Shirin, S., Murray, F., Goshtasebi, A., Kalidasan, D., & Prior, J. C. (2021). Cyclic Progesterone Therapy in Androgenic Polycystic Ovary Syndrome (PCOS)-A 6-Month Pilot Study of a Single Woman's Experience Changes. Medicina (Kaunas, Lithuania), 57(10), 1024. https://doi.org/10.3390/medicina57101024
Shirin S, Murray F, Goshtasebi A, Kalidasan D, Prior JC. Cyclic Progesterone Therapy in Androgenic Polycystic Ovary Syndrome (PCOS)-A 6-Month Pilot Study of a Single Woman's Experience Changes. Medicina (Kaunas). 2021;57(10):1024. doi:10.3390/medicina57101024
Shirin, S., et al. "Cyclic Progesterone Therapy in Androgenic Polycystic Ovary Syndrome (PCOS)-A 6-Month Pilot Study of a Single Woman's Experience Changes." Medicina (Kaunas, Lithuania), vol. 57, no. 10, 2021, pp. 1024.
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RRM Academy Synopsis
One woman with PCOS reported less fluid retention on progesterone
In a six-month pilot, one woman with PCOS (now also called PMOS, polyendocrine metabolic ovarian syndrome) reported regular cycles and less fluid retention on cyclic progesterone. She was 31. She could not take combined hormonal contraceptives. Her diary also showed less breast tenderness and less cervical mucus. Flow and anxiety stayed the same.
Key Findings
Cyclic oral micronized progesterone was associated with shorter, very regular cycles averaging 28.2 days (standard deviation 0.8). Before treatment they were slightly irregular and about 35 days long.
Comparing cycle 1 with cycle 6 across the whole cycle, fluid retention (p = 0.001) and front-of-the-breast tenderness (p = 0.002) decreased.
Stretchy cervical mucus also decreased across the whole cycle (p = 0.048).
Flow amount and feelings of anxiety did not change between cycle 1 and cycle 6.
In the follicular phase, only fluid retention differed from the untreated baseline in cycles 3 and 6 (repeated measures ANOVA F (1.2, 14.7) = 6.7, p = 0.017).
Interpretation
The study is a single-case pilot: one woman, open-label, with self-reported diary scores and no comparison group. The authors list these limits themselves. A result like this describes what happened to one woman over six cycles. It cannot show that progesterone caused the changes, or that other women with PCOS would respond the same way. Hormone levels and other objective measures were not collected. The authors call for larger within-woman studies with objective data, and for randomized controlled trials.
RRM Context
The authors cite growing evidence that PCOS involves the brain. The hypothalamus signals the pituitary gland, and the pituitary signals the ovary. Restorative reproductive medicine also looks for the origin of irregular cycles.
Our editorial summary of this paper, not the article's abstract.
objectives: (1) changes from cycles 1 to 6 in E2-related experiences; and (2) follicular phase E2-related changes from cycle 1 (no therapy) to cycles 3 and 6.
Materials and Methods
Data from consecutive Diaries were entered into an SPSS database and analyzed by Wilcoxon Signed Rank Test (Objective #1) within-person whole cycle ordinal data, and (Objective #2 follicular phase) repeated measures ANOVA.
Results
Cyclic OMP was associated with regular, shorter cycles (±SD) (28.2 ± 0.8 days). Comparison of cycles 1-6 showed decreased fluid retention (p = 0.001), breast tenderness (p = 0.002), and cervical mucus (p = 0.048); there were no changes in flow or anxiety. Fluid retention in the follicular phase also significantly decreased over time (F (1.2, 14.7) = 6.7, p = 0.017).
Conclusions
Pilot daily Diary data suggest women with PCOS have improved everyday experiences on cyclic progesterone therapy. Larger prospective studies with more objective outcomes and randomized controlled trials of this innovative PCOS therapy are needed.
Guthardt Y et al., 2026·Sci Rep·Free full text on PubMed Central
This systematic review and meta-analysis examined the relationship between menstrual cycle phases and the incidence of muscle injuries in female team sport athletes, following PRISMA 2020 and PERSiST guidelines. A comprehensive search was conducted in PubMed, Scopus, and SPORTDiscus from inception to mid-January 2024. Studies were included if they examined female team sport athletes of reproductive age with regular menstrual cycles and compared the occurrence of muscle injuries across at least two menstrual phases. Studies involving hormonal contraceptive use, medications affecting the menstrual cycle or musculoskeletal system, or menstrual dysfunction were excluded. Three studies met the inclusion criteria, involving 318 participants. Meta-analysis yielded a pooled Risk Ratio of 1.18 (95% CI: 0.75 to 1.86, p = 0.46) for injury risk between the luteal and follicular phases, suggesting no statistically significant association. However, the certainty of the cumulative evidence was rated as very low due to methodological limitations, including inconsistent phase classifications and reliance on imprecise methods for identifying menstrual phases. Consequently, no practical or clinical recommendations can be made at this time. Future research employing standardised, physiologically accurate methods for classifying and detecting menstrual cycle phases is necessary to better understand the potential links between hormonal fluctuations and injury risk.
Shirin S et al., 2020·J Endocr Soc·Free full text on PubMed Central
Women living with androgenic PCOS (WLWP) experience unpredictable oligomenorrhea1 and are at increased risk for endometrial cancer2. Oral micronized progesterone (OMP) given cyclically (14 days/cycle or 4 weeks, Cyclic OMP), in luteal phase doses3 (300 mg at bedtime) as a “luteal phase replacement” therapy would be likely to effectively treat both. In addition, evidence suggests PCOS is causally related to rapid pulsing of GnRH and LH 4; OMP normalizes LH pulsatility if androgen levels are not elevated 4. Previous searches did not find progesterone therapy for PCOS 5. Our Does the peer-reviewed literature provide evidence for prescribing cyclic progesterone therapy in PCOS? Literature search methods used Medline (Ovid) and PubMed for published articles. Our search terms were: “polycystic ovary syndrome”, “androgenic PCOS”, and, “micronized progesterone.” We sought publications with eligible women participants having androgenic PCOS, drug exposures (cyclic
OMP, vaginal progesterone, and in varying doses and durations) and specific outcomes (biochemical or patient-reported data or both) in all languages. We excluded reviews and practice guidelines but searched bibliographies for missed citations. Results discovered 18 articles in combined Medline (n=6) and PubMed (12) searches. After excluding duplicates, articles on estradiol (E2) alone E2 with OMP therapy, five eligible articles remained. We read all in full detail.
Progesterone therapy was beneficial for WLWP as, even in sub-therapeutic doses (<300 mg at bedtime) and in cycles of too short durations (<14 days), it decreased luteinizing hormone (LH) 6,7 and total testosterone 7 levels. Vaginal progesterone (200 mg, b.i.d for 2 to 12 weeks) added to letrozole ovulation induction increased the pregnancy rate from 0 to 21% 8. Although present data suggest Cyclic OMP withdrawal predictively causes flow, we found no evidence it improved women’s cycle-related experiences nor decreased acne and hirsutism. Women-reported data on Cyclic OMP for improving androgenic PCOS cycle regularity, daily experiences and risks for endometrial cancer are needed.
To assess the effect of insulin-lowering treatment on menstrual cyclicity in polycystic ovary syndrome (PCOS). Forty oligoamenorrheic women with PCOS were recruited in a prospective clinical study to receive metformin for a minimum period of 6 months. Twenty-two women completed the study. Serum LH, FSH, free testosterone, and glucose and insulin response to oral glucose load were measured both before and after 8 weeks of metformin treatment. Menstrual cyclicity and serum progesterone levels at the midluteal phase were assessed at the 30th week of metformin treatment. Twenty-one of 22 women had restoration of menstrual cyclicity (95.7%). Four of these women (19%) became pregnant within the 6th and 7th months of treatment. All four of the pregnant women delivered, and the infants were healthy. Thirteen of 15 women who had regular menses demonstrated a serum progesterone level within the ovulatory range (3.1-28 ng/mL). Fasting (P < .001) and the integrated insulin response to the glucose load decreased (P < .001) after 8 weeks of metformin treatment. This was accompanied by significant decreases in serum LH (P < .001) and free testosterone (P < .001) levels and LH/FSH ratio (P < .001). There was a small but significant reduction in body mass index after 8 weeks of metformin treatment (P < .001). A 6-month course of metformin may improve menstrual cyclicity and fertility in women with the PCOS. Insulin-sensitizing agents provide a rational approach to the treatment of the metabolic and endocrine abnormalities in PCOS women.
Kicińska AM et al., 2023·Healthcare (Basel)·Free full text on PubMed Central
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Absent, impaired, or rare ovulation induces progesterone deficiency in the luteal phase, which is a critical problem in PCOS. A usual pattern of progesterone administration from a fixed and arbitrary pre-determined day of a menstrual cycle may preserve infertility but can easily be avoided. We present the case of a 29-year-old infertile woman who had been ineffectively treated for over two years. We introduced a line of therapy that was suited to her individual menstrual cycle by implementing biomarker recording. Supplementation based on a standardized observation of the basal body temperature (BBT) and cervical mucus stopped the vicious circle of absent ovulation and hyperandrogenism, restoring regular bleeding, ovulation cycles, and fertility. The implementation of a reliable fertility awareness method (FAM), accompanied by a standardized teaching methodology and periodic review of the observations recorded by the patient, validated through an ultrasound examination and plasma gonadotropins, estrogens, and progesterone concentrations, is key to achieving therapeutic success. The presented case is an example of a clinical vignette for many patients who have successfully managed to improve their fertility and pregnancy outcomes by applying the principles of a personalized treatment approach together with gestagens by recording their fertility biomarkers.
A Goshtasebi, D Kalidasan, F Murray, J Prior, S Shirin
PMID 34684061 34684061 DOI 10.3390/medicina57101024 10.3390/medicina57101024 Shirin et al. 2021, Shirin 2021
Cite this article
Shirin, S., Murray, F., Goshtasebi, A., Kalidasan, D., & Prior, J. C. (2021). Cyclic Progesterone Therapy in Androgenic Polycystic Ovary Syndrome (PCOS)-A 6-Month Pilot Study of a Single Woman's Experience Changes. Medicina (Kaunas, Lithuania), 57(10), 1024. https://doi.org/10.3390/medicina57101024
Shirin S, Murray F, Goshtasebi A, Kalidasan D, Prior JC. Cyclic Progesterone Therapy in Androgenic Polycystic Ovary Syndrome (PCOS)-A 6-Month Pilot Study of a Single Woman's Experience Changes. Medicina (Kaunas). 2021;57(10):1024. doi:10.3390/medicina57101024
Shirin, S., et al. "Cyclic Progesterone Therapy in Androgenic Polycystic Ovary Syndrome (PCOS)-A 6-Month Pilot Study of a Single Woman's Experience Changes." Medicina (Kaunas, Lithuania), vol. 57, no. 10, 2021, pp. 1024.
