Laura Zanotti

The effect of dietary soy supplementation on hot flushes.

Objective To study infectious pathology at index ectopic pregnancy and to determine what other factors predispose a woman to repeat ectopic pregnancy. Methods All women (n = 697) with their first (index) ectopic pregnancy histologically verified between January 1, 1978, and December 31, 1993, at the only two hospitals in one Norwegian county were eligible. Included were permanent residents of the county who were 37 years of age or younger and who had not had tubal surgery before the index pregnancy. When the study closed on November 1, 1994, the participants had been observed prospectively for fertility events from approximately 1 to 17 years. Included in the final analyses were 353 women who had from one to five natural conceptions, for a total of 555 pregnancies. Chisquare test was used in univariate analysis, and the generalized estimating equations approach was used to analyze correlated responses and covariates that changed over time. Results Pregnancy order is the stronger correlate of subsequent ectopic pregnancy. The frequency of repeat ectopic pregnancy decreased by one-third for each pregnancy from the first to the third pregnancy. The odds of having another ectopic pregnancy were nearly three times higher for women with a diagnosis of infectious pathology than for women who had no infectious pathology. Other correlates of repeat ectopic pregnancy include age 24 years or younger at first ectopic pregnancy, history of repeat ectopic pregnancy, initiation of infertility work-up, and conception with an intra-uterine device at index pregnancy. Method of surgery was not associated with repeat ectopic pregnancy. Conclusion The most crucial reproductive event after first ectopic pregnancy is the first event to occur. Women who have experienced two ectopic pregnancies should be considered candidates for assisted reproduction.

Androgen Profiling by Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) in Healthy Normal-Weight Ovulatory and Anovulatory Late Adolescent and Young Women

CONTEXT Physiological transient imbalance typical of adolescence needs to be distinguished from hyperandrogenism-related dysfunction. The accurate determination of circulating androgens is the best indicator of hyperandrogenism. However, reliable reference intervals for adolescent and young women are not available. OBJECTIVE The aim of the study was to define androgen reference intervals in young women and to analyze the impact of the menstrual phase and ovulation efficiency over the androgen profile as assessed by reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique. PARTICIPANTS Female high school students aged 16-19 years were included in the study. MAIN OUTCOME MEASURES The study was performed on reference subjects properly selected among an unbiased population. Normal-weight, drug and disease free, eumenorrheic females with no signs of hyperandrogenism were included. The steroid hormone profile was determined by a validated in-house LC-MS/MS method. A statistical estimation of overall and menstrual phase-specific reference intervals was performed. A subgroup of anovulatory females was identified based on progesterone circulating levels. The impact of ovulation efficiency over hormonal profile was analyzed. RESULTS A total of 159 females satisfied healthy criteria. Androgen levels did not vary according to menstrual phase, but a significantly higher upper reference limit was found for T in the luteal phase compared to the follicular phase. Higher T and androstenedione levels were observed in anovulatory compared to ovulatory females, paralleled by higher LH and FSH and lower 17-hydroxyprogesterone and 17β-estradiol levels. CONCLUSIONS This is the first study providing LC-MS/MS-based, menstrual phase-specific reference intervals for the circulating androgen profile in young females. We identified a subgroup of anovulatory healthy females characterized by androgen imbalance.

Prevalence of hyperandrogenic states in late adolescent and young women: epidemiological survey on italian high-school students.

CONTEXT Most of the estimates of the prevalence of hyperandrogenic states refer to the general adult population. OBJECTIVE The objective of the study was to estimate the prevalence of hyperandrogenic states in late adolescence and youth and to evaluate potential independent predictors. DESIGN This was a cross-sectional study. SETTING The study was conducted in high schools. PATIENTS Patients included female students, aged 16-19 years. MAIN OUTCOME MEASURES The study protocol was designed with 3 possible levels of participation: the first level consisted of a self-compiled questionnaire; the second level added a medical examination; and the third level added a blood sample for laboratory testing. Liquid chromatography-tandem mass spectrometry was used to measure total testosterone, and a reference interval was established in-house. RESULTS We offered participation to 2052 students, and 1469 of those compiled the questionnaire. Of these, 1038 were examined, and 519 also provided blood samples. Two hundred three of the 1038 examined students and 125 of the 519 students who provided blood samples were subsequently excluded because of treatment with oral contraceptives or because of endocrine disorders. In the sample of women with a questionnaire + a medical examination, 13% were affected by isolated menstrual irregularity, 16.1% by isolated clinical hyperandrogenism, and 3.8% by both states. A similar prevalence of isolated menstrual irregularity (10.2%) and isolated clinical hyperandrogenism (16.7%) was found in the subsample of women with laboratory tests; in addition, 6.6% showed isolated hyperandrogenemia, and 4.3% proved to be affected by polycystic ovary syndrome. CONCLUSIONS This study provides for the first time a reliable assessment of the prevalence of hyperandrogenic states in late adolescent and young females and confirms that hyperandrogenic disorders originate at a young age.

Parallel Variations of Insulin-Like Peptide 3 (INSL3) and Antimüllerian Hormone (AMH) in Women With the Polycystic Ovary Syndrome According to Menstrual Cycle Pattern

CONTEXT Antimüllerian hormone (AMH) and insulin-like factor 3 (INSL3) represent ovarian functional markers of granulosa and theca cells, respectively. OBJECTIVE We conducted a prospective study to investigate AMH and INSL3 plasma levels in 3 groups of women with polycystic ovary syndrome (PCOS) classified according to menstrual cyclicity pattern and their relationship with ovarian morphology and hormonal levels. DESIGN AND PARTICIPANTS AMH and INSL3 were measured in a cohort of 57 patients with PCOS, divided into 3 groups according to menstrual status: eumenorrheic (PCOS-E, n = 15), oligomenorrheic (PCOS-O, n = 25), and amenorrheic (PCOS-A, n = 17). Clinical and endocrine characteristics and ovarian morphology were compared among the groups. Twenty-seven age- and weight-matched women without hyperandrogenism were included as controls. RESULTS According to the menstrual pattern, the women with PCOS-A and PCOS-O had higher INSL3 levels with respect to the control women (P = .025 and P = .004, respectively) and higher but not significant INSL3 levels compared with those of the women with PCOS-E. AMH levels were significantly higher in women with PCOS-A and PCOS-O with respect to those in women with PCOS-E (P < .001 and P < .001, respectively) and control women (P < .001 and P < .001, respectively). Interestingly, a significant positive correlation was found between INSL3 and AMH blood levels in all women with PCOS (R = 0.43; P = .002) and across the groups (R = 0.41; P < .001). CONCLUSIONS INSL3 and AMH levels are significantly correlated with each other in women with PCOS, and they are significantly increased, particularly in the presence of amenorrhea and oligomenorrhea. INSL3 and AMH may reflect a dysfunction of PCOS thecal and granulosa cells, which are responsible for the increased androgen production and chronic anovulation of this condition.

Psychological aspects of hyperandrogenic states in late adolescent and young women

The psychosocial implications of polycystic ovary syndrome (PCOS) phenotypes have been investigated in different patient populations, but little attention was paid to adolescent and young women. The aim of this study was to evaluate the psychosocial correlates of PCOS and other hyperandrogenic states in a population of late adolescent and young females and to provide a psychological characterization of specific clinical hyperandrogenic phenotypes.

No metabolic impact of surgical normalization of hyperandrogenism in postmenopausal women with ovarian androgen‐secreting tumours

To examine the impact of surgical normalization of testosterone on body weight and on glucose and lipid metabolism and insulin sensitivity in a group of hyperandrogenic women with ovarian androgen‐secreting tumours (OAST).

Polycystic ovary syndrome in familial partial lipodystrophy type 2 (FPLD2): basic and clinical aspects

ABSTRACT Polycystic ovary syndrome (PCOS) is a common disorder with a high phenotypic variability. Frequently, it is associated with a mild to moderate insulin resistance (IR) caused by an interaction between polygenic diathesis and the environment. However, PCOS may be a complication of an underlying syndrome of severe IR such as insulin receptor autoantibodies, mutations in the insulin receptor or in the signalling pathway downstream from the insulin receptor or, most frequently, a defect in function or in the development of the subcutaneous adipose tissue. Such conditions are clinically characterized by lipodystrophy. Lipodystrophy in some cases is produced by a single-gene defect. In our experience, PCOS secondary to a missense mutation in the LMNA gene, known as familial partial lipodystrophy type 2 (FPLD2), is the most frequent form of PCOS secondary to severe IR due to genetically determined lipodystrophy. These forms should be identified as they benefit from tailored therapies.