Incidence of endometrial spotting or bleeding during continuous-combined estrogen-progestin therapy in postmenopausal women with and without hypertension

Menopause. 2015 Oct;22(10):1067-75. doi: 10.1097/GME.0000000000000436.


Objective: Endometrial spotting or bleeding is a common adverse effect among women taking continuous-combined estrogen-progestin therapy. The renin-angiotensin-aldosterone system plays a major role in hypertension and is present in the endometrium. We hypothesized that postmenopausal women with hypertension would have a higher incidence of bleeding compared with postmenopausal women without hypertension.

Methods: A multivariate mixed-effects logistic model estimated the odds ratios for the relationship of hypertension status or use of antihypertensive drugs with endometrial bleeding using the Women's Health Initiative database.

Results: The incidence of spotting or bleeding in the first 12 months of estrogen-progestin use was 42% in women aged 50 to 79 years. Women with hypertension were more likely to experience bleeding than women without hypertension (odds ratio, 1.07; 95% CI, 1.02-1.13). Overall antihypertensive medication use increased bleeding with an odds ratio of 1.24, whereas angiotensin II receptor antagonists had a reduced odds ratio (0.53).

Conclusions: Postmenopausal women with hypertension are more likely to bleed than postmenopausal women without hypertension when taking continuous estrogen-progestin, with less bleeding in women using angiotensin II receptor antagonists. This finding is novel and supports our hypothesis that the endometrial renin-angiotensin-aldosterone system may contribute to endometrial bleeding.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Endometrium / drug effects
  • Estrogen Replacement Therapy / adverse effects*
  • Estrogen Replacement Therapy / methods
  • Estrogens / administration & dosage
  • Estrogens / adverse effects*
  • Female
  • Humans
  • Hypertension / complications*
  • Middle Aged
  • Postmenopause / physiology
  • Progestins / administration & dosage*
  • Progestins / adverse effects
  • Risk Factors
  • Uterine Hemorrhage / chemically induced
  • Uterine Hemorrhage / etiology*
  • Uterine Hemorrhage / prevention & control


  • Estrogens
  • Progestins