What are the side effects of micronized progesterone?

From the Guidelines

Micronized progesterone is generally well-tolerated, but it can cause several side effects, including drowsiness, sedation, fatigue, dizziness, headaches, breast tenderness, bloating, nausea, and mood changes, with the most recent evidence suggesting a favorable safety profile compared to synthetic progestogens 1. When taken orally, micronized progesterone passes through the liver, which can cause drowsiness due to its metabolites having sedative effects on the brain, and for this reason, it's often recommended to take oral progesterone at bedtime. Some women report vaginal discharge, irritation, or itching when using vaginal formulations. Less common but more serious side effects include depression, blood clots, allergic reactions, and changes in blood pressure. The risk of side effects typically depends on the dose, route of administration, and individual sensitivity, with oral forms generally causing more systemic side effects than vaginal or topical applications because they undergo first-pass metabolism in the liver. Some key considerations include:

• Individuals with severe peanut allergies should not receive micronized progesterone capsules due to the presence of peanut oil in the excipients 1
• Vaginal gel formulations do not contain peanut oil and can be used in patients with peanut allergies
• Contraindications to vaginal progesterone treatment include typical contraindications to progesterone hormonal therapy, such as hormone receptor-positive breast cancer
• Vaginal progesterone has not been associated with an increased risk of gestational diabetes mellitus or glucose intolerance 1 Most side effects are mild and temporary, often improving after the first few weeks of treatment as the body adjusts to the hormone. If side effects are severe or persistent, patients should consult their healthcare provider, as dosage adjustments or alternative formulations may be needed.

From the FDA Drug Label

Side effects are grouped by how serious they are and how often they happen when you are treated: 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

The possible side effects of micronized progesterone include:

• Serious side effects: Risk to the fetus, 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 These side effects are based on information from 2, 2, and 2.

From the Research

Side Effects of Micronized Progesterone

• The most common side effects associated with micronized progesterone include drowsiness and dizziness 3.
• Micronized progesterone has been shown to have a better safety profile compared to synthetic progestins, with a lower risk of metabolic ailments, breast cancer, and veno-thromboembolism 3, 4.
• Unlike synthetic progestins, micronized progesterone does not increase cell proliferation in breast tissue in postmenopausal women 5.
• Micronized progesterone has been found to alleviate symptoms of anxiety and depression, as well as sleep problems, and improve working memory in peri- and menopausal women 3, 6.
• The use of micronized progesterone in combination with estrogens has been associated with a small increase in the risk of invasive breast cancer, although this risk is believed to be lower compared to synthetic progestins 5, 4.

Comparison with Synthetic Progestins

• Micronized progesterone has been shown to have a more favorable profile compared to synthetic progestins, such as medroxyprogesterone acetate (MPA) 5, 3.
• The non-specific effects of MPA, including glucocorticoid activity and differences in the regulation of gene expression, may contribute to its increased risk of side effects compared to micronized progesterone 5.

Therapeutic Uses

• Micronized progesterone is used for various therapeutic indications, including secondary amenorrhea, premenopausal bleeding disorders, luteal phase deficiency, premenstrual syndrome, polycystic ovary syndrome, and menopause symptoms 3, 7, 6.
• Micronized progesterone has been found to be effective in treating hot flushes and night sweats, improving sleep, and preventing breast cancer in estrogen-treated women 6.