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Effects of micronized progesterone added to non-oral estradiol on lipids and cardiovascular risk factors in early postmenopause: a clinical trial

Gislaine Casanova12 and Poli Mara Spritzer123*

Author Affiliations

1 Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, 90035-003, Porto Alegre, Brazil

2 National Institute of Hormones and Women’s Health, CNPq, Rua Ramiro Barcelos, 2350, 90035-003, Porto Alegre, Brazil

3 Laboratory of Molecular Endocrinology, Department of Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2350, 90035-003, Porto Alegre, Brazil

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Lipids in Health and Disease 2012, 11:133  doi:10.1186/1476-511X-11-133

Published: 9 October 2012



Much attention has been drawn to the deleterious effects of adding progestins to estrogen as hormone therapy (HT) in postmenopausal women. Some widely prescribed progestins have been shown to partially oppose the beneficial effects of estrogens on surrogate markers of cardiovascular disease (CVD) risk. Progestins with higher androgenic activity may interfere with lipid profile and glucose tolerance, and could affect mechanisms of estrogen-induced C-reactive protein (CRP) stimulation. Recent data have shown that norpregnane derivatives, but not micronized progesterone, increase the risk of venous thromboembolism among transdermal estrogens users. The aim of the present study was to assess the effects of combining micronized progesterone with non-oral estrogen therapy on lipid profile and cardiovascular risk factors in a sample of early postmenopausal women.


Clinical trial including 40 women receiving intranasal 17β estradiol 3 mg/day for two months and 46 women receiving percutaneous 17β estradiol gel 1.5 mg/day for three months (E2). Both groups received an additional 200 mg/day of micronized progesterone by vaginal route 14 days/month (E2+P). Outcome measures included body weight, waist circumference, body mass index (BMI), lipid profile and ultra-sensitive C-reactive protein (usCRP) at baseline and during the E2 or E2+P portions of treatment.


Mean age was 51±3 years. Mean time since menopause was 22.2±10 months. Most participants were overweight; HT did not change BMI. E2 and E2+P did not affect waist circumference and weight. Menopausal symptoms improved after HT. The effects of intranasal and percutaneous estradiol were similar, regardless of the addition of progesterone. Similarly, for the overall group of 86 women, micronized progesterone did not alter the response to E2. Blood pressure, glucose, insulin, HDL-c, triglycerides, and usCRP remained constant with or without micronized progesterone. Total cholesterol decreased after E2, and progesterone maintained this reduction. LDL-c levels were similar at baseline and with E2, and lower during E2+P in relation to baseline.


Cyclic, short term exposure to vaginal micronized progesterone did not alter the metabolic and cardiovascular effects of non-oral E2 in early, apparently healthy, postmenopausal women.

Trial registration NCT01432028

Lipid profile; Early postmenopause; Micronized progesterone; Non-oral estrogen; Hormone therapy