Bleeding On Hormone Replacement Therapy (HRT)

Bleeding on Hormone Replacement Therapy (HRT)

In women with a natural menstrual cycle, bleeding typically follows a predictable pattern based on the hormonal phases:

• Follicular Phase (Proliferative Phase): The first two weeks of the cycle, during which oestrogen stimulates the growth of the uterine lining.
• Luteal Phase (Secretory Phase): The second two weeks, where progesterone down-regulates oestrogen receptors, halts further growth of the endometrium, and makes the lining more glandular in preparation for possible implantation and pregnancy.

When levels of oestrogen and progesterone drop before menstruation, the uterine lining becomes unstable and is shed—this results in a menstrual bleed.

Why Does Unpredictable Bleeding Occur On HRT?

In postmenopausal women with a uterus it is possible to get unpredictable bleeding.

• Administering oestrogen stimulates endometrial growth. Eventually, this may lead to instability and shedding of the uterine lining, resulting in unpredictable bleeding. In order to avoid bleeding, it’s necessary to use lower doses of oestrogen and give it alongside a continuous daily dose of progesterone. Progesterone suppresses oestrogen receptors and limits the proliferative effect of oestrogen on the uterine lining, therefore, it can result in no bleeding. A common approach is to use 100mg of oral progesterone daily.
• However, whilst this can be effective in alleviating hot flushes and other menopausal symptoms, over time, progesterone receptor responsiveness may decline, leading to breakthrough bleeding.
• The dose of oestrogen through transdermal delivery can also be slightly unstable. Estrogen patches can release more oestradiol on the first day than on subsequent days. Likewise, oestrogen gel can absorb differently depending on skin type or skin temperature. These fluctuations can lead to hormonal fluctuations and potential endometrial instability; similar to natural hormone withdrawal and can result in uterine bleeding.

How To Avoid Unpredictable Bleeding On HRT

• If this is occurring frequently, it may be advisable to change to a cyclical regimen. This would involve daily transdermal oestrogen and 14 days of progesterone each month, with a 14 day break of progesterone. This is similar to the pattern we would see in our pre-menopausal hormones. This would lead to a predictable bleed when progesterone stops each month.
• However, even with cyclical regimens, unscheduled bleeding can occur. It’s important to understand that HRT doesn’t perfectly replicate the natural menstrual cycle—it only mimics it to some extent.

When to Investigate Further

• Most bleeding on HRT is benign but can be bothersome.
• If irregular bleeding continues despite adjusting the HRT regimen, further investigation is necessary.
  • Pelvic Ultrasound: To assess for endometrial thickness, polyps, or fibroids.
  • Hysteroscopy and/or D&C: May be required for endometrial biopsy to rule out more sinister pathology, such as endometrial cancer.

Reframing Bleeding

Instead of viewing bleeding as purely negative, it can be seen as an indication that oestrogen is biologically active and affecting the endometrium—essentially, a sign that the therapy is having an effect.