Oral Micronized Progesterone: Hair and Skin Changes Explained

What does the Prometrium label say about hair and skin?

The label's postmarketing section lists alopecia, pruritus and urticaria under Skin. It says those reports come from a population of uncertain size, so it is not always possible to reliably estimate their frequency or establish a causal relationship to the drug [1].

Acne appears in a different label section. In an open-label postmarketing dosing study, 220 premenopausal women with secondary amenorrhea received conjugated estrogens plus Prometrium 300 mg/day (n=113) or 400 mg/day (n=107) for 10 days of each 28-day cycle; acne was among treatment-emergent reactions reported in 5% or more of subjects [1]. The study had no placebo arm, and all participants received conjugated estrogens [1].

What did controlled studies measure?

The PEPI trial was a 3-year, multicenter, double-blind, placebo-controlled trial in 875 healthy postmenopausal women aged 45 to 64 [3]. It included a conjugated equine estrogen plus cyclic micronized progesterone 200 mg/day for 12 days a month arm [3]. Its primary endpoints were cardiovascular risk factors, and its symptom analysis reported breast discomfort and vasomotor symptoms [3][4].

What is known about skin?

A double-blind, vehicle-controlled study of 40 peri- and postmenopausal women applied 2% progesterone cream for 16 weeks [2]. Objective measurements showed a significant increase in elastic skin properties in the treatment group, with no such effect in the vehicle group [2]. Clinical monitoring found greater increases in skin firmness (23.61% vs 13.24%) and greater reductions in wrinkle counts and depth compared with vehicle [2]. Epidermal hydration and skin surface lipids did not change significantly in either group [2].

The trial used a cream, so its results do not apply to oral capsules.

What is known about hair?

A review of estrogen and skin describes post-menopausal estrogen deficiency as causing atrophic skin changes, with thinner skin, less collagen, decreased elasticity, more wrinkling and dryness, and notes that aging is associated with hair loss [5]. That describes the menopausal hormone environment, not an effect of oral progesterone.

For oral micronized progesterone, the label's alopecia entry gives no rate and no mechanism [1]. Acne and androgenetic alopecia are androgen-mediated skin disorders [6], but that biology does not establish what progesterone does in the scalp.

Does dose or route matter?

The label's approved dose for endometrial protection is 200 mg at bedtime for 12 days sequentially per 28-day cycle, with daily conjugated estrogens, in a postmenopausal woman with a uterus [1]. For secondary amenorrhea, the label dose is 400 mg at bedtime for 10 days [1]. Neither indication is a hair or skin condition, and the only skin trial here used a topical cream rather than these capsules [2].