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High dose medroxyprogesterone acetate (MPA) treatment in metastatic carcinoma of the breast: a dose-response evaluation.

The results of controlled clinical trial that used high doses of medroxyprogesterone acetate (MPA) in the treatment of metastatic breast cancer are reported. Two treatment reigmens were used: regimen A, 500 mg daily with a total dose of 30 g; regimen B, 1,000 mg daily with a total dose of 60 g. The overall response rates were similar, with no statistically significant difference between the two treated groups. Regimen A (lower dosage group) reached a remission rate of 44%, whereas regimen B (higher dosage group) had a remission rate of 41%. The mean duration of response was 8 months with regimen A and 9 months with regimen B. The advantages of the lower dosage regimen as opposed to the higher dosage regimen of MPA in the treatment of advanced breast cancer are discussed.

Abscess↗

Sustained effects on synthetic ovarian steroids of rat myometrial contractility.

Ovariectomized rats were given a single dose of synthetic oestrogen or progestogen, or both combined. On selected days after treatment one rat from each treatment group was killed and myometrical contractility in response to spasmogens was measured isometrically in isolated tissue baths. Contractility persisted at a low level after ovariectomy without steroid replacement (controls) for the 60 days of the experiment. The powerful potentiating action of oestrogen reached a maximum in about 10 days and sustained a high level thereafter. Progestogen treatment did not influence contractility to a significant degree when compared with saline, except that the contractions were sometimes of higher frequency and more irregular in size. There was a less powerful potentiating action on contractility with combined oestrogen and progestogen treatment than with oestrogen alone. It reached a maximum in 4 days and declined more rapidly than with oestrogen-treated preparation but was still vigorous for up to 30 days.

Acetylcholine↗

Serum follicle-stimulating hormone, luteinizing hormone and progesterone concentrations in pseudopregnant rats treated with medroxyprogesterone acetate.

Pseudopregnant rats were treated early in pseudopregnancy with 1 or 10 mg medroxyprogesterone acetate (MPA). Serum FSH, LH and progesterone concentrations were determined on days 2-20 of pseudopregnancy in treated and control rats. The mean duration of pseudopregnancy was 13-5 days in the control animals, but when animals were treated with 1 mg MPA a dioestrous period of 21-4 days was observed. A period with leucocytic vaginal smears of at least 2 months was observed after treatment with 10 mg MPA. Injection with MPA on day 3 of pseudopregnancy did not affect the serum FSH concentrations during the subsequent days. The progesterone pattern was alike in the three groups of animals, i.e. the duration of the activity of the corpora lutea was similar in all groups. However, 10 mg MPA slightly lowered progesterone concentrations on days 4-8 of pseudopregnancy. In the saline-treated rats, LH concentrations decreased from days 2-5, and remained low until they increased after day 11 of pseudopregnancy. This increase was delayed until day 20 in the animals treated with 1 mg MPA, and was not observed in the animals treated with 10 mg MPA. It is argued that the increase of LH concentration at the end of pseudopregnency is not instrumental in the decrease of peripheral progesterone concentration but rather that the decrease in the progesterone concentration leads to the increase in the LH concentration.

Animals↗

Effect of medroxyprogesterone acetate contraception on cytoplasmic estrogen receptor content of the human cervix uteri.

Specimens of cervical tissue from five women each on 150 mg and 450 mg regimens of medroxyprogesterone acetate (MPA) for contraceptive purposes, were obtained through punch biopsy 15 days after injection. In another group of five women each on the same contraceptive regimens, punch biopsies of the cervix uteri were obtained 30 days after injection. These times corresponded to maximum and optimum blood levels of MPA respectively. Corresponding tissue from the same anatomical position in patients matched, where possible, for age and parity was obtained from hysterectomy specimens to serve as controls. Quantification of estrogen receptor content in the cytoplasm of these tissues was achieved through standard procedures. Analysis of data showed that MPA suppressed estrogen receptor content significantly compared to controls, but that there were no differences in this effect between the two dosages or time of biopsy.

Adult↗

Pure crystalline estradiol pellet implantation for contraception.

The subcutaneous implantation of estradiol pellets was found to be a simple and effective contraceptive method with good patient acceptance and minimal untoward effects. The pellets (25 mg each) were implanted through a Kearn's trocar into the abdominal wall, 2.5 to 5 cm above and parallel to Poupart's ligament. The regimen began with four pellets, and the dose was maintained or decreased by one pellet every 6 months (four, three, two, one). A potent progestogen was utilized monthly for induction of withdrawal bleeding. Altogether, 236 patients were followed for a total of 1,060 courses in 6,360 cycles (489,02 woman-years). Two pregnancies occurred during therapy. Pearl's index was 0.37. No significant alterations occurred in body weight and blood pressure. Glucose tolerance test, standard blood profiles, and Papanicolaou smears were normal during therapy. No cases of thrombophlebitis, blurred vision, headaches, gastric symptoms, or amenorrhea-galactorrhea were observed. The suppression of ovulation was confirmed by endometrial biopsies, basal body temperature, and serum follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone in a selected group of patients.

Abdominal Muscles↗

[Six-monthly administration of medroxyprogesterone acetate (MPA) (author's transl)].

For more than six years the authors have studied the acceptability and the effectiveness of Medroxyprogesterone Acetate (450 mg) as a long acting contraceptive (six months). With a Pearl index of 0.85, the method was considered as effective whereas its acceptability was adversely influenced by the bleeding irregularities that take place during the first year of use. A good patient-doctor relationship could lessen this influence.

Drug Administration Schedule↗