The effect of monthly depot medroxyprogesterone acetate and testosterone on human spermatogenesis. II. High initial dose.
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OBJECTIVE: To assess whether women who were administered the first injection of DMPA+E(2)C on day 7 of their menstrual cycle (delayed injection) exhibit the same degree of ovarian suppression as women who receive it on day 5 of their menstrual cycle. DESIGN: Multicenter, randomized controlled trial. SETTING: Reproductive health clinics. PATIENT(S): Women aged between 18 and 38 years (inclusive) willing to use DMPA+E(2)C as their method of contraception. INTERVENTION(S): Participants received a DMPA+E(2)C injection on day 5 (control group, n = 41) or day 7 (delayed-injection group, n = 117) of their menstrual cycle. MAIN OUTCOME MEASURE(S): Ovarian activity and follicular development determined by serial serum progesterone levels and vaginal ultrasound. RESULT(S): Participants who received DMPA+E(2)C on day 5 of their menstrual cycle (control group) exhibited no more than limited follicular growth (no follicle >16 mm). Of those women who received DMPA+E(2)C on day 7 of their menstrual cycle (delayed-injection group), 21 (18%) showed some follicular growth, of whom 4 (3%) ovulated. CONCLUSION(S): The first injection of DMPA+E(2)C given on day 7 of a menstrual cycle does not provide the same inhibition of ovarian activity as that observed when it is administered on day 5 of the menstrual cycle.
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In previous papers we have demonstrated that sialoadenectomy inhibited MPA-induced mammary tumorigenesis in BALB/c mice. To further explore the role of EGF in this experimental model, we evaluated its effects on mammary glands of sialoadenectomized (sialox) MPA-treated female mice and on tumor growth. MPA-treated sialox mice were injected s.c. (n = 3) or not (n = 6) with 5 microg EGF every 36 h for 45 days; MPA-treated sham-operated mice were used as controls (n = 6). Mammary glands from sialox MPA-treated mice are considerably less developed as compared with sham-operated animals. The exogenous administration of EGF restores the usual MPA-induced growth pattern of the glands, thus confirming a role for EGF either in mediating or cooperating with MPA in inducing the mammary architectural changes observed in MPA-treated mice. On the other hand, primary cultures of progestin-dependent (PD) ductal mammary adenocarcinoma in vivo tumor lines and of lobular progestin-independent (PI) tumor lines were used to evaluate the effect of EGF on tumor growth. In vitro EGF was found to stimulate cell proliferation of lobular PI tumor cells and of fibroblastic cells from both types of tumors at concentrations higher than 0.1-0.5 ng/ml and in the presence of 1-5% of charcoal-stripped fetal calf serum. Conversely, no proliferative effects were observed in ductal PD cells under the same experimental conditions, regardless of the presence of 10 nM MPA. It can be concluded that although EGF plays an important role in MPA-induced mammary carcinogenesis, it is not necessary in PD tumor growth.
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OBJECTIVES: We sought to compare the effects of estrogen/transvaginal progesterone gel with estrogen/medroxyprogesterone acetate (MPA) on exercise-induced myocardial ischemia in postmenopausal women with coronary artery disease or previous myocardial infarction, or both. BACKGROUND: Estrogen therapy beneficially affects exercise-induced myocardial ischemia in postmenopausal women; however, women with an intact uterus also take progestin to protect against uterine malignancies. The effects of combination estrogen/progestin therapy on myocardial ischemia are unknown. METHODS: Eighteen postmenopausal women (mean +/- SD age 59+/-7 years) were given 17-beta-estradiol in single-blinded manner for four weeks (1 mg/day for three weeks then 2 mg/day for one week). Estradiol (2 mg/day) was then continued, and the patients were randomized (double-blind) for 12 days to either transvaginal progesterone gel (90 mg on alternate days) and oral MPA placebo (10 mg/day), or vice versa. After another two weeks on estradiol alone, the patients crossed over to progestin treatment and repeated the protocol on the opposite treatment. Patients underwent treadmill exercise testing after each estradiol phase and at day 10 of each progestin phase. RESULTS: Exercise time to myocardial ischemia increased after the first estrogen phase as compared with baseline (mean difference with 95% confidence interval [CI]: 72 s [34 to 110], p = 0.001), and was increased by combination estradiol/progesterone therapy as compared with estradiol/MPA therapy (92 s [35 to 149], p = 0.001)). Two patients (11%) were withdrawn while taking estradiol/MPA owing to unstable angina. CONCLUSIONS: Combination estrogen/transvaginal progesterone gel increases exercise time to myocardial ischemia, as compared with estrogen/MPA. These results imply that the choice of progestin in women at higher cardiovascular risk requires careful consideration.
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