Uterine bleeding with hormone therapies in menopausal women: a systematic review

Abstract

Uterine bleeding is a common reason why women discontinue menopausal hormone therapy (HT). This systematic review compared bleeding profiles reported in studies for continuous-combined HT approved in North America and Europe for moderate to severe vasomotor symptoms in postmenopausal women with a uterus. Non-head-to-head studies showed that uterine bleeding varies by formulation and administration route, with oral having a better bleeding profile than transdermal formulations. Cumulative amenorrhea over a year ranged from 18 to 61% with oral HT and from 9 to 27% with transdermal HT, as reported for continuous-combined HT containing 17b-estradiol (E2)/progesterone (P4) (56%), E2/norethisterone acetate (NETA) (49%), E2/drospirenone (45%), conjugated equine estrogens/medroxyprogesterone acetate (18-54%), ethinyl estradiol/NETA (31-61%), E2/levonorgestrel patch (16%), and E2/NETA patch (9-27%). Amenorrhea rates and the mean number of bleeding/spotting days improved over time. The oral E2/P4 combination was amongst those with lower bleeding rates and may be an appropriate alternative for millions of women seeking bioidentical HT and/or those who have bleeding concerns with other HT.

Unexpected vaginal bleeding and COVID-19 vaccination in nonmenstruating women

“…After the menopause, the endometrium normally undergoes a gradual atrophy, starting with an inactive phase in which neither proliferation nor secretion is present and ending in a thin layer, often with cystic cavities (30). HRT, most commonly a combination of estrogen and progestogen, may interfere with the physiological atrophy (30,31), and vaginal bleeding is a common side effect (32). Ljung et al (12) observed a slightly stronger association between vaccination and PMB after the third dose in a subsample analysis of nonhormone users as compared to the analysis on the complete sample.…”

“…After the menopause, the endometrium normally undergoes a gradual atrophy, starting with an inactive phase in which neither proliferation nor secretion is present and ending in a thin layer, often with cystic cavities ( 30 ). HRT, most commonly a combination of estrogen and progestogen, may interfere with the physiological atrophy ( 30 , 31 ), and vaginal bleeding is a common side effect ( 32 ). Ljung et al.…”

Management of unscheduled bleeding on HRT: A joint guideline on behalf of the British Menopause Society, Royal College Obstetricians and Gynaecologists, British Gynaecological Cancer Society, British Society for Gynaecological Endoscopy, Faculty of Sexual and Reproductive Health, Royal College of General Practitioners and Getting it Right First Time

“…Cumulative amenorrhoea over 12 months was lower in the transdermal preparations (9-27%), when compared to oral preparations (18-61%), irrespective of the constituents. 93 As perimenopausal women have higher rates of unscheduled bleeding and proliferation on biopsy, than postmenopausal women, 94,95 an oral preparation (if no risk factors for thrombosis), could be offered as either, a first-line therapy or, to women whose initial preference was for transdermal but have unscheduled bleeding episodes despite adjustments.…”

British Menopause Society tools for clinicians: Progestogens and endometrial protection

“…Consideration should also be given to assessment of the endometrial cavity by hysteroscopy where clinically indicated or in cases with persistent bleeding and an endometrial biopsy obtained to assess for and exclude endometrial pathology. 2,[30][31][32] The risk of endometrial cancer in women with unscheduled bleeding on HRT is significantly lower than that with postmenopausal bleeding in women not on HRT especially in women who had not been experiencing bleeding before commencing HRT. 4 For the majority of women with unscheduled bleeding on HRT, modifying progestogen intake often controls the bleeding especially in women who experience unscheduled bleeding in the first few months after commencing HRT.…”

“…Consideration should also be given to assessment of the endometrial cavity by hysteroscopy where clinically indicated or in cases with persistent bleeding and an endometrial biopsy obtained to assess for and exclude endometrial pathology. 2,30–32…”