Increased cortisol level: a possible link between climacteric symptoms and cardiovascular risk factors.

OBJECTIVE: Vasomotor symptoms may increase the risk for cardiovascular diseases through still elusive mechanisms. Increased cortisol release may favor atherosclerosis. In this study, we tested whether vasomotor and psychological symptoms are associated with an increase in cortisol levels. METHODS: A cross-sectional investigation on women in early menopause enrolled consecutively between January and June 2009 was conducted. This study was set at a menopause outpatient service at University Hospital. Participants included 85 healthy women who were 6 months to 5 years postmenopause. The 24-hour urinary cortisol level and Greene Climacteric Scale scores were evaluated. Anthropometric parameters and fasting blood samples for the determination of high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, glucose, and insulin levels were measured. Body mass index, waist-to-hip ratio, and homeostatic model assessment of insulin resistance were calculated. The relation between Greene Climacteric Scale scores and 24-hour urinary cortisol level and between 24-hour urinary cortisol level and lipid levels or insulin resistance was determined. RESULTS: The Greene Climacteric Scale score for climacteric symptoms (coefficient of regression [CR], 1.343; 95% CI, 0.441-2.246) and body mass index (CR, 4.469; 95% CI, 1.259-7.678) explained 32.5% and 10.3%, respectively, of the variance in 24-hour urinary cortisol level (r = 0.428; P = 0.0003). Twenty-four-hour urinary cortisol level was inversely related to HDL-cholesterol level (CR, -0.065; 95% CI, -0.114 to -0.017; r = 0.283; P = 0.009) and was related to waist girth (CR, 0.685; 95% CI, 0.306-1.063) and homeostatic model assessment of insulin resistance (CR, 0.097; 95% CI, 0.032-0.162; r = 0.510; P = 0.0001). CONCLUSIONS: In early postmenopausal women, the Greene Climacteric Scale score is associated with increased 24-hour urinary cortisol level. Increased cortisol level is associated with known risk factors for cardiovascular disease, such as insulin resistance and decreased HDL-cholesterol level.

Menopause, estrogens, progestins, or their combination on body weight and anthropometric measures.

OBJECTIVE: To evaluate modification in body weight and anthropometric indexes in women at the time of menopause. DESIGN: Prospective longitudinal study. SETTING: Menopause Center at the University Hospital of Modena. PATIENT(S): Women in perimenopause (n = 87), ovariectomized (n = 60), and in postmenopause (n = 182) without and with treatment. INTERVENTION(S): Data were retrieved from the electronic database of the Menopause Center. MAIN OUTCOME MEASURE(S): Modification of weight, body mass index (BMI), waist, hip, and waist-to-hip ratio in 12 months. RESULT(S): Body weight increased in perimenopausal (0.6 +/- 0.1 kg) women, did not vary in postmenopausal (0.2 +/- 0.1 kg) women, and decreased in ovariectomized (-0.5 +/- 0.3 kg) women. Waist increased significantly in perimenopausal (2.3 +/- 0.4 cm) and in postmenopausal (2.0 +/- 0.4 cm) women. In comparison to no treatment, progestin administration (n = 29) decreased body weight (-0.2 +/- 0.5 kg) and hip (-1.1 +/- 0.9 cm) in perimenopausal women, estrogen (E) administration (n = 38) increased body weight (0.8 +/- 0.3 kg) in ovariectomized women, whereas E plus progestin administration (n = 89) did not induce any modification in postmenopausal women. CONCLUSION(S): Present preliminary data indicate that body weight increases in perimenopausal women, decreases in ovariectomized women, and does not increase significantly in naturally postmenopausal women. Estrogens and progestins influence body weight differently, increasing and decreasing it, respectively.

Cyclic progestin administration increases energy expenditure and decreases body fat mass in perimenopausal women.

OBJECTIVE: The menopause transition is characterized by luteal phase defect anovulatory cycles, and changes in body weight and body composition. Resting metabolic rate (RMR) is increased in the luteal phase of the menstrual cycle. We evaluated whether progestin administration increases RMR and influences body composition of perimenopausal women. DESIGN: Thirty-six perimenopausal women were randomly allocated to receive either calcium (1 g/day) continuously plus the progestin nomegestrol acetate (NOMAc; 5 mg/day for 10 days x month for 12 months) or calcium alone. Body composition, RMR, energy intake, and climacteric and psychological symptoms were evaluated at baseline and after 12 months. In the NOMAc group, body composition and RMR analyses were performed twice during the first month of treatment. One evaluation was performed after almost 8 days of NOMAc adjunct, and an another before or almost 15 days after NOMAc administration. RESULTS: Resting metabolic rate was increased by NOMAc administration of 54.5 +/- 73.8 kcal/24 h (P < 0.01). In women treated with NOMAc, fat mass decreased by 1.2 +/- 0.6 kg (P < 0.001). In comparison with controls, body weight (P < 0.05) and body mass index (P < 0.05) were also reduced after 12 months of therapy with NOMAc. CONCLUSIONS: In perimenopausal women the use of NOMAc increases RMR. During the menopause transition, cyclic NOMAc administration may contribute to reduce negative modification of body composition.

Sexual dimorphism in the levels of amniotic fluid leptin in pregnancies at 16 weeks of gestation: relation to fetal growth.

OBJECTIVE: To investigate whether in the first half of pregnancy levels of leptin in amniotic fluid are sexually dimorphic, and are related to fetal growth. STUDY DESIGN: Samples of amniotic fluid were collected during amniocentesis from 211 pregnancies with a single fetus with a normal karyotype (107 from male fetuses). Fetal growth was evaluated at 16 and 32 weeks of gestation, by sonography, and in a subset of 137 women at delivery. RESULTS: Amniotic fluid leptin was significantly lower in male than female fetuses (7.91+/-0.36 ng/ml versus 10.45+/-0.38 ng/ml; p = 0.0001). In females, levels of leptin were inversely related to BPD measured at 16 weeks (r = -0.241; p = 0.013) to biparietal diameter (BPD) (r = -0.281; p = 0.0076) and abdominal circumference (r = 0.268; p = 0.0107) measured at 32 weeks of gestation and to neonatal weight (r = -0.236; p = 0.051), neonatal weight/height (r = -0.271; p = 0.026) or neonatal Kaup index (r = 0.255; p = 0.045). Leptin was not related to any fetal parameter in males. CONCLUSIONS: Levels of leptin in amniotic fluid at 16 weeks of gestation are sexually dimorphic and are inversely related to fetal growth, particularly of females.

Does plasma insulin level affect ovarian response to exogenous administration of follicle-stimulating hormone in women without polycystic ovary syndrome?

BACKGROUND: Raised insulin levels have been shown to contribute to ovarian overproduction of androgens. Hyperinsulinemia, usually associated with polycystic ovary syndrome (PCOS), brings about greater ovarian endocrine and morphological responses to ovulation induced by follicle-stimulating hormone (FSH). This indicates that elevated levels of insulin play a role in the endocrine and paracrine control of the ovaries. OBJECTIVE: The aim of the present study was to investigate whether basal insulin levels influence ovarian response to FSH in healthy women (non-PCOS) undergoing assisted reproduction by in vitro fertilization-embryo transfer (IVF-ET). METHODS: The study included 36 consecutive women, 27-45 years old, undergoing IVF-ET for tubal-factor or male-factor infertility. Serum insulin levels were determined on the day of administration of gonadotropin-releasing hormone analog (GnRHa) and on the first day of FSH administration. RESULTS: Mean insulin levels were 6 +/- 3 and 7 +/- 3 microU/ml on the day of GnRHa and FSH administration, respectively. No correlations were found between basal insulin level, days of treatment, total FSH dose, estradiol level and the number of oocytes retrieved. CONCLUSIONS: The results of the present study show that normal levels of insulin do not seem to influence ovarian response to FSH in non-PCOS women. In all patients included in our study, serum insulin levels did not correlate with IVF stimulation data (days of stimulation, total FSH dose) nor with IVF-ET outcome. Thus the study demonstrates that, in patients who are not insulin-resistant, insulin does not correlate with ovarian response to FSH administration.

Comparison of the effect of oral and transdermal hormone therapy on fasting and postmethionine homocysteine levels.

OBJECTIVE: To compare the modifications on basal and post-methionine homocysteine (Hcy) levels induced by transdermal vs. oral continuous combined hormone therapy (HT). DESIGN: Prospective randomized study. SETTING: Outpatient service at university hospital. PATIENT(S): Twenty-four healthy postmenopausal women. INTERVENTION(S): Six-month administration of transdermal (50 microg/d of E(2) and 140-170 microg/d of norethisterone [NET] acetate; n = 12) or oral (2 mg of E(2) and 1 mg of NET acetate; n = 12) HT. MAIN OUTCOME MEASURE(S): Fasting levels of Hcy, cysteine (Cys), folate, and vitamin B12. Post-methionine Hcy concentrations. RESULT(S): During HT, a slight decrease of fasting Hcy (8.9 [6.7; 15.2] micromol/L vs. 8.3 [4.9; 12.0] micromol/L) and fasting Hcy/Cys, a possible index of Hcy trans-sulfuration (0.061 [0.039; 0.107] micromol/L vs. 0.048 [0.032; 0.093] micromol/L) was observed. Modifications were similar in the transdermal and oral group. Net decreases of Hcy and Hcy/Cys observed during HT were related linearly to pretreatment values (r = 0.821 and r = 0.775, respectively), and were significant for Hcy above, but not below, 9 micromol/L. Transdermal (33.5 [27.5; 75.9] micromol/L vs. 28.4 [17.4; 48.9] micromol/L) or oral HT (36.1 [17.7; 74.8] micromol/L vs. 29.9 [17.5; 50.3] micromol/L), decreased, similarly, post-methionine Hcy levels. CONCLUSION(S): Similarly to oral, transdermal HT reduces post-methionine Hcy and fasting Hcy when it is elevated.