Is Prometrium a Progestin?
No, Prometrium (micronized progesterone) is NOT a progestin—it is bioidentical progesterone, chemically identical to the hormone produced by the human ovary, whereas progestins are synthetic analogs with different molecular structures and biological effects. 1
Key Distinction Between Progesterone and Progestins
Prometrium contains natural progesterone that is micronized for improved oral bioavailability. The FDA label explicitly states that progesterone in Prometrium "is synthesized from a starting material from a plant source and is chemically identical to progesterone of human ovarian origin." 1 This is fundamentally different from synthetic progestins like medroxyprogesterone acetate (MPA), norethisterone, or levonorgestrel, which are structurally modified compounds. 2
Clinical Implications of This Distinction
The difference between natural progesterone and synthetic progestins has significant clinical consequences:
Cardiovascular and Metabolic Profile
- Micronized progesterone demonstrates superior cardiovascular safety compared to synthetic progestins. Studies show it minimizes hormonal-related cardiovascular risks, has neutral or beneficial effects on blood pressure, and exhibits one of the best safety profiles regarding thrombotic risk. 2, 3
- Synthetic progestins like MPA negatively impact lipid profiles, vasomotion, and carbohydrate metabolism more than micronized progesterone. 2
Breast Tissue Effects
- Micronized progesterone does not increase cell proliferation in breast tissue in postmenopausal women, unlike synthetic MPA. 4
- The opposing effects are related to non-specific activities of synthetic progestins, including glucocorticoid activity and differences in gene expression regulation. 4
Receptor Binding Characteristics
- Natural progesterone binds specifically to progesterone receptors and also exhibits anti-estrogenic, anti-androgenic, and anti-mineralocorticoid effects through interference with other steroid binding sites. 5
- Synthetic progestins have variable receptor affinities and may exhibit androgenic or other non-progesterone-like effects depending on their structure. 6
Guideline Recommendations
The European Society for Human Reproduction and Embryology (ESHRE) includes micronized progesterone among recommended progestogens for hormone replacement therapy in women with ovarian insufficiency, specifically citing its safer pharmacological profile. 2, 3 This recommendation distinguishes it from synthetic progestins while acknowledging its role as a progestogen (progesterone-like agent) in clinical practice.
Common Clinical Pitfall
The term "progestogen" is often used as an umbrella term that encompasses both natural progesterone and synthetic progestins, which can create confusion. 2 When prescribing or discussing hormone therapy, it is critical to specify whether you are using bioidentical progesterone (like Prometrium) or a synthetic progestin, as they are not interchangeable and have distinct safety profiles.
Formulation Details
Prometrium capsules contain peanut oil as an excipient, making them contraindicated in patients with severe peanut allergies. 7, 1 The micronization process increases oral bioavailability, with maximum serum concentrations attained within 1.5-3 hours after administration. 1