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[Concentration of estrone, estradiol and estriol in the blood of pregnant sheep after induction of estrus with chlormadinone acetate and medroxyprogesterone acetate].

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.

Animals↗

Radioimmunoassays of ethinyl-norgestrienone (R-2323) and medroxyprogesterone acetate (MPA) and their clinical applicability.

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.

Adult↗

The ultrastructural response of human endometrium to medroxyprogesterone acetate.

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.

Adult↗

The effect of contraceptive steroids on hypothalamic-pituitary function.

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.

Contraceptives, Oral↗

Radioimmunoassay of serum medroxyprogesterone acetate (Provera) in women following oral and intravaginal administration.

A radioimmunoassay (RIA) method for measuring medroxyprogesterone acetate (MPA, Provera) in serum has been developed utilizing benzene:iso-octane extraction, 3H-MPA to assess procedural losses, goat anti-MPA-3-(0-carboxymethyl) oxime-bovine serum albumin serum and dextran-coated charcoal separation. Control serum blanks were undetectable, 200 pg/ml of MPA was measurable with a high reliability, and intra- and interassay coefficients of variation were 6 and 13 percent, respectively. MPA added to control serum was quantitatively recovered. Serum MPA levels measured in 2 women after ingestion of 10 mg MPA rose to 3.4 to 4.4 ng/ml within 1 to 4 hours after oral intake and fell rapidly thereafter to 0.3 to 0.6 ng/ml within 24 hours. Insertion of Silastic intra-vaginal rings (IVRs), containing 100 or 200 mg of MPA, into 4 women for periods of 3 weeks resulted in a rapid rise of serum MPA after insertion, rather stable MPA levels of 0.9 to 1.6 ng/ml while the IVRs were in place, and a rapid decline of serum MPA following IVR removal. Serum estradiol-17beta and progesterone concentrations, measured about 3 times a week in these patients, indicated that ovulation was consistently inhibited. The serum MPA levels observed in this study were approximately 5 times lower than those reported by other investigators using a double-antibody RIA of MPA in unextracted serum.

Administration, Oral↗

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↗