.

Sustained release hormonal preparations: X. Uptake of 6-methyl-17α-acetoxy-4,6-pregnadiene-3, 20-dione released from polydimethylsiloxane implants by various tissues of male and female rats

Abstract Plasma levels and uptake by various tissues of 6-methyl-17α-acetoxy-4,6-pregnadiene-3,20-dione and metabolites released from polydimethylsiloxane implants were compared in female and male rats. In females circulating levels 4 days after implantation were 3120 ng 100 ml of plasma; in males the corresponding value was 2790 ng 100ml . The uptake by the hypothalamus, cerebellum, pituitary, adrenals, liver and body fat was higher in female animals than in male animals. Estrone treatment of males influenced uptake in the liver, adrenals and fat but not in the other organs.