What are the risks of progesterone therapy in patients who have undergone a hysterectomy for its effects on mood, sleep, or other symptoms?

From the Guidelines

Progesterone therapy after hysterectomy is not recommended for the primary prevention of chronic conditions due to its associated risks, including an increased risk for stroke, dementia, gallbladder disease, and urinary incontinence, as well as a small increase in the incidence of invasive breast cancer and breast cancer deaths. The main concerns with progesterone therapy include potential blood clots (venous thromboembolism), stroke, breast cancer (with long-term use), fluid retention, headaches, breast tenderness, and mood changes 1. The risk profile depends on several factors including age, medical history, whether the ovaries were removed during hysterectomy, and the specific type of progesterone used. Bioidentical progesterone typically has fewer side effects than synthetic progestins. If considering progesterone therapy, it is essential to start with the lowest effective dose and regularly reassess treatment. The benefits for mood and sleep occur because progesterone affects GABA receptors in the brain, producing calming effects. However, the USPSTF recommends against the use of estrogen and progestin for the prevention of chronic conditions in postmenopausal women, including those who have had a hysterectomy 1.

Some key points to consider when evaluating the risks and benefits of progesterone therapy after hysterectomy include:

• The type and dose of progesterone used, with bioidentical progesterone typically having fewer side effects than synthetic progestins
• The individual's age, medical history, and whether the ovaries were removed during hysterectomy
• The potential benefits of progesterone therapy for mood, sleep, and other symptoms
• The importance of regular reassessment and individualization of treatment
• The need to discuss specific health history with a healthcare provider before starting progesterone, especially if there is a history of breast cancer, blood clots, liver disease, or unexplained vaginal bleeding.

It is crucial to weigh the potential benefits of progesterone therapy against its associated risks and to consider alternative treatment options for managing symptoms after hysterectomy.

From the FDA Drug Label

Serious, but less common side effects include: Risk to the Fetus: Cases of cleft palate, cleft lip, hypospadias, ventricular septal defect, patent ductus arteriosus, and other congenital heart defects. Abnormal Blood Clotting: Stroke, heart attack, pulmonary embolus, visual loss or blindness Some of the warning signs of serious side effects include: Changes in vision or speech Sudden new severe headaches Severe pains in your chest or legs with or without shortness of breath, weakness and fatigue Dizziness and faintness Vomiting Less serious, but common side effects include: Headaches Breast pain Irregular vaginal bleeding or spotting Stomach or abdominal cramps, bloating Nausea and vomiting Hair loss Fluid retention Vaginal yeast infection Progesterone may cause some degree of fluid retention Women with conditions that might be influenced by this factor, such as cardiac or renal dysfunction, warrant careful observation. Progesterone capsules may cause transient dizziness and drowsiness and should be used with caution when driving a motor vehicle or operating machinery.

The risks associated with progesterone use include:

• Serious side effects: abnormal blood clotting, stroke, heart attack, pulmonary embolus, visual loss or blindness
• Common side effects: headaches, breast pain, irregular vaginal bleeding or spotting, stomach or abdominal cramps, bloating, nausea and vomiting, hair loss, fluid retention, vaginal yeast infection
• Special precautions: women with cardiac or renal dysfunction should be carefully observed due to the potential for fluid retention, and caution should be used when driving or operating machinery due to potential dizziness and drowsiness 2 2

From the Research

Risks Associated with Progesterone Therapy

• The use of progesterone in women who have undergone hysterectomy may still be beneficial for its effects on mood, sleep, or other symptoms, but it is essential to consider the potential risks [(3,4,5)].
• Studies have shown that progestogens, including micronized progesterone, may increase the risk of invasive breast cancer, although the risk may vary depending on the type of progestogen used [(4,6)].
• Micronized progesterone may be a safer option compared to synthetic progestogens, with a more acceptable metabolic profile and potentially lower risk of breast cancer [(4,7,6)].
• The decision to use progesterone therapy in women who have undergone hysterectomy should involve an individualized risk/benefit analysis, taking into account the potential benefits and risks, including the risk of breast cancer [(5,6)].
• Women should be counseled on the potential risks and benefits of combined hormone therapy, including the risk of breast cancer, and should be informed about other modifiable and non-modifiable breast cancer risk factors 6.