What Are Micronized Progestins?
Micronized progesterone is natural progesterone that has been processed into tiny particles to enhance its oral bioavailability, making it chemically identical to the progesterone produced by the human ovary but with improved absorption when taken by mouth. 1
Pharmaceutical Characteristics
Micronization is a pharmacotechnical process that reduces natural progesterone into microscopic particles, significantly increasing its bioavailability compared to non-micronized formulations. 2
The oral bioavailability is enhanced through this micronization process, with maximum serum concentrations attained within 1.5-3 hours after oral administration. 1
Micronized progesterone (MP) is chemically identical to endogenous progesterone produced by the corpus luteum, distinguishing it from synthetic progestins which are structurally modified analogs. 1, 3
Clinical Distinction from Synthetic Progestins
Synthetic progestins are testosterone-derived compounds (first through third generation) or spironolactone analogs (fourth generation like drospirenone), whereas micronized progesterone maintains the exact molecular structure of natural progesterone. 4
MP preserves the full biological activity of natural progesterone without many side effects associated with synthetic progestins, particularly regarding cardiovascular and metabolic impacts. 2
Safety Profile Advantages
Micronized progesterone demonstrates superior cardiovascular safety compared to synthetic progestogens, with neutral or beneficial effects on blood pressure and minimal impact on lipid profiles and vasomotion. 4
MP shows one of the best safety profiles for thrombotic risk among all progestogens, though this has not been extensively studied in all populations. 4, 5
The metabolic side effects commonly seen with synthetic progestins (such as medroxyprogesterone acetate's negative effects on carbohydrate metabolism and lipid profiles) are minimized or eliminated with MP. 3
Endometrial Protection
MP effectively transforms estrogen-primed proliferative endometrium into secretory endometrium, providing necessary protection against endometrial hyperplasia and cancer when used with estrogen therapy. 6, 7
For endometrial protection in hormone replacement therapy, MP requires dosing of 200 mg for 12-14 days every 28 days in sequential regimens, or continuous dosing at lower amounts. 4
The protective effect against endometrial hyperplasia does not differ between MP and synthetic progestins, but is affected by regimen and dose, with continuous combined treatment conferring better protection. 7
Guideline-Recommended Uses
The European Society for Human Reproduction and Embryology (ESHRE) includes MP among recommended progestogens in hormone replacement therapy for women with ovarian insufficiency, based on its demonstrated safer pharmacological profile. 4, 5
MP is the first-choice progestogen for women requiring hormone replacement therapy, particularly in those with premature ovarian insufficiency or cancer survivors. 4
Metabolism and Pharmacokinetics
Progesterone is metabolized primarily by the liver to pregnanediols and pregnanolones, which are then conjugated to glucuronide and sulfate metabolites for excretion. 1
The drug is approximately 96-99% protein-bound, primarily to serum albumin (50-54%) and transcortin (43-48%). 1
Concomitant food ingestion increases the bioavailability of oral micronized progesterone capsules relative to fasting state. 1
Side Effect Profile
The primary specific side effect is mild and transient drowsiness, which can be minimized by taking the medication at bedtime. 3, 2
When administered orally, MP acts as a neurosteroid and may provide beneficial effects on brain function, including alleviation of anxiety and depression symptoms, improvement of sleep problems, and enhanced working memory in peri- and menopausal women. 2
Breast Tissue Effects
MP does not increase cell proliferation in breast tissue in postmenopausal women, unlike synthetic medroxyprogesterone acetate (MPA). 7
The opposing effects of MPA versus MP on breast tissue are related to MPA's non-specific effects, including glucocorticoid activity and differences in gene expression regulation. 7
Available Formulations
MP is currently available in injectable, intravaginal, and oral formulations, with the oral micronized preparation having improved bioavailability and fewer reported side effects compared with synthetic progestins. 8
Standard dosing in Europe since 1980 ranges from 100-300 mg daily depending on the regimen (sequential versus continuous) and desired bleeding pattern. 3