Ahrens, K., Mumford, S. L., Schliep, K. C., Kissell, K. A., Perkins, N. J., Wactawski-Wende, J., & Schisterman, E. F. (2014). Serum leptin levels and reproductive function during the menstrual cycle. American journal of obstetrics and gynecology, 210(3), 248.e1-248.e2489. https://doi.org/10.1016/j.ajog.2013.11.009
Ahrens K, Mumford SL, Schliep KC, Kissell KA, Perkins NJ, Wactawski-Wende J, et al. Serum leptin levels and reproductive function during the menstrual cycle. Am J Obstet Gynecol. 2014;210(3):248.e1-248.e2489. doi:10.1016/j.ajog.2013.11.009
Ahrens, K., et al. "Serum leptin levels and reproductive function during the menstrual cycle." American journal of obstetrics and gynecology, vol. 210, no. 3, 2014, pp. 248.e1-248.e2489.
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Eunice Kennedy Shriver National Institute of Child Health and Human Development04byxyr05
Department of Epidemiology and Environmental Health, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY.01y64my43
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Abstract
Objective
The purpose of this study was to investigate the role of leptin on reproductive hormones and ovulation.
Study Design
The BioCycle Study (2005-2007) followed 259 healthy premenopausal women not using hormonal contraceptives for ≤2 menstrual cycles (n = 509 cycles). Serum leptin, estradiol, progesterone, luteinizing hormone (LH), follicle-stimulating hormone, and testosterone were measured ≤8 times per cycle. The association of time-varying leptin and reproductive hormones over the cycle was estimated with the use of linear mixed models that were adjusted for percent body fat and age with inverse probability weighting for time-varying physical activity, caloric intake, and other reproductive hormones. The odds ratio for sporadic anovulation (n = 42 cycles) was estimated with the use of generalized linear models that were adjusted for percent body fat and age.
Results
Geometric mean serum leptin levels increased from menses to the late luteal phase (16.7-20.4 ng/mL; P < .01), with a mid-cycle peak (21.7 ng/mL) at the time of the LH surge (P < .01). A 10% higher leptin level across the menstrual cycle was associated with higher estradiol levels (2.2%; 95% CI, 1.5-3.0), luteal progesterone levels (2.1%; 95% CI, 0.5-3.7), ovulatory LH levels (1.2%; 95% CI, 0-2.3), testosterone levels (0.6%; 95% CI, 0.3-0.9), and lower follicle-stimulating hormone levels (-0.7%; 95% CI, -1.1 to -0.4). Leptin at the time of the expected LH surge was moderately inversely associated with sporadic anovulation (per log increase in leptin; adjusted odds ratio, 0.58; 95% CI, 0.28-1.22).
Conclusion
The association that was observed between leptin level and reproductive function points to a possible relationship between serum leptin level and enhanced fertility.
Schliep KC et al., 2026·J Gynecol Obstet Hum Reprod·Free full text on PubMed Central
Endometriosis has been linked to cardiometabolic alterations, but whether these associations vary by disease severity or phenotype is unclear. We examined lipid profiles across endometriosis diagnosis, stage, and typology. Data came from 476 women in the NICHD ENDO cohort. Endometriosis was confirmed laparoscopically and staged using the rASRM criteria (I-IV). Typology was categorized as superficial endometriosis (SE), ovarian endometrioma (OE), deep infiltrating endometriosis (DE), and OE+DE. We compared endometriosis status, stage (I/II vs III/IV), and typology to no endometriosis using adverse lipid thresholds (total cholesterol ≥200 mg/dL, HDL <50 mg/dL, LDL ≥100 mg/dL, triglycerides ≥175 mg/dL, non-HDL ≥130 mg/dL, VLDL ≥30 mg/dL, ApoA1 <125 mg/dL, and ApoB ≥120 mg/dL). Adjusted prevalence ratios (aPR) and 95 % CIs were estimated via generalized linear models, controlling for age, race/ethnicity, BMI, income, marital status, and serum cotinine. Endometriosis diagnosis alone was not associated with adverse lipid profiles. In contrast, moderate/severe disease showed higher prevalence of elevated triglycerides (aPR= 2.27; 95 % CI: 1.18,4.35) and VLDL (aPR= 2.41; 95 % CI: 1.50, 3.85). Typology revealed stronger patterns: OE and OE+DE were associated with adverse profiles across multiple markers (aPRs 1.59-4.09), particularly ApoB and triglycerides. Minimal/mild disease and SE were not associated. The metabolic signal was phenotype-driven rather than diagnosis-driven, with severe stage and OE/OE+DE showing clear associations with adverse lipid profiles. These findings suggest lipid profiles may serve as markers of phenotype severity or shared biological milieu. Replication in larger cohorts is needed.
Reeder MR et al., 2026·Fertil Steril·Free full text on PubMed Central
To examine birth outcomes between children conceived with in vitro fertilization (IVF) or intrauterine insemination (IUI) and sibling births from unassisted conceptions. Retrospective sibling cohort. Live born children conceived via IVF, with or without intracytoplasmic sperm injection, or IUI at the Utah Center for Reproductive Medicine, 1999-2018, and sibling births from unassisted conceptions (born 1985-2018). The main analysis included singleton births (460 IVF, 666 IUI, and 1,579 unassisted siblings). Exposure: In vitro fertilization, with or without intracytoplasmic sperm injection, or IUI. Preterm birth, low birth weight, small for gestational age, large for gestational age (LGA), and major congenital anomalies. Compared with unassisted siblings, singleton children conceived via IVF had gestational ages shorter by nearly half a week (95% confidence interval [CI], -0.6 to -0.3), birth weights of 72.1 g lower (95% CI, -118.8 to -25.4), and higher proportions of preterm birth (IVF, 11.1%; IUI, 8.7%; unassisted siblings, 6.8%), LGA (IVF, 9.1%; IUI, 4.5%; unassisted siblings, 5.9%), and major congenital anomalies (IVF, 3.7%; IUI, 2.0%; unassisted siblings, 1.4%). Models adjusted for maternal age, infant sex, infant birth year, previous pregnancy, and birth order showed that children conceived via IVF were more likely to be preterm (adjusted risk ratio [aRR], 1.6; 95% CI, 1.2-2.2; absolute difference, 4.3%) and LGA (aRR, 1.8; 95% CI, 1.2-2.5; absolute difference, 3.2%). Children conceived via IVF had a higher risk of major congenital anomalies than unassisted siblings adjusted for maternal age, infant sex, and birth order (aRR, 1.9; 95% CI, 1.0-3.8; absolute difference, 2.3%). Children conceived via IUI had birth weights 55.8 g lower (95% CI, -95.6 to -15.9) than unassisted siblings. We observed an increased risk of preterm birth, low birth weight, LGA, and major congenital anomalies among singleton children conceived with IVF compared with that among unassisted siblings; however, absolute differences remain small. For children conceived via IUI, lower birth weights were observed. These results suggest that treatment-related factors in addition to underlying subfertility may contribute to adverse birth outcomes.
Valenti M et al., 2026·Am J Obstet Gynecol·Free full text on PubMed Central
Endometriosis is a chronic, gynecologic condition in which tissue similar to the lining of the uterus implants throughout the body. Women with endometriosis have a higher prevalence of infertility and a greater risk of early natural menopause compared to those without endometriosis. This study aimed to evaluate preoperative serum AMH levels among women with and without incident endometriosis and to assess whether levels differ by surgical staging and typology. The ENDO (Endometriosis: Natural History, Diagnosis, and Outcomes) study was conducted between 2007 and 2009. The ENDO study consisted of an operative and population cohort (n=600). Only those in the ENDO operative cohort from the Utah site were used for this analysis, and included women aged 18 to 44 years who were scheduled for gynecologic surgery, irrespective of clinical indication (n=476). AMH levels were measured from stored serum collected before surgery using a quantitative enzyme-linked immunosorbent assay. After excluding participants with missing outcome data (n=51), unilateral oophorectomy (n=8), or those within the population cohort (n=69), 348 participants remained for the analysis. Surgically confirmed endometriosis diagnosis, staging (American Society for Reproductive Medicine I-IV), and typology (superficial, deep, ovarian) were ascertained by the operative report. Outliers for AMH (>14.0 ng/mL) were excluded from the analyses and AMH values were log-transformed. Multivariable linear regression models adjusted for age (squared and continuous), body mass index, serum cotinine levels, and exogenous hormonal contraceptive use were conducted. Percentage differences in AMH were calculated as (exp[β]-1)×100, and 95% confidence intervals were reported. Compared with no endometriosis, incident endometriosis diagnosis was associated with lower AMH levels (-19.8%; 95% confidence interval, -37.0 to 1.0); however, this association was not statistically significant. Stage III to IV disease was associated with 40.1% lower AMH levels (95% confidence interval, -58.9 to -12.7). Ovarian endometriomas were most strongly associated with lower AMH levels (-54.3%; 95% confidence interval, -69.4 to -31.8), with a more pronounced association among those with infertility (-72.6%; 95% confidence interval, -85.4 to -48.5). Deep (-24.1%; 95% confidence interval, -48.2 to 11.0) and superficial (-15.5%; 95% confidence interval, -34.6 to 9.3) endometriosis also showed a trend toward lower AMH levels, but these findings were not statistically significant. Compared with a postoperative diagnosis of a normal pelvis, incident endometriosis was associated with 26.8% lower AMH levels (95% confidence interval, -44.6 to -3.4). Stage III to IV disease was associated with 47.8% lower AMH levels (95% confidence interval, -65.8 to -23.2), and all subtypes of endometriosis were statistically significantly associated with lower levels of AMH compared with a postoperative diagnosis of a normal pelvis (ovarian: -60.8%; 95% confidence interval, -74.4 to -39.9; deep: -34.3%; 95% confidence interval, -56.2 to -1.4; superficial: -24.8%; 95% confidence interval, -43.9 to -0.8). Ovarian and moderate to severe (stage III-IV) endometriosis were associated with markedly lower AMH levels compared with no endometriosis. Compared with a postoperative diagnosis of a normal pelvis, incident endometriosis and moderate to severe stages (stage III-IV) were associated with statistically significantly lower AMH levels. Additionally, typology (deep, ovarian, or superficial) was associated with statistically significantly lower AMH levels. However, this association was likely driven by the presence of ovarian endometriomas across all subtypes. These findings are consistent with previous studies and demonstrate that endometriosis lesions themselves, independent of surgical intervention, influence AMH levels.
Fertility and Outcomes · Conception After Excision
Hsu JZ et al., 2025·Eur J Obstet Gynecol Reprod Biol
Endometriosis is a chronic gynaecological condition affecting reproductive-aged women. It has been associated with infertility and potential risks for adverse pregnancy outcomes, although population-level evidence remains limited. This retrospective cohort study, including 147,950 pregnant women aged 20-45 years, used nationwide population-based data to compare the outcomes between women with (n = 11,400) and without (n = 136,550) endometriosis between 2000 and 2021. Baseline characteristics, comorbidities and pregnancy outcomes were compared between the groups. Multivariable regression analyses were performed to calculate adjusted relative risks (aRR) and 95 % confidence intervals (CI) for various pregnancy outcomes, and subgroup analyses were conducted by maternal age and infertility status. Among 147,950 pregnancies, women with endometriosis [mean ± standard deviation (SD) age 32.38 ± 4.51 years] had higher socio-economic status, more comorbidities, and more surgical history compared with women without endometriosis (mean ± SD age 30.06 ± 4.96 years). Women with endometriosis had increased risk of miscarriage (aRR 1.13, 95 % CI 1.03-1.24), preterm birth (aRR 1.31, 95 % CI 1.26-1.37), premature rupture of membranes (aRR 1.11, 95 % CI 1.06-1.16), placenta previa (aRR 1.63, 95 % CI 1.45-1.84), urinary tract infection (aRR 1.44, 95 % CI 1.31-1.59), and caesarean section (aRR 1.13, 95 % CI 1.11-1.16). Subgroup analysis revealed that risk of miscarriage was only higher in women aged 35-45 years and women without infertility. Risks of preterm birth, placenta previa and caesarean section were elevated across all subgroups, suggesting that endometriosis contributes independently to adverse pregnancy outcomes. Endometriosis is an independent risk factor for several pregnancy complications, supporting the need for tailored prenatal care and closer monitoring of affected women to improve maternal outcomes.
Prasad A et al., 2014·Horm Behav·Free full text on PubMed Central
We investigated whether sexual activity was associated with reproductive function in the BioCycle Study, a prospective cohort study that followed 259 regularly menstruating women aged 18 to 44years for one (n=9) or two (n=250) menstrual cycles in 2005-2007. Women were not attempting pregnancy nor using hormonal contraceptives. History of ever having been sexually active was assessed at baseline and frequency of sexual activity, defined as vaginal-penile intercourse, was self-reported daily throughout the study. Serum concentrations of estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone, and testosterone were measured up to 8times/cycle. Sporadic anovulation was identified using peak progesterone concentration. Linear mixed models were used to estimate associations between sexual activity and reproductive hormone concentrations and generalized linear models were used to estimate associations with sporadic anovulation. Models were adjusted for age, race, body mass index, perceived stress, and alcohol consumption and accounted for repeated measures within women. Elevated concentrations of estrogen (+14.6%, P<.01), luteal progesterone (+41.0%, P<.01) and mid-cycle LH (+23.4%, P<.01), but not FSH (P=.33) or testosterone (P=.37), were observed in sexually active women compared with sexually inactive women (no prior and no study-period sexual activity); sexually active women had lower odds of sporadic anovulation (adjusted odds ratio=0.34, 95% confidence interval: 0.16-0.73). Among sexually active women, frequency of sexual activity was not associated with hormones or sporadic anovulation (all P>.23). Findings from our study suggest that ever having been sexually active is associated with improved reproductive function, even after controlling for factors such as age.
To characterize the relationships between body mass index (BMI) and LH or FSH levels over the cycle in normally cycling women. We compared baseline characteristics, cycle characteristics, follicle sizes, and daily hormone levels among women with low (n = 22), normal (n = 63), or high (n = 22) BMIs over 326 cycles. There were no significant differences in age or other lifestyle characteristics between groups. High BMI was significantly associated with younger age at menarche and less sleeping time. No differences were observed between high- and low-BMI groups in cycle length or diameter of the dominant follicle. Luteinizing hormone levels were significantly higher only in the beginning of the cycle in women with low BMIs than in those with high BMIs. Follicle-stimulating hormone levels were also significantly higher but were high during all three phases of the cycle (early follicular, periovulatory, and luteal phases). Mean levels were approximately 1. 9, 1.8, and 1.2 times higher, respectively, in the low-BMI group than the high-BMI group. Luteinizing hormone levels and BMI were inversely associated in normally cycling women during the early follicular phase. Follicule-stimulating hormone levels and BMI were inversely associated during the whole cycle, independent of age.
Schliep KC et al., 2015·Am J Clin Nutr·Free full text on PubMed Central
Although habitual low-to-moderate alcohol intake has been linked with reduced all-cause mortality and morbidity, the effect of recent alcohol intake on female reproductive function has not been clearly established. We assessed the relation between acute alcohol consumption, reproductive hormones, and markers of menstrual cycle dysfunction including sporadic anovulation, irregular cycle length, luteal phase deficiency, long menses, and heavy blood loss.
A total of 259 healthy, premenopausal women from Western New York were followed for ≤2 menstrual cycles (2005-2007) and provided fasting blood specimens during ≤8 visits/cycle and four 24-h dietary recalls/cycle. Linear mixed models were used to estimate associations between previous day's alcohol intake and hormone concentrations, whereas Poisson regression was used to assess RR of cycle-average alcohol intake and menstrual cycle function. For every alcoholic drink consumed, the geometric mean total and free estradiol, total and free testosterone, and luteinizing hormone were higher by 5.26% (95% CI: 1.27%, 9.41%), 5.82% (95% CI: 1.81%, 9.99%), 1.56% (95% CI: 0.23%, 2.90%), 1.42% (95% CI: 0.02%, 2.84%), and 6.18% (95% CI: 2.02%, 10.52%), respectively, after adjustment for age, race, percentage of body fat, perceived stress, pain-medication use, sexual activity, caffeine, and sleep. Binge compared with nonbinge drinking (defined as reporting ≥4 compared with <4 drinks/d, respectively) was associated with 64.35% (95% CI: 18.09%, 128.71%) and 63.53% (95% CI: 17.41%, 127.73%) higher total and free estradiol. No statistically significant associations were shown between cycle-average alcohol intake and menstrual cycle function. Although recent moderate alcohol intake does not appear to have adverse short-term effects on menstrual cycle function, including sporadic anovulation, potential protective and deleterious long-term effects of alterations in reproductive hormones on other chronic diseases warrant additional investigation.
The irregular menses experienced by obese and/or hirsute women were studied by daily measurement of serum LH, FSH, estradiol (E2) and progesterone (P). During 8 cycles of 24 to 157 days, each episode of menstrual bleeding was preceded by hormonal evidence of follicular maturation and corpus luteum formation. The premenstrual fluctuations of LH and E2 were not different from those observed in normal cycles. Although the luteal phase was of more than 10 days' duration, progesterone secretion was subnormal during each cycle. Serum FSH was low throughout the time preceding the LH/FSH surge. These data suggest that inadequate corpus luteum progesterone secretion may be characteristic of the menstrual cycles in oligomenorrheic, obese infertile women.
Sunni L Mumford, Karen C Schliep, Neil J Perkins, Enrique F Schisterman, Jean Wactawski-Wende
S Mumford, K Schliep, N Perkins, E Schisterman, J Wactawski-Wende
PMID 24215851 24215851 DOI 10.1016/j.ajog.2013.11.009 10.1016/j.ajog.2013.11.009 Ahrens et al. 2014, Ahrens 2014
Cite this article
Ahrens, K., Mumford, S. L., Schliep, K. C., Kissell, K. A., Perkins, N. J., Wactawski-Wende, J., & Schisterman, E. F. (2014). Serum leptin levels and reproductive function during the menstrual cycle. American journal of obstetrics and gynecology, 210(3), 248.e1-248.e2489. https://doi.org/10.1016/j.ajog.2013.11.009
Ahrens K, Mumford SL, Schliep KC, Kissell KA, Perkins NJ, Wactawski-Wende J, et al. Serum leptin levels and reproductive function during the menstrual cycle. Am J Obstet Gynecol. 2014;210(3):248.e1-248.e2489. doi:10.1016/j.ajog.2013.11.009
Ahrens, K., et al. "Serum leptin levels and reproductive function during the menstrual cycle." American journal of obstetrics and gynecology, vol. 210, no. 3, 2014, pp. 248.e1-248.e2489.
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