Can progesterone be administered to transgender women with an active thromboembolism (blood clot)?

From the Guidelines

Progesterone is generally not recommended for transgender women with active blood clots due to the potential increased risk of thromboembolism. Transgender women with current thrombosis should avoid progesterone, as any hormone that may affect coagulation factors should be used with extreme caution in patients with active clots 1. The priority for a transgender woman with an active blood clot should be treating the clot with appropriate anticoagulation therapy under medical supervision.

Key Considerations

• The risk of venous thromboembolism (VTE) is increased in transgender women undergoing gender-affirming hormone treatment (GAHT) due to the prothrombic effects of estrogen 1.
• Progesterone's thrombotic risk is lower than that of estrogens, but it can still affect coagulation factors and inflammatory markers, potentially worsening an existing thrombotic condition 1.
• The concern for thromboembolism is significant, and any hormone therapy decisions for transgender women with a history of blood clots should involve consultation with both an endocrinologist experienced in transgender care and a hematologist to properly balance gender-affirming care with thrombosis risk management.

Management Approach

• If a transgender woman has an active blood clot, the priority should be treating the clot with appropriate anticoagulation therapy under medical supervision.
• Once the clot has resolved and the patient has completed an appropriate course of anticoagulation, progesterone therapy might be reconsidered after careful risk assessment by a healthcare provider 1.
• It is essential to weigh the benefits of hormone therapy against the potential risks, particularly in patients with a history of thrombotic events, and to consider alternative approaches to gender-affirming care that may minimize these risks.

From the FDA Drug Label

CONTRAINDICATIONS Progesterone capsules should not be used in women with any of the following conditions: ... 4. Active deep vein thrombosis, pulmonary embolism or history of these conditions.

The WHI estrogen plus progestin substudy reported increased risks of deep vein thrombosis, pulmonary embolism, stroke and myocardial infarction in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2. 5 mg], relative to placebo.

Progesterone is contraindicated in patients with active deep vein thrombosis, pulmonary embolism, or a history of these conditions 2. Although the studies mentioned are for estrogen plus progestin therapy, the contraindication for active blood clots is directly stated for progesterone capsules. Therefore, progesterone should not be taken in transgender women who have an active blood clot.

From the Research

Progesterone Use in Transgender Women with Active Blood Clot

• The use of progesterone in transgender women, especially those with an active blood clot, is a complex issue that requires careful consideration of the potential risks and benefits 3, 4, 5.
• Studies have shown that the use of progestogens in gender-affirming hormone therapy (GAHT) for transgender women may increase the risk of thromboembolism, which is a concern for individuals with an active blood clot 3.
• However, other studies have suggested that progesterone itself may not be associated with an increased risk of thrombosis, especially when used in combination with estrogen 5, 6, 7.
• The risk of venous thromboembolism (VTE) is a significant concern for individuals using hormone therapy, and the management of VTE in this population requires careful consideration of the risks and benefits of anticoagulation therapy 4, 5.
• It is essential to weigh the potential benefits of progesterone use in transgender women against the potential risks, particularly in individuals with an active blood clot, and to consider alternative treatment options that may be safer and more effective 3, 4, 5.
• Patient-specific factors, such as the type and dose of hormone therapy, personal and family history of thrombosis, and other prothrombotic risk factors, must be taken into account when making decisions about progesterone use in transgender women with an active blood clot 5.