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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

Long-term effects of depot-medroxyprogesterone acetate on lipoprotein metabolism.

To assess the effects of depot-medroxyprogesterone acetate (DMPA) upon serum lipids and lipoproteins, a comparative study in chronic users and new acceptors was undertaken. Two groups of women of reproductive age were included in the study; group I (n = 8) was formed by new acceptors whereas, group II (n = 14) constituted DMPA users of more than five continuous years (7.0 + 2.1 years). Blood samples were taken on the day of injection and 15, 29, 57 and 92 days after the i.m. administration of 150 mg of DMPA for the measurement of total triglycerides (TG), cholesterol (CHOL) and phospholipids (PHL). In addition, the TG and CHOL content in the very low density (VLDL), low density (LDL) and high density (HDL) lipoprotein fractions obtained by ultracentrifugation were also determined. The results demonstrated a moderate increase in the serum total TG concentrations at the expense of the VLDL fraction in the group of chronic DMPA users. In both groups, the administration of DMPA induced a moderate, though not significant, decrease in total CHOL and HDL-chol, an effect that was noticed at the end of the treatment interval; the serum LDL-chol content remained unchanged. In addition, a decrease in the total serum phospholipids content was noticed after DMPA injection in both groups, which resembled the fluctuations observed in the luteal phase of normal ovulating women. The overall data indicate that acute and/or chronic DMPA administration at the dose currently employed for contraception does not induce major abnormalities in lipoproteins in serum.

Adult

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

A comparison of medroxyprogesterone serum concentrations by the oral or intramuscular route in patients with persistent or recurrent endometrial carcinoma.

A randomized study, comparing serum medroxyprogesterone concentrations by the oral and intramuscular routes, was performed on 22 patients with persistent or recurrent endometrial adenocarcinoma by six institutions of the Gynecologic Oncology Group. The oral group (11 patients) received cutaneous Provera (medroxyprogesterone), 50 mg three times a day, and the intramuscular group (11 patients) received 300 mg of Depo-Provera (medroxyprogesterone) weekly for at least 2 months. Serum levels were evaluated at 0, 2, 4, 6, 8, 10, and 12 hours after administration and every day for the first week and weekly thereafter for 8 weeks. The mean serum levels (nanograms per milliliter) of medroxyprogesterone in the oral group were consistently higher than the corresponding mean levels of the intramuscular group. In addition, from the first through eighth weeks, the measurements (medians) for the oral group were statistically higher than those for the intramuscular group. Although the study indicates a significant increase in serum levels achieved by the oral route, the follow-up period of patients under study is too early to evaluate its clinical effectiveness as compared to the intramuscular route.

Adenocarcinoma

Serum medroxyprogesterone acetate (MPA) concentrations and ovarian function following intramuscular injection of depo-MPA.

A sensitive radioimmunoassay measuring serum medroxyprogesterone acetate (MPA) has been developed in order to measure and correlate serum MPA concentrations and ovarian function in women following im administration of deop-MPA (DMPA), employing goat anti-MPA-3-(O-carboxymethyl) oxime-bovine serum albumin and MPA-3-(O-carboxymethyl) imino-125I-iodohistamine. In the 3 women studied, im injection of 150 mg of DMPA yielded brief initial serum MPA concentrations ranging from 1.5 to 3 ng/ml for a few days. Serum MPA concentrations gradually declined and remained relatively constant at about 1 ng/ml for 2 to 3 months, declined gradually thereafter reaching 0.2 ng/ml during the 6th month and became undetectable (less than 0.02 ng/ml) about 7-1/2 to 9 months following administration. Serum estradiol remained at early to midfollicular phase levels for 4 to 6 months after DMPA injection and rose to preovulatory levels when serum MPA levels fell below 0.5 to 0.25 ng/ml. Ovulation, however, as evidenced by serum progesterone concentrations did not occur, apparently due to suppression of the LH peak by positive feedback inhibition. Prolonged inhibition of cyclic ovarian function following DMPA injection is caused by slow MPA absorption and persists until serum MPA levels have decreased below 0.1 ng/ml or become undetectable about 7 to 9 months after DMPA administration.

Adult

Endometrial histology and circulating levels of medroxyprogesterone acetate (MPA), estradiol, FSH and LH in women with MPA induced amenorrhoea compared with women with secondary amenorrhoea.

Circulating levels of medroxyprogesterone acetate (MPA), estradiol, progesterone and gonadotropins were determined in 11 women on long-term treatment with depot-MPA (Depo-Provera DMPA) 150 mg i.m. every 12th week as a contraceptive. The women had amenorrhoea due to the treatment. Endometrial biopsy was performed one week after injection and at the end of the 12 week period. Blood samples were taken on the same occasions. The findings were compared with those in 12 untreated women having secondary amenorrhoea. MPA was still detectable in serum and the end of the 12 week period. Endometrial biopsies showed gestagenic effects in the second as well as in the first biopsy. No MPA was detectable in the untreated women with amenorrhoea, and no gestagenic effects could be demonstrated in their biopsies. The estradiol levels in the DMPA group were in the range of the early follicular phase of a normal menstrual cycle and showed a significant rise at the end of the 12 week period. On the last sampling occasion the estradiol levels did not differ from those in the untreated women with secondary amenorrhoea. The levels of progesterone and gonadotropins were in the range of the early follicular phase in both groups. These observations support that DMPA 150 mg i.m. every 12th week is a depotpreparation with prolonged effect, and inhibits ovulation and produces endometrial changes by means of biologically active serum concentrations throughout the 12 week period.

Adult

Plasma medroxyprogesterone acetate levels following intramuscular or oral administration in patients with endometrial adenocarcinoma.

The concentration of medroxyprogesterone acetate (MPA) in plasma samples taken 24 h after intramuscular or oral administration of 100 mg daily doses of the drug to patients with endometrial adenocarcinoma was measured by radioimmunoassay. In general, a plasma level of about 4 ng/ml was found 24 h after the dose, independent of the route of drug administration. However, in three of the patients to whom intramuscular MPA was given, considerably higher values were found. A maximal plasma level was achieved three hours after ingestion of 100 mg MPA. This was followed by a rapid decline to 20-25% of the peak value after about 12 h. A rather small day-to-day intraindividual variation was found in daily blood samples taken just before administration of the next dose. However, considerable differences were found between individuals and it is concluded that this variation in plasma levels may be reflected in the clinical efficacy of the treatment. Thus further studies in which plasma values and clinical effectiveness are correlated seem to be indicated.

Adenocarcinoma