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, Shirin S, Bos C, Kalidasan D, Prior JC

doi:10.1210/jendso/bvaf149.1891

Journal of the Endocrine Society, 9(Supplement_1), 2025

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

Alexandra Baaske , Constance Bos , Dharani Kalidasan

Author affiliations (2)

University of British Columbia ROR
Vancouver Hospital and Health Sciences Centre ROR

DOI10.1210/jendso/bvaf149.1891

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Abstract

Disclosure: A.V. Baaske: None. S. Shirin: None. C. Bos: None. D. Kalidasan: None. J.C. Prior: None.

Background

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.

Objective

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.

Methods

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.

Results

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.

Conclusions

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

Topics

Menstrual Cycle > Ovulation > Ovulatory Disturbances Menstrual Cycle > Physiology > Breast Changes Reproductive Endocrinology > Progesterone > Physical Markers

breast areolar diameter ovulatory status premenopausal women, Prior JC areolar diameter progesterone menstrual cycle, Tanner breast stage ovulation progesterone exposure, quantitative basal temperature QBT ovulation analysis, areolar diameter body mass index BMI association, breast development markers ovulatory disturbances, menstrual cycle diary breast physical examination cross-sectional, bilateral areolar measurement body size reproductive variables, age at menarche areolar diameter relationship, subclinical ovulatory disturbance short luteal phase anovulation detection

DOI 10.1210/jendso/bvaf149.1891 10.1210/jendso/bvaf149.1891

Cite this article

Baaske, A. V., Shirin, S., Bos, C., Kalidasan, D., & Prior, J. C. (2025). MON-154 Breast areolar diameter in healthy menstruating women—a single cycle cross-sectional study of associations with body size and ovulatory characteristics. Journal of the Endocrine Society, 9(Supplement_1). https://doi.org/10.1210/jendso/bvaf149.1891

Menstrual CycleSubclinical Ovulatory DisturbancesPremenstrual Breast ChangesSymptom Documentation Open Access

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., 2025Journal of the Endocrine Society

M. None. J.C. None. S. None. A. 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. Saturday, July 12, 2025

PCOSProgesterone TherapyAntiandrogen TherapyPatient-Reported Outcomes Open Access

"SUN-109 Feasibility of Cyclic Progesterone and Spironolactone for PCOS-specific Health-Related Quality of Life—a six-month, Phase II, single arm, single center, open-label study"

Nelson K et al., 2025J Endocr Soc

K. None. J. None. A. None. D. None. J. None. Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder that significantly decreases health-related quality of life (HRQoL). Combined hormonal contraceptives (CHC) are standard-of-care for PCOS but do not mitigate the neuroendocrine cause nor women’s primary concerns. Treatment options need expansion. We hypothesized cyclic oral micronized progesterone (CyclicP4) and spironolactone (Sp) would improve HRQoL, decrease LH, and acne. This Phase II, open-label single-arm pilot study evaluated the 6-month cyclicP4 and Sp treatment feasibility and safety in androgenic PCOS. Our primary outcome was within-woman change in PCOS-HRQoL (PCOSQ). No sample size calculation was possible; 40 was considered feasible. Eligible women were 19-40 years with physician-diagnosed androgenic PCOS. Exclusion criteria included HbA1c > 6.4%, use of metformin or CHC in the last month. Participants received progesterone (300 mg/bedtime 14 days/month); spironolactone (200 mg/day) began in cycle two. Adherence was tracked daily (Menstrual Cycle Diary©) and by pill counts. Safety was assessed by post-study potassium (K+). Feasibility by women’s post-trial treatment intention. PCOSQ, serum LH, calculated bioavailable testosterone (cBAT), HbA1c, hsCRP, and AMH were measured at baseline and trial end. We also assessed perceived acne and sleep changes (-5 to +5), K+ and therapy intent at study end. Six-month change by paired t-test or Wilcoxon signed-rank assessed P < .05 as important. Of 109 expressing interest, 41 enrolled, 36 began therapy (5 did not), and 26 provided final questionnaire data (19 with complete lab data). Completing women were mean age 29 (SD 4.9) years, BMI 30.3 (8.1), 61.5% White and 73.1% with university degrees. Total PCOSQ scores within-woman increased from 3.5±1.0 to 4.9±1.1 (95% CI 3.1-3.8, 4.6-5.3; P<.0000001). Each PCOSQ domain significantly improved (at least P<.001) as did acne and sleep. Weight was unchanged but waist circumference decreased 1.1 cm (NS). LH, cBAT, LH 10.0±5.4 to 8.5±5.2 IU/L (95% CI 7.6-12.3, 6.3-10.8; P<.4), cBAT 0.7±0.4 to 0.6±0.3 nmol/L (0.5-0.9, 0.5-0.8; P<.2), and AMH 10.5±6.5 to 9.7±5.7 ng/ml (7.4-13.7, 7.0-12.4; P<.4). hsCRP remained unchanged (2.8±3.3 to 2.7±3.6 mg/L; P<.8) as did HbA1c (5.2±0.3 to 5.2±0.3%; P<.0). K+ remained within the normal range (3.5-5.0 mmol/L) at final testing (mean 4.0). Two allergic responses to spironolactone and one frequent flow/religious practice led to discontinuation. Feasibility was confirmed and participants strongly preferred continuing therapy (median Likert score=6/7, P<.0001) CyclicP4 and Sp for 6-months was feasible and significantly improved HRQoL in a non-medicine-seeking community women cohort with androgenic PCOS. Though the small sample size limited generalizability, findings are promising. A larger randomized trial comparing CyclicP4 vs. CHC is warranted. Sunday, July 13, 2025

PCOSCyclic Progesterone TherapyLuteal Phase ReplacementOligomenorrhea Management Open Access

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

Shirin S et al., 2020J Endocr Soc

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 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 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. 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 //hellocluecom/articles/cycle-a-z/the-case-for-a-new-pcos-therapy 2018

PCOSCyclic Progesterone TherapyLiterature SearchNeuroendocrine Mechanisms Open Access

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

Shirin S et al., 2020J Endocr Soc

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. 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. “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. 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.

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

Abstract

Topics

Cite this article

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