IPPF survey: world's contraceptors increased by 35 million; 5 million more in F.P. programs.
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After 4 years of a long-term contraceptive steroid safety study, the incidence and the histologic types of mammary dysplasia produced are shown to be similar in beagles treated with medroxyprogesterone acetate (medroxyprogesterone) or progesterone. Serum insulin, thyroid-stimulating hormone (TSH), triiodothyronine, growth hormone, prolactin, 17 beta-estradiol, progesterone, and cortisol were determined by radioimmunoassay on samples collected after 45 months of treatment. Serum growth hormone and insulin concentrations were elevated in a dose-related manner in both treatment groups. Levels of triiodothyronine, cortisol, and 17 beta-estradiol (medroxyprogesterone only) were lowered. TSH and prolactin concentrations were not changed. Pituitary-gonadal hormone interaction in the pathogenesis of mammary neoplasia of the dog is discussed. Prolonged treatment of beagles with doses of progesterone or medroxyprogesterone 1 to 25 times the human contraceptive dose or luteal phase (dog) levels, respectively, results in a dose-related incidence of mammary nodules.
The effect of high-dose medroxyprogesterone acetate (MPA, 250 mg intramuscularly for six days) on hepatic drug-metabolism and liver function was investigated in eleven females with endometrial carcinoma. Antipyrine plasma clearance, an index of hepatic drug-metabolizing ability, improved significantly during this treatment, and the serum total bilirubin level was lowered, whereas other liver function tests, including alkaline phosphatase, and albumin values in the serum, remained unchanged. The results demonstrate that therapy with MPA has an inducing effect on hepatic enzyme activity and antipyrine metabolism. The findings may be of importance when prescribing drugs for females receiving large doses of MPA.
The treatment of normal male dogs with a depot preparation of medroxyprogesterone acetate (4 mg/kg) for 7 weeks reduced peripheral testosterone levels by 58%. No effects on testicular size and consistency, semen quality or libido were found.
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The effect of long term treatment with estrogens alone or along with medroxyprogesterone acetate on the Leydig cell ultrastructure was studied in testes from males undergoing surgery for sexual reassignment. The testes were fixed for electron microscopy by a perfusion method to insure uniform preservation. The morphological features were not the same in all the treated testes. Therefore, the cells found in the intertubular region were classified into three groups: (A) Leydig cells very similar to controls; (B) Absence of typical Leydig cells, but with cells having increased microfilaments, abundant smooth endoplasmic reticulum and some lipid droplets; (C) Absence of any cell type possessing abundant smooth endoplasmic reticulum, but having varying amounts of microfilaments and pigmentation. It is suggested that some of the cell types found in the intertubular region are dedifferentiated Leydig cells. This study indicates that the human testis from transsexuals of reproductive age is an appropriate model to study the indirect and direct effects of estrogens on the ultrastructure of cell types found in the human testes.
The continuation contraceptive practise of 3,293 I.U.D., 1985 pill and 749 depo-provera acceptors was analysed by a survey of family planning records. The proportions of grand multiporae were 40.3%, 24.2% and 40.4% in the three groups. Pap smears were taken in from 12 to 38.5% of acceptors and the proportions of pathological smears varied from 8.9 to 13.3%. The percentages of acceptors who attended only once more were 11% (I.U.D.), 18.1% (pill) and 25.1% (d-p.), Pregnancy rates were for the I.U.D., 1.7 per Hundred Woman Years, for the 2.1 per H.W.Y. and for d-p, 0.4, per H.W.Y. Temporary interruptions of the contraceptive methods were common with the pill and d-p. In the long run the I.U.D. is superior to the other temporary methods of contraceptives. Continuation rates with the I.U.D. were 89.9% after one year and 70.9% after five years (similar rates for the pill were 55% and 16.5% and for d-p 50.5% and 10.3%). The importance of a proper pelvic examination and the need to have all methods available for any individual receiving contraceptives are emphasized in the discussion. Tubal ligations should always be considered as an alternative to the temporary methods of contraceptives in ground multiporae and others at special risk from further pregnancies.
The inhibitory effect of some gestagens and calusterone on the binding of oestradiol-17beta to its specific uterine receptors has been investigated in intact rats. Progesterone, medrogestone, clogestone, medroxyprogesterone acetate and calusterone reduce the specific oestradiol-receptor interaction in vitro; this effect is dose-dependent and does not differ significantly from one drug to the other. A more relevant decrease in the amount of oestradiol-17beta bound to specific receptors has been observed with calusterone. Progesterone, clogestone, medrogestone, medroxyprogesterone acetate and calusterone given orally induce a marked decrease (between 30 and 70% depending on the dose) in the binding capacity of oestradiol-17beta to specific uterine receptors in vivo. Results from a Scatchard plot analysis suggest that the interference with the binding of oestradiol-17beta caused by both progestogens and calusterone is due to a non-competitive interaction.
The radioisotopic method of 131J-labelled albumin was employed to determine the distribution of acidic proteinase activity in some organs and tissues of chickens. The highest enzymatic activities were found in intestine wall, in pancreas, and in liver. Considerably lower activities were ascertained in kidneys, brain, lungs, and heart. The different proportions of these enzymes in homogenates and supernatant fractions (106 000 g) testify to a lack of uniformity in the solubility of cathepsins in the organs tested. The tested organs, with the exception of pancreas, did not show any enzymatic activity of neutral proteinases.
Radioimmunoassays for 2 synthetic progestins (Ethinyl-norgestrienone, R 2323 and medroxyprogesterone acetate, MPA) are demonstrated. 10 patients aged 31 to 72 years were treated with ethinyl-norgestrienone with different schedules and 3 men suffering from benign prostatic hypertrophy were treated with medroxygesterone acetate. Plasma levels of testosterone, LH, FSH were monitored before, during and after treatment.
Medroxyprogesterone acetate is a steroid compound similar to progesterone in structure and function. Thirty women were given 150 mg. of medroxyprogesterone intramuscularly, and samples of the endometrium were examined by light and electron microscopy. The initial response of normal human endometrium was maturation and then inhibition. By 50 days after injection, the atrophic changes began to reverse, and by Day 90, after injection the tissue resembled normal proliferative endometrium. A previously undescribed nuclear inclusion body is present; however, its significance is unclear at this time. On the basis of ultrastructural changes, medroxyprogesterone appeared not to exert a significant influence on the endometrium past 90 days at this dosage.
A study was performed to obtain additional information about the effects of oral contraceptives on pituitary function. A sequential pituitary stimulation test (SST) was used to study normal control women who then received either a combination pill with 50 mug of ethinyl estradiol or an injectable or oral progestin for three weeks, after which the test was repeated. The same test was also performed on five long-term oral contraceptive users. The SST consists of measurement of growth hormone (GH), thyroid-stimulating hormone (TSH), prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) at frequent intervals after stimulation by hypoglycemia, thyrotropin-releasing hormone, and gonadotropin-releasing hormone. GH and TSH release following stimulation were unaffected by the use of contraceptive steroids, while PRL release was increased by both the combination pill and the progestin alone. LH and FSH release was decreased in the three short-term and most of the long-term users of the combination pills but was not decreased in two of the long-term users as well as in those receiving the progestin alone. These results indicate that the combination oral contraceptives have a direct effect upon the pituitary gland, causing an increase in prolactin release and a decrease in gonadotropin release. This effect varies among individuals receiving the same formulation and may be related to the development of syndrome of postpill amenorrhea-galactorrhea.
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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.
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.
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.