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A new combination of conjugated equine oestrogens and medroxyprogesterone for treatment of climacteric complaints.

Thirty-four post-menopausal women with climacteric complaints were given conjugated equine oestrogens (1.25 mg/day) for 21 days followed by 2 days without hormones and then 5 mg medroxyprogesteroneacetate daily for 5 days. The present trial was designed to study effects on vasomotor symptoms, bleeding patterns and endometrial histopathology. Vasomotor disturbances were completely relieved. No recurrence of symptoms was recorded in the oestrogen-free week. Withdrawal bleedings were regular and slight, which was a positive experience for those women who had previously been treated with other oestrogen-progestogen regimens. In most patients inactive or weak secretory endometrial epithelium was found during treatment. Two women developed differing degrees of hyperplasia after 2.5 and 3 yr, respectively. This fact emphasizes the necessity of adding progestogens for at least 10 days each month even if the oestrogens and progestogens are administered separately. It may also be wise to perform an endometrial biopsy when sex hormones are administered on a long-term basis.

Biopsy↗

Transdermal estradiol plus oral medroxyprogesterone acetate replacement therapy in primary amenorrheic adolescents. Clinical, hormonal and metabolic aspects.

Twelve primary amenorrheic adolescents were treated with transdermal estradiol 100 micrograms (Estraderm TTS-100 (R)) twice weekly for 3 weeks, plus MPA 10 mg per os daily (Provera) for the last 11 days, following an interval of 1 week. A basic examination and a re-examination at 6- and 12-month intervals were carried out for clinical evaluation, hormonal assays, lipid, carbohydrate and bone metabolism. No significant changes were recorded on the FSH, LH, 17 beta-estradiol and PRL serum levels. A significant decrease of TC values and atheromatic indices 1 (TC/HDL) and 2 (LDL/HDL) was seen (P < 0.05) at the end of treatment. On the other hand a significant increase in apolipoproteins A1 was found. A beneficial effect was also recorded on the bone mass. Finally, no significant side-effects were reported. It is concluded that this kind of hormone replacement therapy is efficient and safe for the treatment of amenorrheic adolescents due to gonadal dysgenesis.

Administration, Cutaneous↗

Norgestimate and medroxyprogesterone acetate do not attenuate the atheroprotective effects of 17beta-estradiol in ovariectomized, apolipoprotein E-deficient mice.

OBJECTIVE: To determine whether progestins counteract the cardioprotective effects of estrogen. DESIGN: Controlled animal study. SETTING: Academic laboratory environment. ANIMAL(S): Female apolipoprotein E-deficient mice. INTERVENTION(S): Mice were randomly assigned to groups receiving a sham operation plus placebo pellet, bilateral gonadectomy plus placebo pellet, or gonadectomy plus one of nine combinations of estrogen/progestin SC pellets. MAIN OUTCOME MEASURE(S): Total plasma cholesterol, body weight, fat depot weight, uterine weight and size, and the cross-sectional area of fatty streaks in the aortic sinus were measured in each animal. RESULT(S): After 8 weeks of treatment, plasma cholesterol levels were significantly higher only in the ovariectomized and sham-operated animals that received placebo pellets. No differences in plasma cholesterol were observed relative to the type or amount of progestin administered. There was a reduction in fatty streaks in all of the hormone treatment groups as compared with both the ovariectomized and sham-operated animals that received placebo pellets. CONCLUSION(S): There were no significant differences in lesion area in response to estrogen alone or to estrogen plus the different types and doses of progestins.

Adipose Tissue↗

Relief of vasomotor symptoms and vaginal atrophy with three doses of conjugated estrogens and medroxyprogesterone acetate in postmenopausal Asian women from 11 countries: The Pan-Asia menopause (PAM) study.

OBJECTIVE: To evaluate the efficacy of three doses of estrogen/progestin therapy for relief of vasomotor symptoms (VMS) and vaginal atrophy in Asian women of different ethnic background; to examine differences in prevalence of VMS among ethnic groups. METHODS: A prospective, randomized, double-blind multinational clinical trial in healthy postmenopausal women from 11 Asian countries. Following 2 weeks of baseline observations, the women received one of three conjugated estrogens (CE)/medroxyprogesterone acetate (MPA) doses (in mg) daily for 24 weeks: 0.625/2.5; 0.45/1.5; or 0.3/1.5. The women recorded VMS and uterine bleeding daily on diary cards translated into 10 languages. Vaginal responsiveness was evaluated by the vaginal maturation index (VMI) at baseline and at week 24. RESULTS: The study population consisted of 1028 postmenopausal women. The VMS-evaluable subpopulation was about 60% of the total population. The mean baseline hot flush frequency was 1.6 flushes/day (613 women). Hot flush frequency decreased significantly in all dose groups within 4 weeks of treatment. The VMI shifted significantly from immature (parabasal) to mature (superficial) cells at end of treatment. The therapeutic responses were comparable in all three groups. However, uterine bleeding was consistently less frequent in the 0.3/1.5 mg group. The percentage of women who reported VMS at baseline differed substantially among the different ethnic groups, ranging from 5% in Indonesian women to 100% in Vietnamese women. CONCLUSION: Asian postmenopausal women respond to CE/MPA therapy. The lowest dose is as effective for VMS and vaginal responsiveness as the higher doses, and the lowest dose is associated with the most favorable bleeding pattern. The prevalence of vasomotor symptoms differs among ethnic groups.

Administration, Oral↗

Nuclear morphometric changes and therapy monitoring in patients with endometrial hyperplasia: a study comparing effects of intrauterine levonorgestrel and systemic medroxyprogesterone.

OBJECTIVE: To show that local application of the levonorgestrel intrauterine device was a better therapy for endometrial hyperplasia (EH) compared to per-oral gestagen treatment based on subjective (WHO criteria) and objective (prognostic data-based morphometric and stereological method/D score, predicting the risk of cancer development for each single patient) evaluation. METHODS: Women between 30 and 70 years with EH and D score > 0 were treated with levonorgestrel intrauterine device (n = 26) and the results compared to a historic group of women treated with per-oral gestagen (n = 31). In both treatment groups only patients with low risk (D score > 1) and uncertain risk (D score = 0-1) of cancer development were included. Endometrial specimens were investigated prior to treatment and after 3 months of therapy. The endometrial samples from the two groups were examined by light microscopy and objective data-based morphometry to assess tissue characteristics and to evaluate nuclear size variation. RESULTS: After 3 months all patients treated with levonorgestrel intrauterine device showed regression of hyperplasia, whereas 14 of 31 patients in the per-oral group still had persisting disease. The objective morphometric analysis showed reduction in nuclear size for both treatment groups, including the D score > 1 as well as the D score 0-1 patients. However, the reduction was most obvious for the levonorgestrel intrauterine device-treated patients with initial D score of 0-1. CONCLUSION: The present study indicates that levonorgestrel intrauterine device is a superior alternative to per oral treatment of endometrial hyperplasia. By using objective morphometric treatment monitoring we have shown that the hyperplasia patients with the highest malignant potential (D score = 0-1) were those taking most benefit from local high-dose levonorgestrel therapy.

Adult↗

Post-abortion depot medroxyprogesterone acetate continuation rates: a randomized trial of cyclic estradiol.

Irregular menstrual bleeding is a common reason for discontinuation of depot medroyprogesterone acetate (DMPA) contraception. We conducted a double-blind, randomized placebo controlled trial to estimate if transdermal estradiol used in a cyclic fashion could make DMPA bleeding patterns more acceptable and improve DMPA continuation rates. Women initiating DMPA contraception immediately post-abortion (N = 132) were randomized to receive either a low sustained dose of transdermal 17-beta estradiol (0.10 mg/day, Climara) or an identical placebo to be used in a cyclic manner for 3 months. Bleeding patterns, contraceptive use, and pregnancy rates were measured for 1 year after enrollment. Cyclic transdermal estrogen did not create regular bleeding patterns in new users of DMPA and had no effect on DMPA continuation rates (relative hazard = 0.93, 95%CI 0.65-1.33). By 12 months after enrollment, 19.4% of those randomized to estrogen and 23.9% of those randomized to placebo were still using DMPA for contraception. There was no difference in the frequency of DMPA discontinuation primarily for abnormal uterine bleeding between groups (relative risk ratio = 0.95, 95%CI 0.40-2.23). Few women who discontinued DMPA switched to highly effective methods of contraception and within 1 year of an abortion, there were 18 repeat pregnancies (21.9%). Compliance with the estrogen patches was poor resulting in early study termination and inadequate statistical power to detect a clinically significant difference in DMPA continuation rates. Continuation rates of DMPA were low and repeat pregnancy rates were high among women initiating DMPA at the time of abortion. Cyclic transdermal estradiol use is an unacceptable regimen for preventing the irregular bleeding associated with DMPA initiation.

Abortion, Induced↗