Sonia Shirin

MON-154 Breast areolar diameter in healthy menstruating women—a single cycle cross-sectional study of associations with body size and ovulatory characteristics

Baaske AV et al., 2025 · Journal of the Endocrine Society · Open Access

A.V. Baaske: None. S. Shirin: None. C. Bos: None. D. Kalidasan: None. J.C. Prior: None. Tanner Breast Stage 3 (TB3, at menarche) and Tanner 5 (TB5, once ovulatory cycles established), despite being similar with an “upstanding” nipple, are different. Evidence suggests that steady and high ovulatory-level progesterone exposure accounts for the larger areolar diameter in TB5. Progesterone levels indicate whether the menstrual cycle is ovulatory and have crucial implications for women’s reproductive, metabolic, cardiovascular, and bone health. However, few data show average areolar diameter in regularly cycling women in whom SES, body size, and reproductive variables have been documented. As a step towards better understanding the role of areolar diameter in reflecting estradiol-progesterone balance, this study aims to document the average mean bilateral lateral areolar diameter (AD) in a cohort of regularly menstruating, premenopausal women in whom ovulation was documented in one cycle. We also aim to describe relationships between AD and demographic, anthropometric, and reproductive/ovulation variables. Women were eligible if aged 19-35 years with about month-apart cycles and no exogenous hormone use in the last 3-months. Participants completed one cycle with a daily Menstrual Cycle Diary© (cycle length, CL) and first morning temperatures for Quantitative Basal Temperature© (QBT©) ovulation analysis (normal luteal phase length ≥10 days). Questionnaires gathered SES, ethnic, general health, and reproductive characteristics. Bilateral horizontal areolar diameters were measured by a woman researcher with the participant supine in a warm room. From February 2020 to September 2022 (during the SARS-CoV-2 pandemic), 73 women from Metro Vancouver, British Columbia participated. Women were of median (min-max) age 30 (19-35) years, BMI 24.5 (17.1-41.4) and most identified as White (61.6%) with a median of 16 years of education. Median CL was 29 days (n=65) and QBT data showed 39.3% were normally ovulatory, 34.4% had short luteal phases and 26.2% were anovulatory. Median within-woman bilateral AD was 3.85 (2.35-8.00) cm. Left AD exceeded right (L 3.8 [2.3,8.2]; R 3.7 [ 2.4,7.8]; P=.003). Larger AD (≥3.85cm) was associated with greater body size (BMI r=.534), weight and waist circumference. However, earlier age at menarche (P=.02) was also significantly associated. No other reproductive variables (cycle length, luteal phase length, parity, ever use of CHC) were related to AD before body size adjustments. This study is the first to document, and describe demographic, anthropomorphic and reproductive associations with, AD in community dwelling, regularly cycling, premenopausal women. Future steps will determine the most influential of the anthropometric variables; adjustment for these will facilitate assessments of associations with ovulation related characteristics. Presentation: Monday, July 14, 2025

SAT-128 Prospective 1-year Menstrual CycleBreast Tenderness and Swelling Experiences—data from healthy regularly cycling women initially proven normally ovulatory on two consecutive cycles

Wood M et al., 2025 · Journal of the Endocrine Society · Open Access

M. Wood: None. J.C. Prior: None. S. Shirin: None. A. Goshtasebi: None. Breast tenderness and swelling are associated with premenstrual symptoms but have not been well described in healthy, normally cycling women with known ovulatory status. There are documented negative health risks (in bone, the cardiovascular system and cancers) in association with ovulatory disturbances within normal-length cycles. Identifying breast changes across a predictable, month-apart cycle but with Subclinical Ovulatory Disturbances (SOD, short luteal phase [<10 days] and anovulation (with normal estradiol but lower or absent progesterone levels) could advance our understanding of menstrual cycle physiology, women’s health education and identification of those with chronic SOD who may benefit from cyclic progesterone therapy. Our objective was to determine whether within-woman breast tenderness and swelling experiences differed between normally ovulatory and ovulatory-disturbed cycles. In this 1-year prospective observational study, we examined daily breast tenderness (0-4) and swelling (1-5 change from usual = 3) experiences recorded via the Menstrual Cycle Diary© over ≥8 cycles (mean=13/woman) in 53 women. Ovulatory status was documented by the twice-validated Quantitative Basal Temperature© (QBT©) analysis. Cycle and ovulatory data were previously reported (Prior NEJM, 1990); Diary data were unreported. Participants were healthy, community-dwelling women, mean age 34 (32.4:35.5 years), BMI 22.0, primarily White, and about two-thirds were runners (for health or were marathon-training). Comparison of breast parameters in all normally ovulatory (n = 495) vs all SOD cycles (n = 199) (mean cycle length 28.1 [27.5-28.8 days]), showed significantly higher Breast Tenderness Score [intensity X days; 6.0 (range 1.0, 14.0) vs. 3.0 (0.0, 11.0) (P = .001)] and increased breast size [4.0 (2.0, 4.0) vs. 4.0 (0.0, 4.0) (P = .034]) in normally ovulatory cycles. However, in within-woman analysis (n = 47 women with both normally ovulatory and SOD cycles), breast tenderness/swelling did not significantly differ by ovulatory status. We plotted all ovulatory cycles (n=676) centred on ovulation; this revealed parallel timing of increases in breast tenderness and swelling in the late luteal phase. These 1-year prospective data documented that mild breast tenderness and swelling occurred before flow in cycles with normal ovulation; symptoms were less in SOD cycles. Breast changes were totally absent during the follicular phases. Presentation: Saturday, July 12, 2025

Feeling of self-worth in healthy premenopausal women-relationships with menstrual cycles and ovulation over 1-year in the prospective ovulation cohort

Shirazian N et al., 2025 · PLoS One · Open Access

Self-Worth is an over-arching evaluation of a person's sense of individual value. Self-worth, however, is an underappreciated concept. It has rarely been reported related to physiological data; we found no studies related to the menstrual cycle or ovulation. It is also unclear if Self-Worth is a stable trait or a variable state. We sought to discover if "Feeling of Self-Worth" (as recorded daily) was related to cycle phases and ovulation of spontaneous menstrual cycles (without hormonal contraception) in healthy premenopausal women over one-year in data from the Prospective Ovulation Cohort. Participating women were invited to complete the Menstrual Cycle Diary© (Diary©) daily; it describes cycle-related and other comprehensive everyday life experiences including negative moods as well as changes from each person's usual Feelings of Self-Worth. Women recorded their Feeling of Self-Worth on a 5-level ordinal scale as a letter translated to a number originally centered on their usual feeling (U = 3) with two higher and two lower (letters) levels. The validated Quantitative Basal Temperature© (QBT©) method was used to assess ovulation and luteal lengths. Fifty-three healthy, community dwelling, normal-weight, non-smoking premenopausal women mean age 33.9 (95% CI 32.4, 35.5) years old were studied. All participants were first required to document two consecutive normal-length (21-36 days) and normally ovulatory (luteal length ≥10 days) cycles before enrolment. Each participant completed the Diary© and QBT© records daily over a mean of 13 cycles (minimum = 8). During the study, cycle lengths were mean 28.04 (95% CI 27.80, 28.28) days with 71% of all cycles being normally ovulatory, 26% having short luteal phases (SLP, LL < 10 days) and 2.6% being anovulatory. Results in all women and all cycles showed that the mean annual Feeling of Self-Worth was 3.01 (95% CI 2.94, 3.09), thus very tightly related to their usual Feeling of Self-Worth. There were only small, inconsistent differences between Feeling of Self-Worth in the follicular versus luteal phases comparing normally ovulatory versus all ovulatory cycles (including those with short luteal phases). Analysis of Self-Worth within the 46 women having both normally ovulatory and ovulatory disturbed cycles (short luteal and anovulatory) showed that it was slightly lower in these women's normally ovulatory cycles (P = .03). Principal Components Analysis of all Diary© data showed that Feeling of Self-Worth was positively related to Interest in Sex and Feeling of Energy (together explaining 9% of all variance). In addition, Feeling of Self-Worth had a significant, negative loading on the Negative Mood Factor (that explained 14.2% of total variance). These data suggest that Feelings of Self-Worth in this comprehensive menstrual cycle and ovulation dataset in healthy women were not related menstrual phases and ovarian hormone levels.

Ovulatory and anovulatory cycle phase influences on QT interval dynamics during the menstrual cycle

Naderi B et al., 2025 · PLoS One · Open Access

Ovarian hormones affect cardiovascular health yet few sufficient-sized studies with reliable ovulatory documentation have assessed the QTc-hormonal relationship. This study investigated QTc changes across ovulatory and anovulatory menstrual cycle phases. This prospective cohort investigation, a cardiac sub-study of the Menstruation and Ovulation Study 2 (MOS2), involved 62 healthy, regularly menstruating community-dwelling women during spontaneous menstrual cycles. Electrocardiographic recordings were obtained within-woman during different cycle phases: mid-follicular for all, and luteal (ovulatory) or premenstrual (anovulatory), documented by the validated Quantitative Basal Temperature© method. Fridericia's formula rate-corrected the QT interval (QTc). A subsequent meta-analysis was conducted, pooling data from three additional studies to evaluate ovulatory follicular-luteal phase QTc changes. In the 26 ovulatory cycles, QTc minimally decreased from the mid-follicular to the luteal phases (383.0 ± 12.8 vs 382.6 ± 12.8 msec, P = .859). QTc in the 36 anovulatory cycles tended to increase from mid-follicular to premenstrual phases (381.7 ± 13.1 vs 385.0 ± 16.1 msec, P = .166). The meta-analysis in ovulatory cycles yielded a random-effects weighted mean QTc shortening of 1.67 msec (P = .53) in the luteal vs the follicular phase, aligning with our cohort data. In confirmed ovulatory cycles, QTc changes were minimal, showing no meaningful luteal phase QTc shortening. QTc changes in anovulatory cycles were also insignificant, with a small QTc prolongation likely due to longer estradiol exposure not counterbalanced by progesterone. Under normal physiological conditions, QTc changes during the menstrual cycle are trivial, and menstrual status does not need to be considered when interpreting the QT interval.

Breast tenderness and swelling experiences related to menstrual cycles and ovulation in healthy premenopausal women: Secondary analysis of the 1-year "Prospective Ovulation Cohort"

Wood M et al., 2025 · PLoS One · Open Access

Breast tenderness and swelling are associated with premenstrual symptoms but are not well described in healthy women. In this 1-year prospective observational study, we examined daily breast tenderness and swelling to determine whether differences existed between normally ovulatory and ovulatory disturbed (short luteal phase and anovulatory) cycles in a cohort of community dwelling, non-smoking, healthy premenopausal women. Enrolment required two consecutive normal-length and normally ovulatory cycles by Quantitative Basal Temperature© analysis. Women (n = 53) ages 20-41 recorded their daily breast experiences in the Menstrual Cycle Diary© across an average of 13.6 cycles. In all 720 cycles, the median breast tenderness was 1.4 (on a 0-4 scale, range 0.0-3.0), in cycles with a mean length of 28.1 days (95% CI 27.5-28.8). Comparison of breast tenderness and breast size (changes from usual) parameters between all normally ovulatory cycles and all ovulatory disturbed cycles in the whole cohort showed significantly higher levels in normally ovulatory (luteal length ≥10 days) in both Breast Tenderness Score [intensity X duration in days; 6.0 (range 1.0-14.0) vs. 3.0 (0.0-11.0) (P=.005)] and breast size [4.0 (2.0-4.0) vs. 4.0 (0.0-4.0) (P=.034]). However, within-woman in the forty-seven women with both normally ovulatory and ovulatory disturbed cycles, breast tenderness (intensity, duration, and Breast Tenderness Score), did not differ between normally ovulatory cycles and cycles with ovulatory disturbances. This study also demonstrated that in all ovulatory cycles, the timing of breast tenderness increased in parallel with breast swelling; the maximum for both was in the late luteal phase.

Prospective 1-year assessment of within-woman variability of follicular and luteal phase lengths in healthy women prescreened to have normal menstrual cycle and luteal phase lengths

Henry S et al., 2024 · Hum Reprod · Open Access

What is the relative length variance of the luteal phase compared to the follicular phase within healthy, non-smoking, normal-weight, proven normally ovulatory, premenopausal women with normal-length menstrual cycles? Prospective 1-year data from 53 premenopausal women with two proven normal-length (21-36 days) and normally ovulatory (≥10 days luteal) menstrual cycles upon enrollment showed that, despite 29% of all cycles having incident ovulatory disturbances, within-woman follicular phase length variances were significantly greater than luteal phase length variances. Many studies report menstrual cycle variability, yet few describe variability in follicular and luteal phase lengths. Luteal lengths are assumed 'fixed' at 13-14 days. Most studies have described follicular and luteal phase variability between-women. STUDY DESIGN, SIZE, Duration: This study was a prospective, 1-year, observational cohort study of relative follicular and luteal phase variability both between and within community-dwelling women with two documented normal-length (21-36 days) and normally ovulatory (≥10 days luteal phase) menstrual cycles prior to enrollment. Eighty-one women enrolled in the study and 66 women completed the 1-year study. This study analyzed data from 53 women with complete data for ≥8 cycles (mean 13). PARTICIPANTS/MATERIALS, SETTING, Participants were healthy, non-smoking, of normal BMI, ages 21-41 with two documented normal-length (21-36 days) and normally ovulatory (≥10 days luteal phase) menstrual cycles prior to enrollment. Participants recorded first morning temperature, exercise durations, and menstrual cycle/life experiences daily in the Menstrual Cycle Diary. We analyzed 694 cycles utilizing a twice-validated least-squares Quantitative Basal Temperature method to determine follicular and luteal phase lengths. Statistical analysis compared relative follicular and luteal phase variance in ovulatory cycles both between-women and within-woman. Normal-length cycles with short luteal phases or anovulation were considered to have subclinical ovulatory disturbances (SOD). Main The 1-year overall 53-woman, 676 ovulatory cycle variances for menstrual cycle, follicular, and luteal phase lengths were 10.3, 11.2, and 4.3 days, respectively. Median variances within-woman for cycle, follicular, and luteal lengths were 3.1, 5.2, and 3.0 days, respectively. Menstrual cycles were largely of normal lengths (98%) with an important prevalence of Sod: 55% of women experienced >1 short luteal phase (<10 days) and 17% experienced at least one anovulatory cycle. Within-woman follicular phase length variances were greater than luteal phase length variances (P < 0.001). However, follicular (P = 0.008) and luteal phase length (P = 0.001) variances, without differences in cycle lengths, were greater in women experiencing any anovulatory cycles (n = 8) than in women with entirely normally ovulatory cycles (n = 6). LIMITATIONS, Limitations of this study include the relatively small cohort, that most women were White, initially had a normal BMI, and the original cohort required two normal-length and normally ovulatory menstrual cycles before enrollment. Thus, this cohort's data underestimated population menstrual cycle phase variances and the prevalence of SOD. Our results reinforce previous findings that the follicular phase is more variable than the luteal phase in premenopausal women with normal-length and ovulatory menstrual cycles. However, our study adds to the growing body of evidence that the luteal phase is not predictably 13-14 days long. STUDY FUNDING/COMPETING INTEREST(S): This medical education project of the University of British Columbia was funded by donations to the Centre for Menstrual Cycle and Ovulation Research. The authors do not have any conflicts of interest to disclose. N/A.

Menstrual Cramps in Anovulatory versus Normally Ovulatory Cycles - SARS-COV-2 Pandemic Daily Data Plus a Meta-Analysis of Cramps and Anovulation

Mann G et al., 2024 · J Pain Res · Open Access

It is asserted that primary dysmenorrhea/menstrual cramps only occur in ovulatory menstrual cycles. Our first objective was to present detailed menstrual cramps information in normally ovulatory versus anovulatory cycles from a single-cycle cohort study during the SARS-CoV-2 Pandemic. Secondly, we reviewed the literature for cohort studies documenting both menstrual cramps and ovulation. Participants and The Menstruation and Ovulation Study 2 recruited 108 women ages 19-35 years to a prospective, observational single-cycle study, recording cramps daily (0-4 scale) in the Menstrual Cycle Diary© and assessing normal ovulation (luteal length ≥10 days) by the validated Quantitative Basal Temperature© (Mean Temperature Method). We searched databases for « primary dysmenorrhea » / » menstrual cramps »; « menstrual cycles »; « anovulation », finding four valid publications. In 75 women/cycles during the Pandemic, mean age was 28.5, body mass index 23.5, and higher education (16 years); 40 normally ovulatory and 35 anovulatory cycles had similar lengths (29.5-30.0 days), respectively (P=0.571). However, anovulatory cycles recorded significantly worse menstrual cramps versus normally ovulatory cycles; anovulatory median intensity was 1.9 versus 1.6, and Cramp Score was 8 versus 6 in normally ovulatory cycles (P=0.017). Four publications in 273 women (991 cycles) showed cramps in both anovulatory and ovulatory cycles; three were in adolescent/young adult women, one of which documented a significantly greater percentage of cramps in ovulatory cycles. The 694 cycles in premenopausal women (20-41 years) showed similar percentages of symptomatic cramps in cycles of both ovulatory types. Meta-analysis documented significantly higher cramp prevalence in ovulatory cycles (OR 2.10; 95% CI 1.31, 3.37; P=0.002). This is the first documentation of more intense and frequent cramps in anovulatory cycles. However, meta-analysis showing the presence of symptomatic cramps in both ovulatory and anovulatory cycles documented they were twice as prevalent in ovulatory menstrual cycles. “Worse Menstrual Cramps in Anovulatory Cycles”. Medicine has long believed that menstrual cramps only occur in ovulatory menstrual cycles that release an egg and have high progesterone levels that decrease before the next period. The notion was that dropping progesterone levels triggered release of prostaglandins that cause the pain and uterus muscle contractions of menstrual cramps. This research studied 75 community women aged 19–35 years for a single cycle during COVID-19. Forty women had normally ovulatory cycles and 35 had anovulatory cycles with a similar mean cycle length of 29.7 days. Women in both groups were similar in age, weight, education and other reproductive characteristics. Women recorded Menstrual Cycle Diary© daily experiences for cramp presence and intensity (scored 0–4). Ovulation was documented by daily first morning temperatures analyzed by the valid Quantitative Basal Temperature© method. Results showed menstrual cramps occurred in both normally ovulatory and anovulatory cycles. Surprisingly, anovulatory compared with ovulatory cycles had cramps that lasted longer (4 rather than 3 days), were more intense (1.9 versus 1.6) and with significantly higher Cramp Scores (of 8 versus 6). We also found four other published studies showing cramps occurred in both anovulatory and ovulatory cycles. A meta-analysis of these, however, showed that cramps were twice as frequent in ovulatory cycles. These results matter because they stimulate the search for more accurate understandings of why menstrual cramps occur. They will likely stimulate more effective therapies for the rare, intense menstrual cramps that currently are not effectively treated by anti-inflammatory medicines such as ibuprofen.

Experiences of women living with Polycystic Ovary Syndrome: A pilot case-control, single-cycle, daily Menstrual Cycle Diary study during the SARS-CoV-2 pandemic

Nelson K et al., 2024 · PLoS One · Open Access

Polycystic Ovary Syndrome (PCOS) affects many people and is often distressing. Much medical literature about diagnosis and treatment exists, but little is known about PCOS menstrual cycle-related experiences except that cycles tend to be far-apart and unpredictable. Our purpose was to examine the menstrual cycle and daily life experiences in those with PCOS having approximately month-apart cycles compared with age and BMI-matched cohort controls using data from the Menstruation & Ovulation Study 2 (MOS2) during the first 1.5 years of SARS-CoV-2 pandemic. We hypothesized that those with PCOS would experience lower self-worth and more negative moods. This is a single-cycle prospective case-control study in community-dwelling women ages 19-35 years. Eight reported physician-diagnosed PCOS and were matched (1:3 ratio) with controls by age (within .6 years) and BMI (within .19 BMI units). Experiences were recorded daily (Menstrual Cycle Diary©, Diary). All kept daily morning temperatures to assess luteal phase lengths by the validated Quantitative Basal Temperature© analysis method. From 112 in MOS2, 32 women were compared: eight with PCOS versus 24 controls. Demographic, socioeconomic, comorbidities and lifestyle variables were not different between the two groups. Cycle lengths were similar in PCOS and controls (one PCOS and control each had oligomenorrhea; most lengths were 21-35 days, P = .593). Unexpectedly, luteal phase lengths were also similar between PCOS and controls (P = .167); anovulation occurred in 5 with PCOS, and in 9 controls. There were no significant Diary differences between the two groups except for greater "outside stress" in the PCOS group (P = .020). In contrast to our hypotheses, there were no significant differences in feelings of self-worth, anxiety nor depression. The SARS-CoV-2 pandemic was a stressful time for women. MOS2 captured granular menstrual cycles, ovulation and daily experiences in women with PCOS compared with ageand BMI-matched controls. These pilot data in women with milder PCOS are the first of more research required to understand the daily experiences in those living with PCOS.

Don't ignore perimenopause

Prior JC et al., 2023 · CMAJ · Open Access

We agree with Lega and colleagues[1][1] that menopausal hormone therapy (MHT) has been shown in randomized controlled trials (RCTs) to be effective and safe for treating problematic vasomotor symptoms related to menopause. We also agree that treating menopausal vasomotor symptoms is important to

Bone health and prevalent fractures in women with polycystic ovary syndrome: a meta-analysis and endocrine-context pathophysiology review

Prior JC et al., 2023 · Expert Rev Endocrinol Metab ·

Bone health in those with Polycystic Ovary Syndrome (PCOS) is complex, but the general consensus is that cortical areal bone mineral density (aBMD) sites will be higher in PCOS than in ageand BMI-similar controls. However, spine aBMD sites may be lower, especially in non-obese PCOS. Whether or not incident fracture risk is increased in PCOS is currently controversial; no meta-analysis has yet assessed prevalent fractures. We assessed the bone effects of PCOS-related ovarian hormone alterations, e.g. androgen excess, tonically normal/higher estradiol, and lower-than-normal progesterone levels. We also highlighted evidence that common PCOS medications (e.g. combined hormonal contraceptives [CHC], metformin, and spironolactone) have important bone effects. In adolescents, meta-analysis of CHC showed significant negative aBMD changes. Inflammation has negative PCOS bone effects and is linked with CHC use. EXPERT Opinion: Is fracture risk altered by PCOS? Our meta-analysis showed a 25% increased risk of prevalent fracture in PCOS versus controls; this did not reach statistical significance. Future prospective research needs to collect and evaluate ovulation characteristics, progesterone exposure, and adolescent CHC use, in addition to the complex variables that may influence risks for prevalent or incident fragility fractures and/or for cortical and cancellous aBMD values in PCOS.

Cyclic Progesterone Therapy in Androgenic Polycystic Ovary Syndrome (PCOS)-A 6-Month Pilot Study of a Single Woman's Experience Changes

Shirin S et al., 2021 · Medicina (Kaunas) · Open Access

Women with androgenic Polycystic Ovary Syndrome (PCOS) have increased endometrial cancer risk that cyclic progesterone will prevent; it may also reverse PCOS's neuroendocrine origins. This pilot study's purpose was to document 6-month experience changes in a woman with PCOS taking cyclic progesterone therapy because she was intolerant of combined hormonal contraceptive therapy, the current PCOS standard of care. A 31-year-old normal-weight woman with PCOS had heavy flow, irregular cycles, and was combined hormonal contraceptives-intolerant. She was prescribed cyclic oral micronized progesterone (OMP) (300 mg/h.s. cycle days 14-27). She kept Menstrual Cycle Diary© (Diary) records, starting with the 1st treatment cycle for six cycles; she was on no other therapy. Statistical analysis a priori hypothesized progesterone decreases high estradiol (E2) experiences (flow, cervical mucus, fluid retention, front-of-the-breast tenderness and anxiety); analysis focused on these. Our (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. 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. 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). 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.

"Phase II 6-month Cyclic Progesterone/Spironolactone pilot Therapy Trial in Polycystic Ovary Syndrome : pre-post, single-arm feasibility study"

Prior JC et al., 2021 · Open Collections ·

Androgenic Polycystic Ovary Syndrome (PCOS) creates physical/emotional burdens in 4-20% of premenopausal women living with PCOS (WLWP) including: few menstruations per year, subfertility, hirsutism/acne and low quality of life by validated PCOS Questionnaire (PCOSQ). Combined hormonal contraceptives (CHC), the current standard-of-care, improve PCOSQ only 16%; with stopping CHC, benefits disappear within 6-months. We hypothesize too-fast brain/luteinizing hormone (LH) pulses cause PCOS. Progesterone (P4) slows LH when testosterone (FreeT) is normal. Combining two approved medications, Cyclic P4 with anti-androgen, Spironolactone (Sp), will likely provide effective, durable benefits. WLWP lit-review suggested significant P4 7-14-day benefits. A 6-month prospective feasibility study of CyclicP4/Sp is necessary. Overall Perform a pilot study in 40 WLWP on Cyclic P4 (300 mg/bedtime, 14 days/month) plus Spironolactone (Sp, 200 mg/d). Feasibility: Assess longitudinal within-WLWP 6-month changes in: 1) PCOSQ; 2) FreeT, HbA1c, and LH; plus 3) WLWP's acceptance of CyclicP4/Sp. Single-centre, prospective, longitudinal single cohort study. Recruit \~7-8 WLWP/month over 4-6 months; 85% retention. Eligible WLWP have physician-diagnosed PCOS, are 1-month off CHC/metformin, ages 19-35 (avoiding adolescence/perimenopause), HbA1c <6.4% (no diabetes) and commit to non-hormonal contraception, if needed. Recruitment uses online, internet, strategic ads and tear-tab posters. Measures at 0 and 6 months: as above plus K+ (safety assessment). Menstrual Cycle Diary monitoring (flow, adherence), 2 visits, monthly telephone/emails for support and assessment of any adverse effects. Statistical analysis: changes by paired T-test. A feasibility 6-month study of CyclicP4/Sp will facilitate a CIHR-funded RCT of CHC versus this innovative and likely beneficial treatment for WLWP.

MON-LB9 Cyclic Progesterone Therapy in Androgenic Polycystic Ovary Syndrome (PCOS) - Person-Related 6-Month Experience Changes

Shirin S et al., 2020 · J Endocr Soc · Open Access

Endometrial cancer1 and oligomenorrhea2 are common risks for women living with androgenic PCOS (WLWP); cyclic progesterone therapy could prevent both. Cyclic oral micronized progesterone therapy (Cyclic OMP; 300 mg at hs/14 days/cycle) also corrects the neuroendocrine origins of PCOS3. Although vaginal progesterone is used in PCOS ovulation induction 4, and short Cyclic OMP decreases LH and/or Testosterone 5,6, no WLWP person-level prospective data with Cyclic OMP therapy are published. A WLWP, aged 31, BMI 20.1, with heavy flow and slightly irregular \~35-day cycles, was unable to tolerate birth control pills. She was prescribed Cyclic OMP (300 mg/h.s. cycle days 14-27)7. She began keeping the Menstrual Cycle Diary© (Diary), a 19-item tool (scored 0-4), during her 1st Cyclic OMP cycle and took no other therapy. This pilot study was designed to understand Cyclic OMP-related experience changes in Wlwp: 1) by documenting experience changes on the 1st to the 6th complete Diary; and 2) by assessing follicular phase changes in baseline data (no Rx) vs. cycles 3 and 6. We entered data from six consecutive Diaries into an SPSS (Version 24) database. Analysis #1 used Wilcoxon Signed Ranks Tests (for within-person ordinal data) and #2 repeated measures ANOVA. What Cyclic OMP-related experience changes occurred for a WLWP? On Cyclic OMP, she spontaneously reported improvements in aching joints, sleep and GI problems. We assessed selected, potentially E2-related Diary changes: flow, fluid retention, breast tenderness, stretchy cervical mucus and anxiety. Cyclic OMP was associated with shorter cycle lengths of 28.17+/-0.8 days. Fluid retention (P=0.000), mucus (P=0.048), and breast tenderness (P=0.000) all decreased, but anxiety and flow were unchanged. Follicular phase only fluid retention significantly decreased (F (1.2, 14.7) = 6.7, P =0.017). Although open-label, these prospective analyses suggest that Cyclic OMP, alone, is related to short-term benefits in androgenic PCOS. Prospective studies and controlled comparative trials of this innovative “luteal phase replacement” PCOS therapy are needed. Reference:1Barry J Hum Reprod Update 2014 20:748. 2Azziz R Nat Rev Dis Primers 2016;2:16057. 3Blank S Hum Reprod Update 2006;12:351. 4Montville C Fertil Steril 2010;94:678. 5Livadas S Fertil Steril 2010;94:242. 6Bagis T J Clin Endocr Met 2002;87:4536. 7Prior J https://hellocluecom/articles/cycle-a-z/the-case-for-a-new-pcos-therapy 2018

MON-LB010 Cyclic Progesterone Therapy for Androgenic Polycystic Ovary Syndrome (PCOS) - A Systematic Review of the Literature

Shirin S et al., 2020 · J Endocr Soc · Open Access

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. Reference: 1Azziz R Nat Rev Dis Primers 2016;2:16057. 2Barry J Hum Reprod Update 2014; 20:748. 3Simon J Fertil Steril 1993;60:26. 4Blank S Hum Reprod Update 2006;12:351. 5Teede H Clin Endocrinol (Oxf) 2018;89:251. 6Livadas S Fertil Steril 2010;94:242. 7Bagis T J Clin Endocr Met 2002;87:4536. 8Montville C Fertil Steril. 2010;94:678.

The central role of ovulatory disturbances in the etiology of androgenic polycystic ovary syndrome (PCOS)—Evidence for treatment with cyclic progesterone

Briden L et al., 2020 · Drug Discovery Today: Disease Models ·

Menstrual cycle phases and exposure to environmental contaminants : Menstrual Cycle and Ovulation Study 2 (MOS2)

Prior JC et al., 2020 · Open Collections ·

In 2006-2008, 610 premenopausal, spontaneously menstruating women in the Metro Vancouver region participated in a Canadian Institutes of Health Research (CIHR)-funded singlecycle in which they collected first morning urine specimens for estrogen and progesterone metabolites1. Following that study, after analyses, we retrieved the remaining urine specimens from the analyzing laboratory (University of Washington). We sorted data so that samples from all those women who were anovulatory by the two combined urinary steroid evaluation methods2,3, plus from those who were ovulatory with the highest and the lowest urinary hormone values were shipped to Health Canada (HC) via Dr. Warren Foster’s laboratory at McMaster University. Those data on flame retardant contaminants in women’s urine have been published4, but the cycle-phase specific data are still in analysis (personal communication, S Kalyan, 2019). In 2017, HC basic scientists launched applications to HC to fund a similar study to assess flame retardant excretory changes in the same population/locale 10 years later. This application was funded in 2018 at Health Canada with Dr. JC Prior as a collaborator. Extensive negotiations by CeMCOR and HC scientists ensued about funding the process of obtaining these follow-up specimens. CeMCOR managed to obtain a HC agreement to fund the minimal cost of recruiting, training and obtaining two menstrual phase-specific urine specimens from 250 Metro Vancouver women. Because of the lack of a progesterone threshold for ovulation, we will collect one follicular and one luteal/premenstrual urine sample per woman. However, this time we will better characterize the ovulatory cycle using a validated quantitative basal temperature method5,6 that can assess luteal phase length as well as the presence/absence of evidence for ovulation. In addition we will collect serial salivary progesterone and estradiol values measured by the state-of-the-art sensitive and specific tandem mass spectrometry (LC-MS/MS) methods7 to use as the gold standard for an ovulatory cycle. There is increasing evidence that many variables differ across women’s two main menstrual cycle phases: follicular and luteal7-10. These real and potential differences in metabolism may alter the susceptibility of women to environment exposures, and also could change their urinary elimination. Those are the root reasons for doing this study.