Can Hormone Replacement Therapy (HRT) cause bleeding as a side effect?

Yes, Hormone Replacement Therapy (HRT) Commonly Causes Bleeding as a Side Effect

Breakthrough bleeding and unscheduled vaginal bleeding are well-established and common side effects of HRT, occurring in a substantial proportion of users, particularly during the initial months of therapy. 1, 2

Incidence and Patterns of Bleeding

• Approximately 38-42% of women starting HRT experience at least one episode of unexpected vaginal bleeding requiring clinical evaluation, regardless of whether they use cyclic or continuous combined regimens 3
• Bleeding is particularly common during the first 3-6 months of HRT use, with rates decreasing over time in continuous combined regimens 4, 3
• Among women continuing HRT beyond 2 years, continuous combined regimens show lower bleeding rates (22.3 events per 100 patient-years) compared to cyclic regimens (37.8 events per 100 patient-years) 3

Mechanisms and Contributing Factors

• The bleeding disturbances result from predominantly progestogenic effects on the endometrial vasculature, similar to changes seen with long-term low-dose progestogen-only contraceptives 1
• Estrogen dose directly correlates with bleeding incidence - higher doses cause more frequent bleeding episodes 2
• The mechanisms underlying unscheduled bleeding remain poorly understood, but involve complex vascular and endometrial changes 1

Clinical Management Approach

Initial Counseling

• Inform patients before starting HRT that bleeding irregularities are expected, generally not harmful, and usually improve with continued use 4
• This enhanced counseling reduces discontinuation rates 4

Dose Optimization

• Consider low-dose formulations (0.3 mg conjugated estrogens, 0.5 mg oral estradiol, or 25 μg transdermal estradiol) to minimize bleeding while maintaining efficacy for vasomotor symptoms and bone protection 5, 2
• Low-dose regimens achieve amenorrhea in the majority of women after several months with fewer side effects 5

Regimen Selection

• Continuous combined regimens are designed specifically to minimize bleeding and achieve amenorrhea, though breakthrough bleeding still occurs initially 6, 5
• After 2 years of use, continuous combined HRT demonstrates superior bleeding profiles compared to cyclic regimens 3

Critical Safety Consideration

Any unexpected postmenopausal bleeding must be appropriately evaluated to exclude endometrial adenocarcinoma, as this remains the primary differential diagnosis 1. Among women with unexpected bleeding on HRT, 12-20% undergo endometrial biopsy for evaluation 3.

Special Population Considerations

Gender-Affirming HRT

• In feminizing hormone therapy, breakthrough bleeding is not typically described as a side effect since these patients do not have functional endometrium unless they are transgender men on testosterone therapy 4
• Testosterone therapy in transgender men causes menstrual suppression, though some may experience pelvic pain and genital dryness 4

Premature Ovarian Insufficiency

• When HRT is used for pubertal induction in adolescents with chemotherapy-induced POI, breakthrough bleeding signals the need to add progestogen for endometrial protection, typically 2-3 years after starting estrogen 4

Autoimmune Disease

• In patients with systemic lupus erythematosus, HRT may cause a modest increase in mild-to-moderate disease flares, though severe exacerbations are not significantly increased 4