Factors associated with climacteric symptoms in women around menopause attending menopause clinics in Italy.

OBJECTIVE: To obtain data on correlates of climacteric symptoms in women around menopause attending menopause clinics in Italy. METHODS: Since 1997 a large cross sectional study has been conducted on the characteristics of women around menopause attending a network of first level menopause outpatient's clinics in Italy. A total of 66,501 (mean age 54.4 years) women are considered in the present paper. RESULTS: The odds ratios of moderate and severe hot flashes/night sweats were lower in more educated women and (for severe symptoms only) in women reporting regular physical activity. Depression, difficulty to sleep, forgetfulness and irritability tended to be less frequent in more educated women and (depression only) in women reporting regular physical activity. Parous women reported more frequently these symptoms. CONCLUSIONS: This large study confirms in Southern European population that low education, body mass index and low physical activity are associated with climacteric symptoms. Parous women are at greater risk of psychological symptoms.

Risk factors for type 2 diabetes in women attending menopause clinics in Italy: a cross-sectional study.

OBJECTIVE: To analyze risk factors for type 2 diabetes among women attending menopause clinics in Italy for counselling about the menopause. SUBJECTS: Women attending a network of first-level outpatient menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms. METHODS: Cross-sectional study with no exclusion criteria. Type 2 diabetes was defined according to National Diabetes Data Groups Indications and the fasting blood glucose at an oral glucose tolerance test within the previous year. RESULTS: Out of the 44 694 considered in this analysis, 808 had a diagnosis of diabetes type 2 (1.8%). In comparison with women aged < 50 years, the multivariate odds ratios (OR) of type 2 diabetes were 1.31 (95% confidence interval (CI), 0.99-1.74) for women aged 50-52 years, 1.66 (95% CI, 1.27-2.17) at 53-56 years and 2.84 (95% CI, 2.20-3.67) in women aged > or = 57 years. Type 2 diabetes was less frequently reported in more educated women (OR high school/university vs. primary school = 0.44 (95% CI, 0.36-0.55)). Being overweight was associated with an increased risk of type 2 diabetes. In comparison with women reporting a low level of physical activity, the multivariate OR of type 2 diabetes was 0.67 (95% CI, 0.54-0.84) for women reporting regular physical activity. In comparison with premenopausal women, the multivariate OR of type 2 diabetes was 1.38 (95% CI, 1.03-1.84) in women with natural menopause. This finding was present also after allowing for the potential confounding effect of age. The multivariate OR of diabetes for users of hormonal replacement therapy was 0.58 (95% CI, 0.46-0.73). CONCLUSIONS: This large cross-sectional study suggests that postmenopausal women are at higher risk of type 2 diabetes after allowance for the effect of age. Other main determinants of risk of type 2 diabetes in women around menopause were low socioeconomic status and being overweight. Diabetes was found less frequently in those taking hormone replacement therapy.

Neuroendocrine effects of different estradiol-progestin regimens in postmenopausal women.

OBJECTIVE: New regimens and routes of administration of hormonal replacement therapy (HRT) in climateric women are becoming available. Since there is no information on the neuroendocrine effects of sequential combined treatment with 17 beta-estradiol and a progestin, the present study evaluated the neuroendocrine, clinical vasomotor and psychological changes before and after different sequential combined HRT regimens (17 beta-estradiol plus nomegestrol acetate, or cyproterone acetate, or vaginal progesterone). Vasomotor and behavioral effects were evaluated by using the Kupperman score, while changes in plasma endorphin (beta-END) levels were used as marker of neuroendocrine effects. METHODS: Postmenopausal women (n = 30) were randomly divided into three groups (ten women for each group); all women received continuous 17 beta-estradiol (50 mg, transdermal) and each group was sequentially treated with different progestins for 12 days/month: group A, cyproterone acetate (5 mg p.o.); group B, nomegestrol acetate (5 mg p.o.); and group C, progesterone (100 mg, vaginal cream). A group of healthy fertile women (n = 8) served as control. Before and after 6 months of HRT, postmenopausal women underwent an evaluation of subjective Kupperman score and two neuroendocrine tests: (a) naloxone (4 mg i.v.) and (b) clonidine (1.25 mg i.v.). Plasma beta-END levels were measured before and at 15, 30, 45, 60 and 90 min after drug injection. Control women were studied by administering the two neuroendocrine tests only once. RESULTS: Postmenopausal women before HRT showed a pathological Kupperman and no changes of plasma beta-END levels in response to the clonidine and naloxone tests score. On the contrary the increase was significant in healthy women. In each of the three groups of treated women both naloxone and clonidine tests induced a significant increase in plasma beta-END levels (P < 0.01). After 6 months of HRT, an improvement of vasomotor and psychological symptoms was shown by a decrease of Kupperman score. CONCLUSIONS: The present study indicates that sequential treatment with transdermal 17 beta-estradiol and progestin, no matter which progestin was used, restores the beta-END release, improves vasomotor and psychological symptoms.

Plasma beta-endorphin and beta-lipotropin levels increase in well trained athletes after competition and non competitive exercise.

Plasma beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) levels were measured in 15 healthy trained marathon runners. These hormones were evaluated in two different conditions: 1-before (1h) and after a marathon race (n = 10); 2-before, during and after a prolonged (90 min) submaximal exercise (bicycle ergometer at 50% VO2 max) (n = 5). In these latter group plasma beta-EP and beta-LPH levels were measured every 15 min for 165 min. In all the athletes, both plasma beta-EP and beta-LPH levels were significantly higher after the end of the marathon race than in basal conditions (p less than 0.01). The prolonged exercise with bicycle ergometer significantly stimulated plasma beta-EP and beta-LPH levels. Starting 60 min after the beginning of the exercise, plasma beta-EP and beta-LPH levels resulted significantly higher than basal values until the end of the exercise (p less than 0.01 at 60, 75 and 90 min). These data confirming that marathon running is a potent stress stimulus, showed that the duration and related factors but not the work load may be considered critical in stimulating beta-EP and beta-LPH release during physical exercise.

Effect of oral contraceptives or dexamethasone on plasma beta-endorphin during the menstrual cycle.

Several studies have showed a significant increase of plasma beta-endorphin levels during the periovulatory days of the menstrual cycle. The aim of the present study was to investigate the origin of the periovulatory changes of plasma beta-endorphin, trying to discriminate between a possible ovarian and/or pituitary origin. Daily plasma beta-endorphin, luteinizing hormone (LH), and cortisol levels were measured from the 8th to the 20th day of the menstrual cycle in healthy normal-cycling women (10 cases) before and during dexamethasone (DEX; 6 cases) or estroprogestinic treatment with monophasic (5 cases) or triphasic (5 cases) pill. In the control menstrual cycle, during the preovulatory days, a significant increase of plasma beta-endorphin was found. While oral contraceptives abolished the midcycle increase of plasma beta-endorphin, the periovulatory plasma beta-endorphin peak was present during DEX treatment. Plasma cortisol levels did not show any significant change throughout the control menstrual cycle, while they were significantly lowered by the DEX administration and significantly increased during estroprogestinic treatment. These results suggest that the increase of plasma beta-endorphin during the periovulatory days is related to the ovulatory function, and suggest a possible ovarian origin.

Plasma B-endorphin resistance to dexamethasone suppression in obese patients.

Patients with simple exogenous obesity are characterized by increased B-endorphin (B-EP) plasma levels, despite normal ACTH and B-Lipotropin (B-LPH). To evaluate the origin of such an hyperendorphinemia, 42 obese patients were submitted to a short overnight dexamethasone suppression test (DST: 1 mg at 23:00 h). Blood samples were taken in basal conditions and 9, and 17 h after DST. The same procedure was applied in 12 healthy, normal weight volunteers. In further five patients, 0.5 mg per 4/die were given. B-EP was measured by radioimmunoassay (RIA) after silicic acid extraction and Sephadex G-75 column chromatography. ACTH and Cortisol were measured by direct IRMA and RIA, respectively. Basal B-EP levels of patients (24.2 +/- 16.5, fmol/ml, M +/- SD) were double than in normal weight controls (10.8 +/- 4.6), while ACTH and cortisol fell in the normal range. ACTH and cortisol were significantly reduced by DST in both patients and controls, while B-EP in patients did not. Cortisol, however, was not suppressed in 7 patients (16%). At 08:00, the suppression of B-EP in controls was 49.0 +/- 18.4%, while in obese patients it was only 21.2 +/- 38.8% (p less than 0.01). However, patients with weight excess below 50% normally suppressed B-EP (41.6 +/- 15.3%), while those with weight excess over 75% did not (11.3 +/- 47.5%). The doubling of dexamethasone intake does not lead to a suppression of plasma B-EP in these last patients. These data indicate the existence of neuroendocrine abnormalities in the hypothalamus-pituitary-adrenal axis of obese patients and suggest that their hyperendorphinemia originates outside the anterior pituitary.

Seminal fluid androgen levels in infertile patients.

Seminal fluid concentrations of testosterone (T), dihydrotestosterone (DHT), androstenedione (A), and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) were measured in 34 male patients of infertile couples. Patients were subdivided into oligospermic (less than 20 X 10(6)/mL) and asthenospermic (typical motility less than 20%; total motility less than 40%) groups. Steroids were measured by specific radioimmunoassay after ether extraction and celite column chromatography. 3 alpha-Diol was present in seminal fluid, and its concentration was significantly correlated with DHT (r = .49, P less than .05). In oligospermic patients, seminal levels of T (78 +/- 29 pg/mL, mean +/- SD) and DHT (323 +/- 132 pg/mL) were significantly reduced in comparison with normospermic men (T, 119 +/- 56, P less than .05; DHT, 557 +/- 255, P less than .01), while A and 3 alpha-diol concentrations were similar in the two groups. Seminal T and DHT levels were also reduced in asthenospermic specimens, which showed increased 3 alpha-diol concentrations (75 +/- 44 pg/mL) with respect to normokinetic samples (45 +/- 20, P less than .05). Finally, a positive linear relationship was observed between DHT and both sperm density (P less than .01) and total motility (P less than .01). These data demonstrate the existence of a significant amount of 3 alpha-diol in seminal plasma and suggest DHT as the androgen most closely related to sperm quality.

Opioid control of luteinizing hormone secretion in patients with hirsutism and hyperandrogenemia.

The present study was designed to evaluate the influence of hyperandrogenemia on the activity of the opioid system regulating LH secretion in menstruating women. Ten subjects presenting with hirsutism and hyperandrogenemia and 9 healthy normally cyclic subjects participated in the study. Naloxone or saline was administered on 2 different days both during the follicular (6-8 days after menstrual bleeding) and during the luteal phase of the menstrual cycle. Naloxone significantly increased plasma LH levels in the luteal, but not during the follicular phase of the cycle in both subject groups. It may be inferred from these observations that opioid-mediated inhibition of LH secretion is not altered in menstruating hyperandrogenic patients, suggesting that the circulating androgens are not an important determinant of the functional neuroendocrine activity of the opioid system.

Reduced estriol and dehydroepiandrosterone sulphate plasma levels in methadone-addicted pregnant women.

The plasma levels of human chorionic somatomammotropin (hCS), estriol (E3), dehydroepiandrosterone sulphate (DHA-S), cortisol and the circadian changes of the two last adrenal hormones were studied in 25 pregnant methadone-addicted women (MA) and 21 pregnant drug-naive controls (C) at different periods of gestation and in 13 non-pregnant women (7 MA and 6 drug-naive). MA pregnant women showed normal plasma levels of hCS both at the second (6.9 +/- 0.1 vs. 7.2 +/- 0.1 micrograms/ml) and third (9.6 +/- 0.2 vs. 9.3 +/- 0.2) trimester, while plasma concentrations of E3 at term were lower than normal (MA: 4.4 +/- 0.8; C: 8.2 +/- 1.0 ng/ml, P less than 0.05). DHA-S plasma levels of MA pregnant women were half the normal values in three trimesters of gestation, while there were no differences in non-pregnant subjects. Circadian variations of cortisol and DHA-S plasma levels were present in both MA and C. The blunted DHA-S but normal cortisol plasma levels found in MA pregnant women indicate that opiate abuse interferes with adrenal function, mainly of the fetus. Due to the scarce availability of adrenal precursors, these data suggest that E3 measurements should not be considered as a useful index of fetal well-being in the presence of opiate addiction.

Short-term effects of ovariectomy: the opioid control of LH secretion in fertile climacteric and postmenopausal women.

The aim of this study was to evaluate the activity of opiate receptors involved in the regulation of LH secretion in relationship to ovariectomy. Menstruating fertile (n = 5) and climacteric (n = 7) patients and postmenopausal (n = 5) women who underwent therapeutical bilateral ovariectomy were studied in the first week postsurgery and LH plasma levels were evaluated after naloxone (4 mg in bolus plus 4 mg infusion/90 min), LHRH (10 micrograms + 10 micrograms iv) and saline administration. Two groups of fertile (n = 6) and postmenopausal (n = 6) subjects were studied as controls. Since the LH responsiveness to naloxone was impaired in climacteric patients after ovariectomy, the test was repeated in 5 of them after 1 and 6 months of estrogen-gestagen treatment (conjugated estradiol + noretisterone acetate), showing a significant increase in all patients in both cases. In four subjects treated with only gestagen, naloxone was still unable to significantly modify LH plasma levels. These results indicate that ovariectomy affects the activity of opiate receptors, resulting in the first week postsurgery LH rise inversely related to basal LH levels. Furthermore, these results indicate that one or six cycles of estrogen-gestagen treatment in ovariectomized patients similarly induces a restoration of the opiate receptors neuroendocrine activity.

Impairment of opioid control of luteinizing hormone secretion in menstrual disorders.

With the aim of examining central opioid influences on the control of luteinizing hormone (LH) secretion, we evaluated the LH response to naloxone, an opioid receptor antagonist, in patients affected by normo-, hyper-, and hypogonadotropic amenorrhea, polycystic ovarian disease and hyperprolactinemia. The results indicate that opioid influences are altered in well-defined pathologic conditions (hyperprolactinemia, obesity), in addition to being modified by gonadal steroids.