Nine obese and ten non-obese women with polycystic ovarian disease (PCO), and seven obese and eight non-obese normal women, had an oral glucose tolerance test (OGTT) before and after treatment with GnRH agonist (buserelin 400 micrograms/day s.c. for 8 weeks) in order to investigate the effect of ovarian suppression on their insulinaemic secretion. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol (E2), androstenedione (A), testosterone (T), DHEAS, cortisol and insulin (I) were measured at time 0 of OGTT; in all samples of OGTT, E2, T, A and I were also assayed. PCO patients showed higher basal androgen levels than control patients. All subjects showed a normal glycaemic response to OGTT. The mean fasting and areas under the curve (ISA) of plasma I were significantly greater in the obese PCO women than in non-obese PCO, the normal obese and non-obese women. All PCO patients showed significantly higher fasting I and ISA values in respect to all control patients. Hyperinsulinaemic responses were 89% in PCO obese, 30% in non-obese PCO and 29% in obese control patients. After buserelin treatment, these values did not change significantly in respect to pretreatment in all groups, in spite of a significant decrease of androgen secretion. During OGTT, no variations of steroid plasma concentrations were seen in both normal or hyperinsulinaemic PCO patients. The data of this study show that hyperandrogenism, hyperinsulinism and obesity were associated with different modalities in PCO patients and that a marked decrease of androgen secretion did not restore a normal insulinaemic response to OGTT, suggesting that hyperandrogenism does not produce hyperinsulinism.
PMID 2108986 2108986 DOI 10.1093/oxfordjournals.humrep.a137058 10.1093/oxfordjournals.humrep.a137058 Lanzone et al. 1990, Lanzone 1990
Cite this article
Lanzone, A., Fulghesu, A. M., Andreani, C. L., Apa, R., Fortini, A., Caruso, A., & Mancuso, S. (1990). Insulin secretion in polycystic ovarian disease: effect of ovarian suppression by GnRH agonist. Human reproduction (Oxford, England), 5(2), 143-149. https://doi.org/10.1093/oxfordjournals.humrep.a137058
Lanzone A, Fulghesu AM, Andreani CL, Apa R, Fortini A, Caruso A, et al. Insulin secretion in polycystic ovarian disease: effect of ovarian suppression by GnRH agonist. Hum Reprod. 1990;5(2):143-149. doi:10.1093/oxfordjournals.humrep.a137058
Lanzone, Antonio, et al. "Insulin secretion in polycystic ovarian disease: effect of ovarian suppression by GnRH agonist." Human reproduction (Oxford, England), vol. 5, no. 2, 1990, pp. 143-149.
To determine whether self-selected women with polycystic ovary syndrome (PCOS) are abnormal compared with a control population. Case-control. Support group meeting organized and initiated by patients. PATIENT(S): Forty-five self-selected women with PCOS and 80 control women. INTERVENTION(S): Self-selected women with PCOS at a peer support conference completed a questionnaire, had a brief physical, and gave a fasting blood sample. MAIN OUTCOME MEASURE(S): Historical, biometric, and assay results. RESULT(S): Sixty percent of the women attending the conference participated in the study. Most had been diagnosed with PCOS on the basis of ovarian morphology (35%). They were more likely to be nulliparous and have a history of oligomenorrhea (96%). They were hyperandrogenemic (significantly elevated testosterone and DHEAS levels) compared with control women. Self-selected women with PCOS displayed multiple metabolic abnormalities compared with control women, including elevations in blood pressure, waist-hip ratio, fasting insulin, fasting total cholesterol, and fasting low-density lipoprotein cholesterol levels, as well as a significant decrease in fasting glucose-insulin ratio and high-density lipoprotein cholesterol levels. CONCLUSION(S): Self-selected women with PCOS have reproductive and metabolic abnormalities. The majority of these women received inadequate treatment despite having risk factors for endometrial cancer, diabetes, and/or heart disease. Our study also suggests that women attending or participating in a PCOS support group are willing and likely to participate in clinical studies.
To evaluate the effect of N-acetyl-cysteine (NAC) on insulin secretion and peripheral insulin resistance in subjects with polycystic ovary syndrome (PCOS). Prospective data analysis. Volunteer women in an academic research environment. PATIENT(S): Six lean and 31 obese subjects, aged 19-33 years. INTERVENTION(S): Patients were treated for 5-6 weeks with NAC at a dose of 1.8 g/day orally. A dose of 3 g/day was arbitrarily chosen for massively obese subjects. Six of 31 obese patients with PCOS were treated with placebo and served as controls. MAIN OUTCOME MEASURE(S): Before and after the treatment period, the hormonal and lipid blood profile and insulin sensitivity, assessed by an hyperinsulinemic euglycemic clamp, were evaluated and an oral glucose tolerance test (OGTT) was performed. RESULT(S): Fasting glucose, fasting insulin, and glucose area under curve (AUC) were unchanged after treatment. Insulin AUC after OGTT was significantly reduced, and the peripheral insulin sensitivity increased after NAC administration, whereas the hepatic insulin extraction was unaffected. The NAC treatment induced a significant fall in T levels and in free androgen index values (P<.05). In analyzing patients according to their insulinemic response to OGTT, normoinsulinemic subjects and placebo-treated patients did not show any modification of the above parameters, whereas a significant improvement was observed in hyperinsulinemic subjects. CONCLUSION(S): NAC may be a new treatment for the improvement of insulin circulating levels and insulin sensitivity in hyperinsulinemic patients with polycystic ovary syndrome.
Malliou-Becher MN et al., 2026·Human reproduction (Oxford, England)
What are the variations in ovulation time and menstrual cycle characteristics among and within various individuals over the course of 12 menstrual cycles? There are considerable variations in both cycle length and ovulation time, with pronounced intra-individual variability over a 12-cycle observation period. Although it is commonly believed that healthy women have regular cycles with a predictable mid-cycle ovulation, more recent research shows a significant variation in cycle length and ovulation time. Previous studies have focused only on cycle length, often excluding cycles outside the 25-35-day range, thus limiting the understanding of natural variation; they have also lacked precise ovulation diagnostics or included small sample sizes, making it difficult to capture the full scope of cycle and ovulation variability. Similarly, a recent big data study, while valuable, was limited by a self-selected group and the absence of accurate ovulation diagnostics, reducing its generalizability. STUDY DESIGN, SIZE, This study was designed as a prospective long-term observational study, which involved collecting data from 1923 women with a total of 43 999 menstrual cycles from January 1985 to July 2019. After fulfilling the inclusion criteria, the main group consisted of 1051 women, all of whom contributed data for 12 cycles (12 612 cycles), including 420 conception cycles. PARTICIPANTS/MATERIALS, SETTING, Participants in the study were between 18 and 44 years of age at study entry and did not take any reproductive hormones. Women who were postpartum, breastfeeding, amenorrheic, or within a 3-month period after stopping hormonal contraception were excluded. Participants agreed to keep cycle records according to the symptothermal method, 'Sensiplan'. Ovulation time was determined using an evidence-based algorithm based on evaluating cervical mucus patterns and basal body temperature shifts, with ovulation time defined as the day before the temperature rise. Data analysis was descriptive, using absolute and relative frequencies, standard deviation, percentiles, and ranges. Age dependency was assessed using unpaired sample t-tests and one-way ANOVA. Linear regression was used to assess long-term trends. MAIN In 62.4% of women, cycle lengths varied by 1 week or more within 12 cycles. Accordingly, the time of ovulation varied by 1 week or more within 12 cycles in 54.8% of women, with 96.5% experiencing fluctuations of 4 days or more over the 12 months. The median spontaneous cycle length was 28 days, with a mean of 29.66 days (SD = 7.55). Only 52.7% of women consistently had cycle lengths between 23 and 35 days across all 12 cycles. Ovulation occurred most frequently between Days 12 and 16, with almost half of conceptions (45.7%) occurring after Day 16. A one-way analysis of variance revealed a significant reduction in mean cycle length with increasing age (P < 0.001), showing the shortest median cycle length of 27 days being in women aged 40-44 years. Age also impacted ovulation time, with women aged 35-39 years showing more stable ovulation patterns compared to younger women. Over the 34-year study period, average cycle length increased slightly but significantly (β = 0.0161, P = 0.0306), corresponding to approximately half a day. Intra-individual variability also showed a slight, but non-significant, upward trend (β = 0.0262, P = 0.2173). LIMITATIONS, Comorbidities such as hyperprolactinemia, obesity, and PCOS were not systematically excluded. However, by including only women with at least 12 cycles, the study largely avoided severe hormonal disorders. This study highlights the considerable individual variation of ovulation time and cycle length over 12 menstrual cycles. These findings contribute to a better understanding of fertility awareness, and highlight the implications for family planning and reproductive health management. STUDY FUNDING/COMPETING INTEREST(S): The authors declare no conflicts of interest. No funding was provided. N/A.
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.