Adolescent combined hormonal contraceptives and surgical repair of anterior cruciate tears: a risky recommendation based on an unproven causal relationship

The influence of the menstrual cycle on muscle injuries - a systematic review and meta-analysis

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.

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 · Free full text on PubMed Central

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.

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 · Free full text on PubMed Central

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.

"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., 2025 · J Endocr Soc · Free full text on PubMed Central

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, and AMH each decreased: 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.

Combined hormonal contraceptive use is not protective against musculoskeletal conditions or injuries: a systematic review with data from 5 million females

White L et al., 2023 · Br J Sports Med

Assess the association between combined hormonal contraceptives (CHC) use and musculoskeletal tissue pathophysiology, injuries or conditions. Systematic review with semiquantitative analyses and certainty of evidence assessment, guided by the Grading of Recommendations Assessment, Development and Evaluation approach. Data Sources: MEDLINE, EMBASE, CENTRAL, SPORTDiscus, CINAHL searched from inception to April 2022. Intervention and cohort studies that assessed the association between new or ongoing use of CHC and an outcome of musculoskeletal tissue pathophysiology, injury or condition in postpubertal premenopausal females. Across 50 included studies, we assessed the effect of CHC use on 30 unique musculoskeletal outcomes (75% bone related). Serious risk of bias was judged present in 82% of studies, with 52% adequately adjusting for confounding. Meta-analyses were not possible due to poor outcome reporting, and heterogeneity in estimate statistics and comparison conditions. Based on semiquantitative synthesis, there is low certainty evidence that CHC use was associated with elevated future fracture risk (risk ratio 1.02-1.20) and total knee arthroplasty (risk ratio 1.00-1.36). There is very low certainty evidence of unclear relationships between CHC use and a wide range of bone turnover and bone health outcomes. Evidence about the effect of CHC use on musculoskeletal tissues beyond bone, and the influence of CHC use in adolescence versus adulthood, is limited. Given a paucity of high certainty evidence that CHC use is protective against musculoskeletal pathophysiology, injury or conditions, it is premature and inappropriate to advocate, or prescribe CHC for these purposes. This review was registered on PROSPERO CRD42021224582 on 8 January 2021.

The Effect of Menstrual Cycle and Contraceptives on ACL Injuries and Laxity: A Systematic Review and Meta-analysis

Herzberg SD et al., 2017 · Orthopaedic journal of sports medicine · Free full text on PubMed Central

Women are at substantially greater risk for anterior cruciate ligament (ACL) injuries than are men. To conduct a systematic review and meta-analysis of the literature to clarify the effect of the menstrual cycle and contraceptives on the laxity of and noncontact injuries to the ACL. Systematic review; Level of evidence, 4. Searches were conducted using MEDLINE (1946-August 2016), the Cochrane Library Database, clinical trial registries, and related reference lists. Search terms included athletic injuries, knee injuries, ligaments, joint instability, menstrual cycle, ovulation, hormones, and contraceptives. Investigators independently dually abstracted and reviewed study details and quality using predefined criteria and evaluated overall strength of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. Twenty-one studies totaling 68,758 participants were included: 5 on the menstrual cycle and ACL injury, 7 on hormonal contraceptives and ACL injury, as well as 13 on menstrual cycle and ligament laxity. Four of 5 studies of women not using hormonal contraception indicated that the luteal phase was the least associated with ACL injuries. The 2 largest and highest quality studies on hormonal contraceptives suggested that hormonal contraceptives may be protective against ACL injury. Six of 12 studies on ACL laxity provided quantitative data for meta-analysis, finding significantly increased laxity during the ovulatory phase compared with the follicular phase. The literature suggests an association between hormonal fluctuations and ACL injury. Recent studies have suggested that oral contraceptives may offer up to a 20% reduction in risk of injury. The literature on ACL injuries and the menstrual cycle has more than doubled over the past decade, permitting quantitative analysis for the first time. However, the overall strength of this evidence is low. Promising potential directions for future research include long-term observational studies with ongoing hormonal assays and large interventional trials of follicular suppression, including newer hormonal methods.

Adolescent use of combined hormonal contraception and peak bone mineral density accrual: A meta-analysis of international prospective controlled studies

Goshtasebi A et al., 2019 · Clin Endocrinol (Oxf) · Free full text on PubMed Central

Many women use combined hormonal contraceptives (CHC) during adolescence during which they are accruing peak areal bone mineral density (BMD) that relates to lifetime fracture risk. To build BMD requires formation with which CHC-related exogenous oestrogen may interfere. We compared peak BMD accrual in adolescents using and not using CHC. We performed literature searches for prospective published peer-reviewed articles providing 12to 24-month BMD change in adolescent (12to 19-year-old) women using CHC vs CHC-unexposed control women. Meta-analyses used random-effects models to assess BMD change rate at lumbar spine (LS) and other sites in adolescent CHC users vs CHC nonusers. Literature searches yielded 84 publications of which nine were eligible. Adolescent-only data were sought from cohorts with wider age inclusions. The 12-month LS meta-analysis with eight paired comparisons in 1535 adolescents showed a weighted mean BMD difference of -0.02 (95% confidence interval [CI]: -0.05 to 0.00) g/cm(2) in CHC-exposed adolescents (P = 0.04). The 24-month LS meta-analysis with five paired comparisons in 885 adolescents showed a highly significant weighted mean BMD difference of -0.02 (95% CI: -0.03 to -0.01) g/cm(2) in CHC-exposed adolescents (P = 0.0006). Heterogeneities by I(2) were 96% and 85%, respectively. Insufficient data for other bone sites precluded quantitative analysis. Given that adolescent exposure to CHC appears to be increasing, this evidence for potential impairment of peak spinal BMD accrual is of concern and suggests a potential public health problem. Randomized controlled trial data are needed to determine CHC effects on adolescent bone health.

HOW CAN WE PROTECT PEAK BONE MASS AND FUTURE BONE HEALTH FOR ADOLESCENT WOMEN? - BY SUPPORTING OVULATION AND AVOIDING COMBINED HORMONAL CONTRACEPTION USE

Prior JC, 2017 · Rev Paul Pediatr · Free full text on PubMed Central