Association between endometriosis and type and age of menopause: a pooled analysis of 279 948 women from five cohort studies

Dietary patterns and age at menarche in a prospective study of girls in the USA

Davis CP et al., 2025·Hum Reprod

Are dietary patterns associated with age at menarche after accounting for BMI-for-age (BMIz) and height? We observed associations between both the Alternative Healthy Eating Index (AHEI) and the Empirical Dietary Inflammatory Pattern (EDIP) and age at menarche. Dietary patterns have been sparsely examined in relation to age at menarche and no studies have examined the association between the AHEI, a healthier diet, and EDIP, a pro-inflammatory diet, and menarche. STUDY DESIGN, SIZE, The Growing Up Today Study (GUTS) is a prospective cohort of children ages 9-14 years at study enrollment. GUTS enrolled in two waves with enrollment beginning in 1996 (GUTS1) and 2004 (GUTS2). For this analysis, GUTS1 and GUTS2 participants were followed through 2001 and 2008, respectively. PARTICIPANTS/MATERIALS, SETTING, We included 7530 participants who completed food frequency questionnaire(s) (FFQ) prior to menarche who then self-reported age at menarche during study follow-up. Cox proportional hazard models were used to calculate multivariable hazard ratios (HRs) and 95% CIs for the associations between two dietary patterns, the AHEI and EDIP, and age at menarche, with and without adjustment for time-varying BMIz and height. MAIN Six thousand nine hundred ninety-two participants (93%) reported menarche during the study period. On average, participants completed the baseline FFQ 1.75 years prior to menarche. Participants in the highest quintile of AHEI diet score (indicating a healthier diet) were 8% less likely to attain menarche within the next month compared to those in the lowest quintile (95% CI = 0.85-0.99; Ptrend = 0.03). This association remained after adjustment for BMIz and height (corresponding HR = 0.93; 95% CI = 0.86-1.00; Ptrend = 0.04). Participants in the highest quintile of the EDIP score (i.e. most inflammatory diet), were 15% more likely to attain menarche in the next month relative to those in the lowest quintile (95% CI = 1.06-1.25; Ptrend = 0.0004), and the association remained following adjustment for BMIz and height (corresponding HR = 1.15; 95% CI = 1.06-1.25; Ptrend = 0.0004). LIMITATIONS, Self-reported questionnaires are subject to some error; however, given our prospective study design it is likely this error is non-differential with respect to the outcome. Our findings of an association between both the AHEI and EDIP and age at menarche indicate that diet quality may play a role in age at menarche independent of BMI or height. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Breast Cancer Research Foundation. The GUTS is supported by the National Institutes of Health U01 HL145386. C.P.D. was supported by National Institutes of Health T32 CA094880. The authors have no conflicts of interest to disclose. N/A.

Spermatozoa as harbingers of mortality: the curious link between semen quality and life expectancy

Aitken RJ, 2025·Human reproduction (Oxford, England)

Validation of administrative health data for the identification of endometriosis diagnosis

Kiser AC et al., 2024·Hum Reprod

How do endometriosis diagnoses and subtypes reported in administrative health data compare with surgically confirmed disease? For endometriosis diagnosis, we observed substantial agreement and high sensitivity and specificity between administrative health data-International Classification of Diseases (ICD) 9 codes-and surgically confirmed diagnoses among participants who underwent gynecologic laparoscopy or laparotomy. Several studies have assessed the validity of self-reported endometriosis in comparison to medical record reporting, finding strong confirmation. We previously reported high interand intra-surgeon agreement for endometriosis diagnosis in the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) Study. STUDY DESIGN, SIZE, In this validation study, participants (n = 412) of the Utah operative cohort of the ENDO Study (2007-2009) were linked to medical records from the Utah Population Database (UPDB) to compare endometriosis diagnoses from each source. The UPDB is a unique database containing linked data on over 11 million individuals, including statewide ambulatory and inpatient records, state vital records, and University of Utah Health and Intermountain Healthcare electronic healthcare records, capturing most Utah residents. PARTICIPANTS/MATERIALS, SETTING, The ENDO operative cohort consisted of individuals aged 18-44 years with no prior endometriosis diagnosis who underwent gynecologic laparoscopy or laparotomy for a variety of surgical indications. In total, 173 women were diagnosed with endometriosis based on surgical visualization of disease, 35% with superficial endometriosis, 9% with ovarian endometriomas, and 14% with deep infiltrating endometriosis. Contemporary administrative health data from the UPDB included ICD diagnostic codes from Utah Department of Health in-patient and ambulatory surgery records and University of Utah and Intermountain Health electronic health records. MAIN For endometriosis diagnosis, we found relatively high sensitivity (0.88) and specificity (0.87) and substantial agreement (Kappa [Κ] = 0.74). We found similarly high sensitivity, specificity, and agreement for superficial endometriosis (n = 143, 0.86, 0.83, Κ = 0.65) and ovarian endometriomas (n = 38, 0.82, 0.92, Κ = 0.58). However, deep infiltrating endometriosis (n = 58) had lower sensitivity (0.12) and agreement (Κ = 0.17), with high specificity (0.99). LIMITATIONS, Medication prescription data and unstructured data, such as clinical notes, were not included in the UPDB data used for this study. These additional data types could aid in detection of endometriosis. Most participants were white or Asian with Hispanic ethnicity reported 11% of the time, which may limit generalizability to some US states. Additionally, given that participants whose administrative health records we utilized were also part of the ENDO Study, the surgeons may have been more vigilant in diagnostic coding due to the operative forms they completed for the ENDO Study, which may have led to increased validity. However, the codes compared in the UPDB would have been entered by medical coders as part of standard clinical practice. We observed substantial agreement between administrative health data and surgically confirmed endometriosis diagnoses overall, and for superficial and ovarian endometrioma subtypes. These findings may provide reassurance to researchers using administrative healthcare records to assess risk factors and long-term health outcomes of endometriosis. Our findings corroborate prior research that demonstrates high specificity but low sensitivity for deep infiltrating endometriosis, indicating deep infiltrating endometriosis is not reliably annotated in administrative healthcare data. This suggests that medical record-based deep infiltrating endometriosis diagnoses may be suitable for etiologic studies but not for surveillance or detection studies. STUDY FUNDING/COMPETING INTEREST(S): The original ENDO Study was funded by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contracts NO1-DK-6-3428; NO1-DK-6-3427; 10001406-02). We acknowledge partial support for the UPDB through grant P30 CA2014 from the National Cancer Institute, University of Utah and from the University of Utah's program in Personalized Health and Center for Clinical and Translational Science. This research was also supported by the NCRR grant, 'Sharing Statewide Health Data for Genetic Research' (R01 RR021746, G. Mineau, PI) with additional support from the Utah Department of Health and Human Services, University of Utah. Additionally, this research was supported by the Utah Cancer Registry, which is funded by the National Cancer Institute's SEER Program, Contract No. HHSN261201800016I, the US Centers for Disease Control and Prevention's National Program of Cancer Registries, Cooperative Agreement No. NU58DP007131, with additional support from the University of Utah and Huntsman Cancer Foundation. Research reported in this publication was also supported by the National Institutes of Health (Award Numbers R01HL164715 [to L.V.F., K.C.S., and A.Z.P.] and K01AG058781 [to K.C.S.]), by the Huntsman Cancer Institute's Breast and Gynecologic Cancers Center, and by the Doris Duke Foundation's COVID-19 Fund to Retain Clinical Scientists funded by the American Heart Association. A.C.K. was supported by Training Grant Number 5T15LM007124 from the National Library of Medicine to K.E. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other sponsors. There are no competing interests among any of the authors. N/A.

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

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, 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 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.