What is the cause of continuous bleeding for four months in a patient with an endometrial thickness of 0.6 cm, who was taking progesterone and estrogen (hormone replacement therapy) transdermally, and experienced cessation of bleeding after discontinuing progesterone and restarting estrogen, with subsequent cyclical progesterone therapy and no bleeding?

From the Guidelines

I strongly recommend continuing the cyclical progesterone therapy that has successfully stopped your bleeding, while monitoring your endometrial thickness, as this approach has been shown to effectively regulate endometrial shedding patterns and prevent unpredictable continuous bleeding 1. Your uterine lining measurement of 0.6 cm (6 mm) is within normal range. The continuous bleeding you experienced for four months while on combined estrogen and progesterone therapy (continuous regimen) was likely due to hormonal imbalance. Switching to cyclical progesterone has allowed for controlled withdrawal bleeding rather than unpredictable continuous bleeding.

Key Considerations

• The cyclical approach works because it mimics the natural menstrual cycle, allowing for organized shedding of the endometrium rather than the continuous breakdown that was causing your prolonged bleeding.
• For optimal results, take progesterone (typically 200mg daily) for 12-14 days each month, followed by a hormone-free interval, as suggested by the most recent guidelines 1.
• Regular follow-up appointments every 3-6 months are important to reassess endometrial thickness and bleeding patterns.
• If bleeding resumes or becomes irregular, your hormone regimen may need adjustment, and alternative progestins such as natural micronized progesterone or dydrogesterone could be considered 1.

Hormone Regimen

• The choice of progestin is crucial, and natural micronized progesterone has been shown to have a favorable profile in terms of minimizing hormonal-related cardiovascular risks and thrombotic risk 1.
• The dose of progestogen should be based on the concurrent dose of estrogen administered, and the cyclic administration allows for earlier recognition of a pregnancy, although this may be less relevant in your case.

Monitoring and Follow-up

• Regular monitoring of your endometrial thickness and bleeding patterns is essential to ensure the effectiveness of the cyclical progesterone therapy and to make any necessary adjustments to your hormone regimen 1.
• The American College of Obstetricians and Gynecologists (ACOG) guidelines suggest that medical treatments for abnormal uterine bleeding associated with ovulatory dysfunction include progestin-only contraception and combined hormonal contraception, and that surgery may be an option if medical treatment fails or is contraindicated 1.

From the FDA Drug Label

In cases of breakthrough bleeding, as in all cases of irregular bleeding per vaginum, nonfunctional causes should be borne in mind and adequate diagnostic measures undertaken. Whether this will provide protection from endometrial carcinoma has not been clearly established A decrease in glucose tolerance has been observed in a small percentage of patients on estrogen-progestin combination treatment The patient's continuous bleeding for four months while on progesterone and estrogen suggests that the hormone regimen may not be effectively managing the bleeding.

• The fact that bleeding stopped after stopping progesterone and estrogen and restarted 15 days after cyclical progesterone with no bleeding indicates that the hormone regimen may be a contributing factor to the bleeding.
• However, the FDA drug label does not provide a clear explanation for the patient's bleeding or the effectiveness of the hormone regimen in preventing endometrial hyperplasia or carcinoma.
• Given the unclear evidence, a conservative clinical decision would be to closely monitor the patient's bleeding and adjust the hormone regimen as needed to minimize the risk of adverse effects, including endometrial hyperplasia or carcinoma 2.

From the Research

Uterine Lining Measurement and Bleeding

• The uterine lining is measured at 0.6 cm, which is a relatively thin lining.
• The patient is on progesterone and estrogen transdermal therapy, which can affect uterine lining thickness and bleeding patterns 3.
• Continuous bleeding for four months suggests an abnormal uterine bleeding pattern, which can be caused by various factors, including hormone therapy 4.

Effect of Stopping Progesterone and Estrogen

• Stopping progesterone and estrogen therapy led to cessation of bleeding, suggesting that the hormone therapy may have been contributing to the abnormal bleeding pattern.
• Restarting estrogen 15 days after cyclical progesterone with no bleeding suggests that the patient's uterine lining is responsive to hormone therapy and can regulate bleeding patterns 3.

Comparison of Hormone Therapies

• Studies have shown that different hormone therapies can have varying effects on uterine bleeding patterns, with oral formulations tend to have a better bleeding profile than transdermal formulations 3.
• The use of medroxyprogesterone acetate (MPA) has been shown to be effective in treating endometrial hyperplasia, with cyclic MPA regimen being more acceptable to patients than continuous MPA regimen 5.
• A systematic review and network meta-analysis found that MPA is the most effective single agent for endometrial hyperplasia, while the combination of metformin can achieve a more significant effect 6.