Will postmenopausal women experience monthly bleeding with a regimen of 2 weeks of progesterone and estrogen (Hormone Replacement Therapy (HRT)) via a transdermal patch?

From the Guidelines

Post-menopausal women on hormone replacement therapy (HRT) using a cyclic regimen with an estrogen patch continuously and progesterone for 2 weeks per month will typically experience monthly withdrawal bleeding. This bleeding occurs when the progesterone is stopped at the end of the 2-week period, similar to a menstrual period. The bleeding pattern varies among women but generally starts within a few days after stopping progesterone and lasts 3-7 days. Common regimens include continuous estrogen (such as estradiol patches 0.025-0.1 mg/day) with oral micronized progesterone (100-200 mg daily) or medroxyprogesterone acetate (5-10 mg daily) for the first 12-14 days of each month 1. If monthly bleeding is undesirable, a continuous combined regimen (taking both hormones daily without breaks) may be preferable, which typically leads to no bleeding after an initial adjustment period of 3-6 months. Women should be informed about this expected bleeding pattern before starting therapy to avoid unnecessary concern, and any unexpected or heavy bleeding should be evaluated by a healthcare provider to rule out endometrial pathology. Key considerations for HRT include the type, dose, duration of use, route of administration, timing of initiation, and whether a progesterone is used, as these factors influence the risks and benefits of therapy 1. In general, the lowest effective dose of systemic HRT consistent with treatment goals should be the therapeutic goal, and locally applied vaginal estrogen is generally thought to be safe due to minimal systemic absorption 1. Transdermal systemic agents may be preferred for patients with cardiovascular disease to minimize activation of thrombotic factors and effects on lipids 1. Ultimately, the decision to use HRT and the choice of regimen should be individualized based on patient preferences, known and perceived risks and benefits, and symptom severity, with periodic review of the indications, benefits, and risks of continuing or discontinuing use of HRT 1.

From the Research

Hormone Replacement Therapy (HRT) in Postmenopausal Women

• HRT is an effective treatment for symptoms related to menopause, but it can increase the risk of endometrial hyperplasia and carcinoma if not properly managed 2, 3.
• The addition of progestogen to estrogen therapy can reduce the risk of endometrial hyperplasia, but it may also cause irregular bleeding and spotting 2, 3.
• The frequency and duration of progestogen administration can affect the risk of endometrial hyperplasia and irregular bleeding, with sequential regimens (progestogen given for 10-14 days per month) being more effective in preventing endometrial hyperplasia than continuous combined regimens 3, 4.

Bleeding Patterns with HRT

• Women on HRT with a sequential regimen (2 weeks of progesterone and estrogen patch) may experience withdrawal bleeding, which can be similar to a monthly menstrual period 4.
• The frequency and intensity of bleeding can vary depending on the individual, the dose and type of estrogen and progestogen, and the duration of treatment 3, 5.
• Some studies suggest that continuous combined regimens may be associated with less bleeding than sequential regimens, but this can depend on the specific formulation and dose of the hormones 3, 5.

Estrogen and Progesterone Formulations

• Different formulations of estrogen (e.g. transdermal estradiol, conjugated equine estrogens) and progestogen (e.g. micronized progesterone, medroxyprogesterone acetate) can have varying effects on the risk of endometrial hyperplasia and irregular bleeding 2, 6, 4.
• The choice of formulation and dose can depend on individual factors, such as the presence of a uterus, the severity of symptoms, and the risk of adverse effects 6, 4.