Progesterone therapy is safe for the CV system in healthy postmenopausal women

Progesterone therapy, endothelial function and cardiovascular risk factors: a 3-month randomized, placebo-controlled trial in healthy early postmenopausal women

Literature - Prior JC PLoS One. 2014 - PLoS One. 2014 Jan 21;9(1):e84698

Prior JC, Elliott TG, Norman E, et al.
PLoS One. 2014 Jan 21;9(1):e84698.


Cardiovascular system (CVS) risks associated with menopausal ovarian hormone therapy (OHT) have led to many women discontinuing taking OHT [1-3]. Oral micronized progesterone is effective against postmenopausal hot flushes and night sweats [4]. Progestins have shown CVS risks, but there is no class effect of progestogens on the CVS [5]. Oral micronized progesterone appears to have fewer negative effects on HDL-c than other forms of progesterone [6].
Hormones regulating the menstrual cycle are thought to protect women from CV risk [7]. This is mostly attributed to estradiol [8], but progesterone, women’s second ovarian steroid, may also contribute to premenopausal CVS protection.
This study aimed to describe the physiological effects of 12 weeks of oral progesterone therapy on endothelial function and CVS markers to ensure its short-term CV safety as a single therapy in postmenopausal women. In this double-blind trial healthy women who were within 1-11 years of their final menstrual flow, were randomised to active progesterone drug treatment or placebo.

Main results

  • Forearm blood flow showed the expected dose-response to vasodilator concentration in both treatment groups. A non-significantly higher endothelium-dependent response to acetylcholine was seen with progesterone.
  • No differences in changes in weight, body mass index, waist circumference, systolic and diastolic blood pressure or resting heart rate were seen as a result of treatment.
  • Total cholesterol, LDL-c or triglyceride levels were not differently affected by progesterone and placebo. HDL-c levels decreased during progesterone treatment (-0.14 mmol/L, P=0.001). Plasma glucose levels were not affected by progesterone therapy.
  • No meaningful differences in C-reactive protein and albumin were seen between active and placebo therapy, neither in D-dimer.
  • There was no statistically significant difference in Framingham General Cardiovascular Risk Profile scores between the progesterone and placebo arms (0.1, 95%CI: -0.3 to 0.6, P=0.53). Within women changes were also minor and not statistically significant.


Twelve weeks of oral micronized progesterone treatment has a largely neutral effect on CV markers, metabolic, inflammatory and coagulation markers in healthy postmenopausal women. Endothelial function is not compromised, and possibly slightly improved by progesterone. The clinical importance of the small but significant decrease in HDL-c (-7.7%) is currently unclear, since the Framingham CV risk scores were not affected by progesterone therapy.
This randomised trial showed short term safety of oral micronized progesterone for the CVS. 

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1. Grady D, Sawaya GF (2005) Discontinuation of postmenopausal hormone therapy. Am J Med 118 Suppl 12B: 163–165.
2. Menon U, Burnell M, Sharma A, et al. (2007) Decline in use of hormone therapy among postmenopausal women in the United Kingdom. Menopause 14: 462–467.
3. Lawton B, Rose S, McLeod D, Dowell A (2003) Changes in use of hormone replacement therapy after the report from the Women’s Health Initiative: cross sectional survey of users. BMJ 327: 845–846.
4. Hitchcock CL, Prior JC (2012) Oral Micronized Progesterone for Vasomotor Symptoms in Healthy Postmenopausal Women—a placebo-controlled randomized trial. Menopause 19: 886–893.
5. Nath A, Sitruk-Ware R (2009) Different cardiovascular effects of progestins according to structure and activity. Climacteric 12 Suppl 1: 96–101.
6. The Writing Group for the PEPI Trial (1995) Effects of estrogen or estrogen/ progestin regimens on heart disease risk factors in postmenopausal women. The postmenopausal estrogen/progestin interventions (PEPI) trial. JAMA 273: 199–208.
7. Turgeon JL, McDonnell DP, Martin KA, Wise PM (2004) Hormone therapy: physiological complexity belies therapeutic simplicity. Science 304: 1269–1273.
8. Kharazmi E, Dossus L, Rohrmann S, Kaaks R (2010) Pregnancy loss and risk of cardiovascular disease: a prospective population-based cohort study (EPICHeidelberg). Heart doi: 10.1136/hrt.2010.202226: 1–6.

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