Absorption and metabolism of oral progesterone when administered twice daily
Padwick ML , Endacott J , Matson C
Whitehead MI
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Abstract
The absorption, metabolism, and clearance of progesterone (P) from the peripheral circulation were investigated in five postmenopausal women after oral administration of 100 mg at 9:00 A.M. and 200 mg at 9:00 P.M. for 5 consecutive days. Mean peak plasma concentrations of P were observed 2 hours after ingestion of both the 100 and 200 mg doses and were 22.7 and 47.7 nmol/l, respectively. Of the three metabolites studied, the plasma concentrations of pregnanediol-3 alpha-glucuronide were most raised by treatment; those of 17-hydroxyprogesterone were least raised. Increases in the plasma levels of 20 alpha-dihydroprogesterone were more sustained than those of P, and the plasma concentrations remained elevated at approximately 20 nmol/l for at least 12 hours after P administration. We conclude that administration of oral P 100 mg in the morning and 200 mg at night increases the circulating concentrations of P and the biologically active metabolite 20 alpha-dihydroprogesterone, and that the duration of these increases is sufficient to evoke progestational responses in responsive end-organs.
Padwick, M. L., Endacott, J., Matson, C., & Whitehead, M. I. (1986). Absorption and metabolism of oral progesterone when administered twice daily. Fertility and sterility, 46(3), 402-407.
Padwick ML, Endacott J, Matson C, Whitehead MI. Absorption and metabolism of oral progesterone when administered twice daily. Fertil Steril. 1986;46(3):402-407.
Padwick, M. L., et al. "Absorption and metabolism of oral progesterone when administered twice daily." Fertility and sterility, vol. 46, no. 3, 1986, pp. 402-407.
Keywords
17-alpha-Hydroxyprogesterone, 20-alpha-Dihydroprogesterone/metabolism, Absorption, Drug Administration Schedule, Female, Humans, Hydroxyprogesterones/metabolism, Middle Aged, Organization and Administration, Pregnanediol/analogs & Derivatives/metabolism, Progesterone/administration & Dosage/metabolism, Time Factors, Hydroxyprogesterones, 20-alpha-Dihydroprogesterone, Pregnanediol-3 Alpha-glucuronide, Progesterone, 17-alpha-Hydroxyprogesterone, Pregnanediol
The oral route of progesterone administration has long been considered impractical because of poor absorption and short biologic half-life. Recent reports suggest that micronization of progesterone enhances absorption and increases serum and tissue levels of progesterone. This study checks serum progesterone levels before and 0.5, 1, 2, 3, 4, and 6 hours after oral administration of 200 mg of progesterone in seven subjects. Progesterone was plain milled, micronized, plain milled in oil, micronized in oil, or micronized in enteric-coated capsules. All patients exhibited a significant increase in serum progesterone levels after oral progesterone administration. Mean peak progesterone levels (30.3 +/- 7.0 ng/ml) (p less than 0.005) were achieved with micronized progesterone in oil at 2.0 +/- 0.3 (p less than 0.05) hours after administration. Four types of oral progesterone had equivalent mean peak elevations plain milled, 9.6 +/- 2.5 ng/ml at 4.0 +/- 0.5 hours; micronized 13.2 +/- 2.4 ng/ml at 3.2 +/- 0.4 hours; plain milled in oil, 11.3 +/- 3.0 ng/ml at 4.0 +/- 0.5 hours; and micronized in enteric-coated capsules, 11.2 +/- 3.0 ng/ml at 4.1 +/- 0.7 hours. Contrary to traditional teaching, these data show that significant serum progesterone levels can be achieved by oral administration. Absorption can be significantly improved by the physical characteristics of the progesterone and the vehicle used with oral administration.
Practice Committee of the American Society for Reproductive Medicine, 2026·Fertility and Sterility
Current strategies for the assessment and treatment of recurrent pregnancy loss are discussed. This replaces the previous document, titled, "Evaluation and treatment a committee opinion," last published in 2012.
This narrative review examines the evidence for medical optimization of inflammatory conditions, vitamin deficiencies, endocrine disorders, immune dysregulation, oligo-ovulation, and luteal phase factors to improve fertility outcomes in women attempting to conceive through natural or timed intercourse. Overall, there is a paucity of data with respect to these categories among patients pursuing timed intercourse, precluding our ability to draw strong recommendations. However, there is strong evidence supporting treatment of endocrine disorders, specifically overt thyroid dysfunction and hyperprolactinemia, as well as oligo-ovulation. Conversely, treatment of subclinical hypothyroidism is not recommended. The current data are insufficient to support empiric use of antiinflammatory medications, corticosteroids, thyroid hormones, or vitamins or supplements to improve chances of pregnancy in a general infertility population.
Restorative Reproductive Medicine (RRM) aims to restore fertility by diagnosing and treating the underlying causes of infertility. RRM is frequently promoted as an alternative to assisted reproductive technology (ART), despite uncertainty regarding its comparative effectiveness and safety. Where delayed childbearing and infertility are becoming more common, reliance on optimization of natural physiology alone may delay effective treatment and compromise reproductive outcomes. A systematic review of the current evidence comparing RRM to either ART or unassisted conception is, therefore, essential to inform clinical practice, guideline development, and shared decision-making for patients experiencing infertility. To assess the effectiveness and safety of RRM approaches, evaluated as a whole, rather than as individual components, compared with ART and medically unassisted conception in couples experiencing infertility. A systematic literature search of MEDLINE, Embase, CENTRAL and the Journal of Restorative Reproductive Medicine from inception to 28 November 2025. We included randomized control trials (RCTs) or nonrandomized comparative studies evaluating reproductive and safety outcomes of RRM as a unified treatment, compared with either ART or expectant management (attempted medically unassisted conception). Two reviewers independently screened titles, abstracts and full texts with disagreements resolved by a third reviewer. We retrieved 724 records, of which 16 studies underwent full-text review. No RCTs or comparative observational studies were identified. All 16 full-text studies were excluded for an ineligible study design (no control group); most were cohort studies in which all participants underwent RRM. Ten studies reported reproductive outcomes; nine of these made claims regarding the benefits or effectiveness of RRM. None of these claims were supported by the study designs used, as the lack of a comparison group precludes reliable estimation of treatment effects. Consequently, these studies cannot provide valid estimates of RRM success rates, nor permit any meaningful inference about its effectiveness relative to unassisted conception or ART. Large-scale RCTs or prospective cohort studies reporting effectiveness and safety outcomes are required to inform evidence-based fertility guidelines. There are no comparative studies to support reliable estimates of the safety and effectiveness of RRM compared with ART or medically unassisted conception for couples experiencing infertility.