(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.
cyclic progesterone therapy PCOS, androgenic PCOS treatment, oral micronized progesterone PCOS, endometrial cancer prevention PCOS, neuroendocrine origins PCOS reversal, progesterone withdrawal bleeding, PCOS pilot study progesterone, menstrual cycle diary PCOS, fluid retention progesterone, breast tenderness progesterone therapy
PMID 34684061 34684061 DOI 10.3390/medicina57101024 10.3390/medicina57101024
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.
This clinical trial aims to compare hormonal and metabolic changes after a 9-week continuous use of oral or vaginal combined hormonal contraceptives (CHCs) in women with polycystic ovary syndrome (PCOS). We recruited 24 women with PCOS and randomized them to use either combined oral (COC, n = 13) or vaginal (CVC, n = 11) contraception. At baseline and 9 weeks, blood samples were collected and a 2 h glucose tolerance test (OGTT) was performed to evaluate hormonal and metabolic outcomes. After treatment, serum sex hormone binding globulin (SHBG) levels increased (p < 0.001 for both groups) and the free androgen index (FAI) decreased in both study groups (COC p < 0.001; CVC p = 0.007). OGTT glucose levels at 60 min (p = 0.011) and AUCglucose (p = 0.018) increased in the CVC group. Fasting insulin levels (p = 0.037) increased in the COC group, and insulin levels at 120 min increased in both groups (COC p = 0.004; CVC p = 0.042). There was a significant increase in triglyceride (p < 0.001) and hs-CRP (p = 0.032) levels in the CVC group. Both oral and vaginal CHCs decreased androgenicity and tended to promote insulin resistance in PCOS women. Larger and longer studies are needed to compare the metabolic effects of different administration routes of CHCs on women with PCOS.
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.
Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce gastrointestinal side effects. Inositols have long been debated as a potential alternative for metformin in treating PCOS. Therefore, the present systematic review aimed to evaluate the efficacy and safety of inositols in treating PCOS. The present systematic search was performed in CENTRAL, MEDLINE, and Embase from the inception until October 20th, 2021. Eligible randomized controlled trials (RCTs) included women diagnosed with PCOS and compared any inositols with metformin or placebo. Our primary outcome was cycle normalization, whereas secondary outcomes were body mass index (BMI), parameters of carbohydrate metabolism and clinical and laboratory hyperandrogenism. Results are reported as risk ratios or mean differences (MDs) with 95% confidence intervals (CIs). Twenty-six RCTs were identified, including data of 1691 patients (806 inositol, 311 with placebo, and 509 metformin groups). In patients treated with inositols, the risk (CI: 1.13; 2.85) of having a regular menstrual cycle was found by 1.79 higher than in the case of placebo. Moreover, the inositols showed non-inferiority compared to metformin in this outcome. In the case of BMI (MD = -0.45; CI: -0.89; -0.02), free testosterone (MD = -0,41, CI: -0.69; -0.13), total testosterone (MD = -20.39, CI: -40.12; -0.66), androstenedione (MD = -0.69, CI: -1,16; -0.22), glucose (MD = -3.14; CI: -5.75; -0.54) levels and AUC insulin (MD = -2081.05, CI: -2745.32; -1416.78) inositol treatment induced greater decrease compared to placebo. Inositol increased sex-hormone-binding globulin significantly compared to placebo (MD = 32.06, CI:1.27; 62.85). Inositol is an effective and safe treatment in PCOS. Moreover, inositols showed non-inferiority in most outcomes compared to the gold standard treatment; metformin. PROSPERO CRD42021283275.
What is the feasibility of a prospective protocol to follow subfertile couples being treated with natural procreative technology for up to 3 years at multiple clinical sites? Overall, clinical sites had missing data for about one-third of participants, the proportion of participants responding to follow-up questionnaires during time periods when participant compensation was available (about two-thirds) was double that of time periods when participant compensation was not available (about one-third) and follow-up information was most complete for pregnancies and births (obtained from both clinics and participants). Several retrospective single-clinic studies from Canada, Ireland and the USA, with subfertile couples receiving restorative reproductive medicine, mostly natural procreative technology, have reported adjusted cumulative live birth rates ranging from 29% to 66%, for treatment for up to 2 years, with a mean women's age of about 35 years. The international Natural Procreative Technology Evaluation and Surveillance of Treatment for Subfertility (iNEST) was designed as a multicenter, prospective cohort study, to enroll subfertile couples seeking treatment for live birth, assess baseline characteristics and follow them up for up to 3 years to report diagnoses, treatments and outcomes of pregnancy and live birth. In addition to obtaining data from medical record abstraction, we sent follow-up questionnaires to participants (both women and men) to obtain information about treatments and pregnancy outcomes, including whether they obtained treatment elsewhere. The study was conducted from 2006 to 2016, with a total of 10 clinics participating for at least some of the study period across four countries (Canada, Poland, UK and USA). The 834 participants were subfertile couples with the woman's age 18 years or more, not pregnant and seeking a live birth, with at least one clinic visit. Couples with known absolute infertility were excluded (i.e. bilateral tubal blockage, azoospermia). Most women were trained to use a standardized protocol for daily vulvar observation, description and recording of cervical mucus and vaginal bleeding (the Creighton Model FertilityCare System). Couples received medical and sometimes surgical evaluation and treatments aimed to restore and optimize female and male reproductive function, to facilitate in vivo conception. MAIN The mean age of women starting treatment was 34.0 years; among those with additional demographic data, 382/478 (80%) had 16 or more years of education, and 199/659 (30%) had a prior live birth. Across 10 clinical sites in four countries (mostly private clinical practices) with family physicians or obstetrician-gynecologists, data about clinic visits were submitted for 60% of participants, and diagnostic data for 77%. For data obtained directly from the couple, 59% of couples had at least one follow-up questionnaire, and the proportion of women and men responding to fill out the follow-up questionnaires was 69% and 67%, respectively, when participant financial compensation was available, compared to 38% and 33% when compensation was not available. Among all couples, 57% had at least one pregnancy and 44% at least one live birth during the follow-up time period, based on data obtained from clinic and/or participant questionnaires. All sites reported on female pelvic surgical procedures, and among all participants, 22% of females underwent a pelvic diagnostic and/or therapeutic procedure, predominantly laparoscopy and hysterosalpingography. Among the 643 (77%) of participants with diagnostic information, ovulation-related disorders were diagnosed in 87%, endometriosis in 31%, nutritional disorders in 47% and abnormalities of semen analysis in 24%. The mean number of diagnoses per couple was 4.7. LIMITATIONS The level of missing data was higher than anticipated, which limits both generalizability and the ability to study different components of treatment and prognosis. Loss to follow-up may also be differential and introduce bias for outcomes. Most of the participating clinicians were not surgeons, which limits the opportunity to study the impact of surgical interventions. Participants were geographically dispersed but relatively homogeneous with regard to socioeconomic status, which may limit the generalizability of current and future findings. Multicenter studies are key to understanding the outcomes of subfertility treatments beyond IVF or IUI in broader populations, and the association of different prognostic factors with outcomes. We anticipate that the iNEST study will provide insight for clinical and treatment factors associated with outcomes of pregnancy and live birth, with appropriate attention to potential biases (including adjustment for potential confounders, multiple imputation for missing data, sensitivity analysis and inverse probability weighting for potential differential loss to follow-up, and assessments for clinical site heterogeneity). Future studies adequate funding to compensate clinics and participants for robust data collection, including targeted randomized trials; or a scaled-down, registry-based approach with targeted data points, similar to the multiple national and regional ART registries. Funding for the study came from the International Institute for Restorative Reproductive Medicine, the University of Utah, Department of Family and Preventive Medicine, Health Studies Fund, the Primary Children's Medical Foundation, the Mary Cross Tippmann Foundation, the Atlas Foundation, the St. Augustine Foundation and the Women's Reproductive Health Foundation. The authors declare no competing interests. The iNEST study is registered at clinicaltrials.gov, NCT01363596.