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[A comparative study between low-dose and high-dose medroxyprogesterone acetate (MPA) in the treatment of advanced and recurrent breast cancer--in relation to dose, serum concentration and response. Osaka Breast Cancer Research Group].

A prospective randomized study was carried out to evaluate the effectiveness of MPA in the treatment of breast cancer by comparing low dose (600 mg/day) with high dose (1,200 mg/day) of MPA. In 35 evaluable cases, the response rate to treatment was 40.0% (8/20) with low dose MPA and 26.7% (4/15) with high dose MPA. There was no significant difference between the two groups. The serum MPA concentration measured by high-performance liquid chromatography (HPLC) assay was 23.2 +/- 17.6 ng/ml in the low-dose group and 89.5 +/- 56.7 ng/ml in the high-dose group. Intrapatient variability in serum MPA concentration was relatively stable, but interpatient variability was large. No correlation was found between the response rate and serum MPA concentration. The above results indicate that a low dose of MPA (600 mg/day) is a useful treatment with high effectiveness and safety in advanced and recurrent breast cancer patients. Though no exact data on the optimal serum concentration could not be obtained, it was obvious that a successful response cannot be expected from a serum MPA concentration of less than 17 ng/ml, which was the average serum concentration in NC and PD patients of the low-dose group.

Adult↗

Medroxyprogesterone acetate in the treatment of obstructive sleep apnea.

The use of MPA in patients with OSA is limited. Instead, patients with OSA should be encouraged to abstain from alcohol and respiratory depressive agents, and avoid sleeping in the supine position. In general, patients with OSA are most effectively treated with CPAP and/or surgery. Patients need to be encouraged to maintain ideal body weight, since this has been associated with a marked reduction in symptoms. For patients who are not surgical candidates or refuse to use CPAP, drug therapy may be beneficial. Fluoxetine has been shown to be as effective as protriptyline, and is better tolerated. However, further study is needed to determine whether selective serotonin-reuptake inhibitors are beneficial in treating OSA. Therefore, MPA therapy should be reserved for hypercapnic patients who refuse other modalities of treatment. The potential long-term adverse effects of MPA must be addressed before initiating therapy in men with OSA.

Humans↗

Effects of levonorgestrel, medroxyprogesterone acetate, norethindrone, progesterone, and 17beta-estradiol on thrombospondin-1 mRNA in Ishikawa cells.

Abberant endometrial angiogenesis has been implicated in abnormal endometrial bleeding in users of progestin-only contraceptives. We believe that a possible cause is an underexpression of thrombospondin-1 (TSP-1). Progestins had less effects on TSP-1 mRNA compared to P, in Ishikawa cells, and this difference in TSP-1 expression by individual progestins may be associated with the irregular bleeding seen in women using progestin-only contraception.

Cell Line↗

Adjuvant chemo-hormonal therapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) with or without medroxyprogesterone acetate (MPA) for node-positive cancer patients, update at 12 years follow up.

An update with 10 years of follow up of a study adding adjuvant MPA to CAF chemotherapy is presented. A total of 409 patients were entered, of which 200 were randomized to receive 500 mg of MPA i.m. on days 1-28 and twice per week thereafter for 6 months. There was a significant improvement in metastases-free and overall survival in women >60 years of age receiving MPA (P=0.01 and P=0.02 respectively). A detrimental effect of MPA was seen in women <40 years. Possible reasons for these results are discussed.

Clinical Trial↗

Steroid receptors and mammalian penile development: an unexpected role for progesterone receptor?

PURPOSE: We investigated the role of steroid receptors in normal and abnormal genital tubercle development in males and females. We hypothesized that progesterone receptor expression might be involved in abnormal development in both sexes. MATERIALS AND METHODS: We examined the effects of medroxyprogesterone acetate on steroid receptor mRNA expression and assessed the involvement of androgen receptor in the action of medroxyprogesterone acetate on genital tubercle development using androgen receptor deficient (Tfm) mice. RESULTS: Quantitative reverse transcriptase polymerase chain reaction and morphological results demonstrated a pattern of virilized females and feminized males in medroxyprogesterone acetate exposed embryos. Progesterone receptor was the only steroid receptor examined that did not differ between medroxyprogesterone acetate treated males and vehicle treated females. At the morphological level in utero exposure to medroxyprogesterone acetate from gestational days 12 to 17 feminized male genital tubercles, producing a more proximal urethral opening. Female fetuses exposed for the same period exhibited virilized genitalia, with a more distal urethral opening. We also exposed Tfm mice to medroxyprogesterone acetate to assess the role of androgen receptor in the activity of medroxyprogesterone acetate. These medroxyprogesterone acetate exposed mice did not differ morphologically from vehicle treated Tfm mice, indicating that medroxyprogesterone acetate requires androgen receptor to elicit genital tubercle abnormalities. CONCLUSIONS: The increase of progesterone receptor mRNA expression in males and the decrease in females as a result of exposure to medroxyprogesterone acetate, which also causes urethral abnormalities in both sexes, suggests a previously unidentified role for progesterone receptor, possibly interacting with androgen receptor, in anomalous genital tubercle development.

Animals↗

Postpartum contraceptive use among adolescent mothers.

OBJECTIVE: To compare the incidence of repeat pregnancy and method continuation rate at 12 months postpartum in young women who chose either depot medroxyprogesterone acetate or oral contraceptives (OCs) as contraception. METHODS: We conducted a prospective cohort study of 122 postpartum women younger than 18 years of age who delivered between January 8, 1997 and December 31, 1997. Patients choosing depot medroxyprogesterone acetate (n = 76) and OCs (n = 46) were accrued for 12 months and were followed-up for a minimum of 12 months. Main outcome measures were median contraceptive method continuation and the incidence of repeat pregnancy at 12 months postpartum. RESULTS: There was no difference in mean age at delivery (P =.47), parity (P =.84), or gravidity (P =.78) between depot medroxyprogesterone acetate and OC users. At 12 months postpartum, 27.4% of OC users and 55.3% of depot medroxyprogesterone acetate users were still using contraception. Median time to contraceptive discontinuation was longer for those choosing depot medroxyprogesterone acetate compared with OCs (17.8 vs 7.4 months, respectively, P =.002). The overall incidence of repeat pregnancy at 12 months postpartum was 10.6%. Among OC and depot medroxyprogesterone acetate users, respectively, 24% and 2.6% became pregnant again, producing a relative risk (RR) of 9.09 (95% confidence interval [CI] 2.1, 39.2) for repeat pregnancy among OC users. The mean time to repeat pregnancy (this was reported instead of the median time whenever the pregnancy rate had not reached 50% at the end of the follow-up period) was longer for depot medroxyprogesterone acetate compared with OC users (17.1 months vs 13.2 months, respectively, P <.001). CONCLUSION: Adolescent mothers using depot medroxyprogesterone acetate injection for contraception have a higher method continuation rate and a lower incidence of repeat pregnancy at 12 months postpartum than those selecting OCs during the same period.

Adolescent↗