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PCOS is the most common endocrinopathy among reproductive age women. Approximately 60% of PCOS women have insulin resistance. While the efficacy of metformin in reducing insulin resistance and decreasing androgen level has been widely validated, there is no agreement on the dose of metformin to be used.Prospective non-randomized cohort study of 108 insulin resistant, overweight and obese PCOS women, aged between 22 and 35 years. All patients received 1500 mg of metformin (500 mg x 3 times/day) for the first 6 months. At the end of this period, the patients' HOMA index was evaluated. In subjects, who did not demonstrate normalization of the HOMA index, the dose was increased to 2500 mg/day (500 mg at breakfast and 1000 mg at lunch and dinner) for additional 6 months. The hormonal blood profile, fasting insulin and fasting glucose levels, HOMA index, anthropometric assessment, pelvic ultrasound, FAI index and cholesterol were evaluated.Overall results showed a good response to metformin therapy in insulin-resistant PCOS patients with BMI25, while in patients with higher BMI (31.15 ± 0.40), no normalization of HOMA was found. At the higher dose of metformin, obese patients achieved a good response to therapy, with improvement in BMI, menstrual pattern, cholesterol levels and hyperandrogenism.Our results demonstrate a correlation between the required dose of metformin, BMI and hyperandrogenism. The dose of metformin should be adjusted to patients' BMI in order to obtain significant results in terms of clinical, metabolic and hormonal responses.

The primary aim was to evaluate changes in female sexuality across the menopausal period, and the secondary objective was to test the associations of female sexuality domains with vaginal atrophy and its symptoms.A cross-sectional multicenter study was performed involving 518 women, 40 to 55 years of age, consulting outpatient gynecological services at 30 centers across Italy. Vaginal atrophy was identified by the contemporaneous presence of a pH5, subjective vaginal dryness, and an objective sign. The relationships between vaginal atrophy and its main symptoms (vaginal dryness and dyspareunia), and Female Sexual Function Index (FSFI) score and its domains (desire, arousal, orgasm, dyspareunia, lubrication, and sexual satisfaction) were analyzed.The prevalence of sexual dysfunction, as defined by a FSFI score26.55, was 70.6%, increasing from 55% in the years 40 to 45, to 82.8% (P 0.01) in the years 52 to 55 of age. Mean FSFI score decreased from 40 to 45, to 46 to 48 years of age (23.13 ± 9.76 vs 19.49 ± 9.88; P 0.05), and from 48 to 51, to 52 to 55 years of age (21.3 ± 8.06 to 17.59 ± 9.11; P 0.01). Independent determinants of FSFI were age, vaginal atrophy, and the presence of vaginal dryness and dyspareunia (R2 0.208; P = 0.011). FSFI score was independently correlated (R2 0.116) with weight (CR -0.067; 95% confidence interval [CI] -0.126, -0.006; P 0.032), menopausal status (CR -2.406; 95% CI -4.180, -0.63; P 0.008), and vaginal dryness (CR -5.647; 95% CI -7.677, -3.618; P 0.0001). Vaginal dryness was the only variable correlated independently with each FSFI domain, including desire (also correlated with menopausal status), arousal (with age and menopausal status), lubrication (with age), orgasm (with age), satisfaction (with vaginal atrophy and being an ex-smoker), and dyspareunia (with age and spontaneously referred dyspareunia).In the perimenopausal years, FSFI score decreases and sexual dysfunction increases by about 30%. Vaginal dryness is the symptom of vaginal atrophy most closely related to all domains of female sexuality.

Herein, joint recommendations for diagnosis and treatment of vulvo-vaginal atrophy (VVA) in women in the peri- and post-menopausal phases from the Societa Italiana per la Menopausa (SIM) and the Societa Italiana della Terza Eta (SIGiTE) are presented. The recommendations are aimed at all healthcare personnel caring for women in the menopausal transition or postmenopausal phase, and are also intended to raise awareness of VVA. Recent data clearly indicate VVA is a highly prevalent condition among postmenopausal women, and that the vast majority of women with VVA are not adequately treated. In reality, diagnosis of VVA is simple and largely clinical. Many types of treatments are available for VVA, ranging from preventive education measures to local non-hormonal therapies, local agents that modulate hormonal receptors and systemic as well as laser therapy and radiofrequency. Regardless of the therapeutic approach adopted, greater communication between the physician and the woman with VVA should be actively encouraged. This is also in light of the difficulty of talking about the VVA and related disorders. Greater communication also encourages adequate therapy and thus minimizes the impact of VVA on the quality of life of the woman and her partner.

To analyze the sexuality of Italian menopausal women.Cross-sectional study.Menopausal women consecutively observed during the study period in menopause clinics.Women were interviewed about their current and premenopausal sexual activity: sexual intercourse frequency and self-rated sexual desire, capacity for orgasm and sexual satisfaction were recorded. Women were defined as having poor sexual functioning if they had one or less sexual intercourses per week or answered 'absent/poor' to the questions about the sexual domains.Oral hormone therapy (HT) use (odds ratio (OR) 0.43 for desire, 0.54 for orgasm and 0.56 for overall sexual satisfaction, all p0.001) and transdermal HT (OR 0.38, 0.53 and 0.53, respectively, all p0.001) were significantly associated with lower risk of poor sexual functioning. Higher physical and mental component scores (PCS and MCS, range 0-100) of the Short Form-12 are inversely related to poor sexual functioning (OR by point 0.96, 0.95, 0.95 for PCS and 0.96, 0.96 and 0.95, for MCS, respectively, all p0.001). Pain during and symptoms after sexual intercourse were significantly related to desire (OR 1.96 and 1.78, respectively), orgasm (OR 2.22 and 2.06, respectively) and sexual satisfaction (OR 2.02 and 1.79, respectively). The partner's health problems were associated with low sexual intercourse frequency (OR 4.18, p0.001) and absent/poor overall satisfaction (OR 2.61, p0.001).This study shows that, in menopausal Italian women attending menopause clinics, sexual function is associated with the quality of sexual life in reproductive age, partner's health status, current quality of life, HT and occurrence of pain during and symptoms after sexual intercourse.

BACKGROUND: In women with chronic anovulation, the choice of the FSH starting dose and the modality of subsequent dose adjustments are critical in controlling the risk of overstimulation. The aim of this prospective randomized study was to assess the efficacy and safety of a decremental FSH dose regimen applied once the leading follicle was 10-13 mm in diameter in women treated for WHO Group II anovulation according to a chronic low-dose (CLD; 75 IU FSH for 14 days with 37.5 IU increment) step-up protocol. METHODS: Two hundred and nine subfertile women were treated with recombinant human FSH (r-hFSH) (Gonal-f) for ovulation induction according to a CLD step-up regimen. When the leading follicle reached a diameter of 10-13 mm, 158 participants were randomized by means of a computer-generated list to receive either the same FSH dose required to achieve the threshold for follicular development (CLD regimen) or half of this FSH dose [sequential (SQ) regimen]. HCG was administered only if not more than three follicles >or=16 mm in diameter were present and/or serum estradiol (E(2)) values were or=16 mm in size at the time of hCG administration. RESULTS: Clinical characteristics and ovarian parameters at the time of randomization were similar in the two groups. Both CLD and SQ protocols achieved similar follicular growth as regards the total number of follicles and medium-sized or mature follicles (>/=16 mm: 1.5 +/- 0.9 versus 1.4 +/- 0.7, respectively). Furthermore, serum E(2) levels were equivalent in the two groups at the time of hCG administration (441 +/- 360 versus 425 +/- 480 pg/ml for CLD and SQ protocols, respectively). The rate of mono-follicular development was identical as well as the percentage of patients who ovulated and achieved pregnancy. CONCLUSIONS: The results show that the CLD step-up regimen for FSH administration is efficacious and safe for promoting mono-follicular ovulation in women with WHO Group II anovulation. This study confirms that maintaining the same FSH starting dose for 14 days before increasing the dose in step-up regimen is critical to adequately control the risk of over-response. Strict application of CLD regimen should be recommended in women with WHO Group II anovulation.

To analyze risk factors for type 2 diabetes among women attending menopause clinics in Italy for counselling about the menopause.Women attending a network of first-level outpatient menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms.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.Out of the 44 694 considered in this analysis, 808 had a diagnosis of diabetes type 2 (1.8%). In comparison with women aged50 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 agedor = 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).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.

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.

The choice between oral contraceptives (OC) containing 30 or 20 microg of ethinylestradiol (EE) is founded on clinical sign and medical history of the women. Not always a lower dose of EE cause less side effects than an higher dose. Often 20-microg-EE OC induces menstrual cycle alterations and sexual dysfunctions, inducing the women to stop the treatment. Low estrogens concentration have a negative effect on external genital tract, with a consequent vaginal dryness and dispareunia. It is known that OC with 20-microg of EE determine a lower increase of sex hormone binding globulin compared to 30 mg EE and the consequence can be a reduction in antiandrogen effect of OC. OC containing 30 microg of EE have a positive effect on peak in young women, particularly in lean subjects. Moreover, 30 microg of EE induce a better ovarian suppression associated with a lower steroidal production during the week of interruption. Besides, 30-microg-EE OC works well in blocking ovarian cysts formation in women with endocrine dysfunctions like polycystic ovary syndrome or with previous luteal cysts. In conclusion, an OC with 30 microg of EE and an antiandrogen progestin is better than another with 20 microg of EE with the same progestin, because 30 microg of EE have a more powerful antiandrogenic action and guarantee very good cosmetics and endocrine results.

To investigate whether inhibin B and activin A serum and follicular fluid levels in infertile women undergoing induction of superovulation correlate with successful ovulation.Infertile women (n = 16) (30-43 years of age) undergoing induction of superovulation for assisted reproduction were studied. A blood sample was collected before and days 3, 8, and 12 during the induction of superovulation. A follicular fluid sample at the time of ovarian pick up was also collected. Serum and follicular fluid were assayed for inhibin B, activin A, and estradiol.According to the successful follicular development women were divided in two groups: (A) responders (n = 10) and (B) poor responders (n = 6). Women of group A showed mean follicular fluid inhibin B levels higher than in group B (P = 0.001), while no significant difference for activin A levels was found. During induction of superovulation serum activin A levels did not change in both groups of women, while inhibin B and estradiol levels significantly increase only in responder women (P0.001). Serum inhibin B and estradiol levels correlated with follicles developedor = 10 mm (P = 0.000).Serum inhibin B is an effective marker of follicular development in infertile women undergoing induction of superovulation, and may represent a further marker for ovarian follicular capacity.

Flutamide is a non-steroid antiandrogen that specifically blocks the androgen receptor. We have investigated the effect of flutamide treatment on the adrenal androgen response to corticotrophin releasing factor (CRF) in eight patients with polycystic ovary syndrome (PCOS).Eight women with moderate to severe hirsutism, ranging in age from 19 to 23 years were enrolled in the study. Basal hormonal pattern showed anovulatory cycles, increased concentrations of LH, androstenedione and testosterone and increased LH/ FSH ratio. A baseline ultrasound scan revealed polycystic ovaries in all patients. Each received 250 mg of Flutamide twice a day for 6 months.Before treatment and at the end of the sixth month, women were evaluated for hirsutism score and a CRF test was performed to evaluate ACTH, cortisol and adrenal androgen responses.Androstenedione (delta 4), DHEA-S, 17-hydroxy-progesterone, testosterone and free-testosterone showed significantly reduced responses after six months of flutamide therapy whereas ACTH and cortisol response were similar to those before treatment. Clinical improvement in the degree of hirsutism was observed in all patients. The Ferriman-Gallwey scores decreased from a mean of 22 +/- 2 to 8 +/- 1.5.Flutamide induces a significant reduction in adrenal androgen response to the CRF test but not in the response of ACTH and cortisol. The finding that flutamide does not alter the pituitary-adrenal axis shows that flutamide acts by reducing adrenal androgens. These results demonstrate that flutamide is not only effective in the treatment of hirsutism but also reduces adrenal androgen secretion.

We report the results of administration of danazol after suspension of gonadotrophin-releasing hormone analogue (GnRHa) therapy for uterine myomas. A total of 21 women with uterine myomas was treated with 100 mg danazol for 6 months after GnRHa therapy. Uterine volume and endocrine status were monitored monthly by ultrasound and assay of plasma gonadotrophins, oestradiol and progesterone. The results show a rebound of uterine volume about 30% less than in controls at the end of danazol therapy. Menstrual cyclicity returned after 65 +/- 3 days in 16 subjects and five patients remained amenorrhoeic. Hormone assays confirmed renewed ovarian function in the women whose menstrual periods returned. Bone mineral content was substantially reduced during GnRHa treatment but improved significantly during danazol therapy even in the women who remained amenorrhoeic. These results show the utility of danazol in prolonging the therapeutic effects of GnRHa. The mechanism by which danazol inhibits rebound of uterine volume may be due to its antiprogesterone effects on uterine myomas.

Seventeen hyperprolactinemic patients aged from 24 to 58 years, with suspected pituitary adenoma, were studied. For diagnostic purposes, NOM and DOM tests were carried out, and also hypocycloidal tomography of the sella. In all cases in which the DOM test suggested the existence of a prolactinoma, the NOM test gave results in agreement with the former, except in one case. Hypocloidal tomography, although confirming the possibility of false negative (2 cases out of 17) or false positive results (1 case out of 17), demonstrated its diagnostic validity, although it was less sensitive than the biological tests.

The present study points out that the CHRONIC RENAL FAILURE (CRF) represents a situation of decreased adrenal function: at least for delta 5 Steroids which are markedly reduced when compared with normal subjects. Peripheral plasma levels of Pregnenolone (delta 5 P) ranged in CRF between 190 and 860 pg/ml; Dehydroepiandrosterone-sulphate (DHA-S) 0.1-2.2 ng/ml and Dehydroepiandrosterone (DHA) 200-3100 pg/ml. Cortisol was in the normal range or slightly elevated (70-175 ng/ml). A significant correlation between basal concentration and the time of dialysis was observed. It is interesting to notice how the phase levels of delta 5 P, DHA-S and DHA are reduced ad from the beginning of the haemodialysis treatment and that during such a treatment a further progressive decrease occurs reaching concentrations with are similar to those found in pre-puberty. This phenomenon appears to be the evidence of a progressive metabolic involution of the adrenal gland due to the exhaustion of enzymatic activities and of receptorial structures. Furthermore, these results suggest speculation on interrelationship between adrenal and gonadal activity in these patients.

The aim of this study was to evaluate the efficacy of a food supplement combination based on isoflavones and berberine (ISB) in the treatment of menopausal symptoms and dyslipidaemia. Isoflavones are extracted from soy and absorbed in the body after being activated by lactobacillus. Berberine, extracted from the plant Berberis aristata, lowers plasma cholesterol and triglycerides (TG) by increasing low-density lipoprotein (LDL) receptors and reducing hepatic synthesis of TG. One hundred twenty women with a mean age of 54.8 ± 0.6 years were enrolled and randomized to treatment with ISB (estromineral lipid [EL] = 60 cases) or calcium and vitamin D(3) (CaD = 60 cases). Menopausal symptoms, plasma cholesterol, and TG were evaluated at baseline, and after 4 and 12 weeks. EL treatment significantly lowered plasma total cholesterol (-13.5% ± 0.7 vs -0.2% ± 0.5), LDL cholesterol (-12.4% ± 1.5 vs + 0.8 % ± 0.7) and TG (-18.9% ± 2.5 vs -1.3% ± 1.2) and improved menopausal symptoms compared with CaD treatment. Safety parameters were unchanged during the study. The combination of berberine and isoflavones was effective in lowering cardiovascular (CV) risk factors in menopausal women with moderate dyslipidaemia and in improving their quality of life.

Purpose: The Italian Society of Contraception identified as one of its priorities the need to give recommendations on management of contraception during Coronavirus-Covid 19 pandemia Materials and methods: A concise communication was produced which summarises in an easy-to-read format suitable for clinicians the management of the different contraceptives mostly used. Information how to manage contraception in different conditions is presented. Results: Women may, in general, continue to use either intrauterine and or hormonal contraceptives. The use of condom should be added to any hormonal contraceptive, when the contraceptive efficacy is reduced or when women stop the contraceptive method. Conclusion: At the present time, during the Coronavirus-Covid 19 pandemia, no data contraindicate the use of intrauterine or hormonal contraceptives. Conversely the use of an appropriate contraception is advocate to prevent unintended pregnancies.

Background Dysmenorrhea and chronic pelvic pain occur in a significantly higher percentage in women with endometriosis; this benign condition has an incidence ranging from 5% to 10% in the general population, while 35% to 50% of infertile women are affected. Treatment of the symptoms demands integrated approaches with the use of anti-inflammatory substances or drugs and lifestyle changes, including attention to diet. The use of traditional anti-inflammatory drugs over the long term is not very successful because of the fear of side effects so they are almost always used with a short-term formula of 7-10 days when the woman's general condition becomes difficult to bear. In recent years, particular attention has been paid to natural substances with recognized anti-inflammatory activities that, associated with one another, are able to synergize individual actions. A nutraceutical containing substances capable of fighting chronic pelvic pain has recently been put on the market. The possible action mechanism derives from a synergy of action between alpha-lipoic acid, palmitoiletanolamide (PEA) and myrrh (Pelvinox, Laborest Italia srl, Nerviano, Milan, Italy), whose action is so effective that it is able to replace the use of anti-inflammatory drugs. The aim of the study was to evaluate the effect of these active ingredients in women with endometriosis and chronic pelvic pain. Methods This multicenter study saw the recruitment of 60 women (divided between the three centers participating in the study, Siena, Bologna and Udine) aged between 20 and 39 suffering from endometriosis (ovarian) and chronic pelvic pain. All the women took one nutraceutical (Pelvinox) at a dose of two tablets per day for 6 months. Results The results showed a significant reduction in pain symptoms as regards dyspareunia, dysmenorrhea and chronic pelvic pain, while there was no change in the mean diameter of the endometriosis cysts. Conclusions In light of the above, it is believed that substances such as alpha-lipoic acid, PEA and myrrh may play a very important role in this type of patient in the treatment of individual symptoms.

Reproductive alterations are a mainstay of the classic definition of polycystic ovary syndrome (PCOS), as defined in 1992 by the NIH consensus statement on PCOS [1]. These abnormalities still represent one of the three cardinal aspects used for diagnosing PCOS according to the current criteria, as defined by the Rotterdam ESHRE/ASRM consensus workshop [2] and by the AE-PCOS Society [3]. In addition, the reproductive alterations of PCOS are a key point in the treatment of this condition. Although there are several guidelines on the management of infertility in PCOS women, this issue remains controversial. Moreover, most of the documents on this topic were produced, by both the human reproduction societies and the endocrinology societies, with pregnancy as an immediate objective. However, reproductive abnormalities are frequently a central problem in these women beyond this specific aim, and come before and after this goal. Physicians are thus called to manage the reproductive alterations of PCOS women also when a pregnancy is not on the program, while taking into account comprehensively the whole spectrum of clinical problems of these patients. This concept is especially important for endocrinologists, who need to manage the many problems of these women for long periods, ideally for all of their lives. With the objective of reviewing the literature on the treatment of the reproductive alterations of PCOS, and developing evidence-based guidelines aimed at improving the management of these abnormalities, The Italian Society of Endocrinology (SIE) Board appointed a panel of experts, selected from researchers who published relevant articles in the field. The project and panel composition was also steered by the conviction that the clinical issues of PCOS should be managed with a network-oriented approach, primarily through strict interaction between endocrinologists and gynecologists.

The aim of this multicentre, prospective, randomised, investigator blind, controlled clinical trial was to evaluate the clinical efficacy and tolerability of a highly purified human menopausal gonadotrophin (hMG) preparation (Merional-HG) when administered to patients undergoing controlled ovarian stimulation (COS) for in-vitro fertilisation (IVF) procedure enrolled in hospital departments. One hundred fifty-seven patients were randomised in two parallel groups: 78 started COS with Merional-HG and 79 with Menopur. Results of the study showed that both highly purified hMG preparations were equivalent in terms of number of oocytes retrieved (primary endpoint: 8.8 ± 3.9 versus 8.4 ± 3.8, p = 0.54). In the patients treated with Merional-HG, we observed a higher occurrence of mature oocytes (78.3% versus 71.4%, p = 0.005) and a reduced quantity of gonadotrophins administered per cycle (2.556 ± 636 IU versus 2.969 ± 855 IU, p < 0.001). Fertilisation, cleavage, implantation rates and the number of positive β-human chorionic gonadotrophin (hCG; pregnancy) tests and the clinical pregnancy rate were comparable in the two groups. Both treatments were well tolerated. In conclusion, the results of this study support the efficacy and safety of Merional-HG administered subcutaneously for assisted reproduction techniques. Efficiency of Merional-HG appears to be higher due to reduced quantity of drug used and the higher yield of mature oocytes retrieved.

Objective To evaluate serum total inhibin (the sum of precursors, subunits, and mature molecules of inhibin) along with inhibin A and inhibin B in a large sample of women with polycystic ovary syndrome (PCOS) and to investigate whether these parameters differ between lean and overweight PCOS patients. Design Cross-sectional, controlled study. Setting Academic health centers in Siena and Bologna, Italy. Patient(s) A group of women with PCOS (n = 145) was divided according to body mass index (BMI) into "lean PCOS" (BMI 19–25 kg/m 2 , n=52) and "overweight PCOS" (BMI 26–51 kg/m 2 , n=93). A group of healthy women (n = 90) with BMI 19–24 kg/m 2 and a history of regular menstrual cycles and normal results on physical examination served as controls. Intervention(s) Blood samples were drawn between cycle days 3 and 5 in PCOS patients and controls. Main Outcome Measure(s) Serum concentrations of total inhibin, inhibin A, inhibin B, FSH, and LH were measured using commercially available immunoassays. Result(s) Women with PCOS had serum total inhibin levels twice as high as in the control group (median = 115 vs. 47 pg/mL). Dimeric inhibin A concentration was lower in the PCOS group compared with controls (10 vs. 25 pg/mL), whereas inhibin B concentration did not differ significantly between PCOS and control groups. There was no difference of either total inhibin or inhibin A levels between lean and overweight women with PCOS, whereas the inhibin B level was higher in the lean PCOS subgroup compared with the overweight PCOS subgroup. Total inhibin did not show any linear correlation with inhibin B, inhibin A, or serum gonadotropins. Conclusion(s) Women with PCOS have high serum concentration of total inhibin but not of inhibin A or inhibin B, thus suggesting that PCOS women have an impaired processing of α-inhibin precursor proteins.

To assess the efficacy of a product containing isoflavones and other plant extracts (BIO) on whole menopausal symptomatology and plasma lipids profile.Multicentre, randomized, double blind, placebo controlled clinical investigation on 125 menopausal women randomly assigned to two groups treated for 6 months with placebo or one tablet daily of an herbal product containing 72 mg/dose of isoflavones of different plants origin and other plant extracts (BIO). Primary end-point: Kupperman Menopause Index (KI) variations; secondary end-point: activity on plasma lipids profile and clinical global impression (CGI) on efficacy and tolerability by investigators and patients. The usual parametric test (paired Student t test) was performed to evaluate the significance. In case of non-applicability of parametric tests, the non-parametric Mann-Whitney U test was used. The differences where considered significant at p0.05 level.At the end of treatment in both groups KI showed a significant decrease (p0.001). However, in the BIO group the KI reduction was significantly higher (p=0.0265) than in the placebo group after 4 and 6 months of treatment. In the BIO treated patients the LDL cholesterol showed a borderline but not significant reduction compared to placebo (p=0.0608) and triglyceride (TG) a significant (p=0.0151) decrease compared to placebo. The investigator's and patient's CGI on BIO group where superior as compared to placebo. Clinical tolerability was good in booth groups.On the basis of positive effects on KI and lipids profile as well as of good clinical tolerability, BIO can be considered one of the possible alternative therapy for conventional HRT.

Objective: To evaluate the course of changes in serum inhibin A, inhibin B, and pro-αC levels in women with surgically or pharmacologically induced menopause. Design: Longitudinal study. Setting: Academic Health Center of Siena, Siena, Italy. Patient(s): Four groups of women were studied: [1] surgical menopause including bilateral oophorectomy (n = 15), [2] amenorrhea induced by GnRH-analogue for treatment of endometriosis (n = 13), [3] amenorrhea induced by antineoplastic chemotherapy before (n = 15) and after chemotherapy (n = 13), and [4] control physiological menopause (n = 67). Intervention(s): Collection of blood specimens. Main Outcome Measure(s): Serum inhibin A, inhibin B, and pro-αC concentrations were measured by using specific two-site ELISAs. Result(s): Following oophorectomy, serum inhibin A, inhibin B, and pro-αC levels were decreased on the first postoperative day; on the fifth postoperative day they were still significantly reduced. Women with amenorrhea induced by GnRH-analogue treatment exhibited serum inhibin A and pro-αC levels that were significantly higher than those observed in physiological menopause. Patients undergoing antineoplastic chemotherapy had higher serum inhibin A levels than those in physiological menopause, whereas inhibin B and pro-αC levels did not differ. During the course of chemotherapy, median serum inhibin A concentrations were similar to those of patients evaluated after the suspension of treatment. In postmenopause, inhibin A, and inhibin B levels were low, whereas levels of pro-αC were still detectable. Conclusion(s): Circulating levels of inhibin A, inhibin B, and pro-αC are reduced after oophorectomy. Women with amenorrhea induced by GnRH-analogue treatment or by antineoplastic chemotherapy still produce inhibin A and pro-αC. This probably reflects a residual ovarian function and hormone synthesis. Therefore, the ovary may be a source of pro-αC after menopause; significant amounts of pro-αC are present in circulation after natural menopause, but not after oophorectomy.

Estrogen replacement therapy after menopause reduces the incidence of arterial disease and cerebrovascular events. The reduced incidence also seems to be due to a positive effect of estrogens on brain blood flow as shown by a decrease in the carotid artery pulsatility index. Raloxifene, a second-generation selective estrogen receptor modulator, has aroused considerable interest because of its tissue-specific agonist-antagonist effect on estrogen receptors. However, there have been no studies on the effect of raloxifene on carotid blood flow after menopause.A total of 66 healthy women in postmenopause for more than a year were divided randomly into 2 groups: the first group (n = 33; mean age +/- SD, 53.3 +/- 5.2 years) was treated with raloxifene (one 60-mg capsule per day) for 6 months, and the other group (n = 33; mean age +/- SD, 51.9 +/- 4 years) was untreated. Doppler ultrasonography was used to measure carotid artery pulsatility index (PI) at the beginning of the study and at 2-month intervals.A reduction in carotid artery PI was observed in all patients receiving raloxifene. No significant changes were observed in the control group. The reduction with respect to baseline values was 6.1%(P.05) after 2 months, 11.2% (P.05) after 4 months, and 13.2% (P.05) after 6 months of therapy. The higher the baseline PI, the greater was its reduction after therapy.After 6 months of therapy, raloxifene induced a reduction in PI similar to that reported after estrogen therapy. The present results further our understanding of the mechanisms by which raloxifene might reduce the incidence of cardiovascular disease in postmenopausal women.

Oestrogen plays a role in modulating growth hormone (GH), luteinizing hormone (LH), folliclestimulating hormone (FSH) and osteocalcin secretion in women. Indeed, the postmenopausal period is characterized by changes in plasma GH, LH, FSH and osteocalcin levels. The aim of the present study was to investigate the changes in the secretory patterns of these hormones in postmenopausal women under different therapeutic regimens. A total of 20 subjects took part in the study. They were subdivided into four groups comprising 5 untreated postmenopausal women (time since menopause 1–5 years), 5 postmenopausal women receiving steroid hormone replacement therapy, 5 postmenopausal women receiving salmon calcitonin and 5 fertile women with regular menstrual cycles. Blood samples were collected every 15 min for 4 h and hormone levels were measured by radioimmunoassay. Plasma GH levels fell in the postmenopausal women, but were restored under oestrogen-progestogen treatment. The pulsatile patterns of plasma LH and FSH did not show significant differences in the treated and untreated women. Plasma osteocalcin levels showed episodic fluctuations and mean levels decreased under steroid hormone or calcitonin treatment. No significant correlation was observed between plasma GH and osteocalcin or gonadotrophin levels or body mass index.

The goal of this study was to evaluate the effects of menstrual cyclicity on plasma beta-endorphin (beta-EP) levels. For this purpose, beta-EP and cortisol plasma concentrations were measured during the menstrual cycle in healthy control subjects (n = 12), in patients affected by anovulatory syndrome (n = 6), and in amenorrheic patients (n = 8). In the same patients, beta-EP and cortisol were also measured under treatment for the induction of ovulation with pulsatile luteinizing hormone-releasing hormone or human menopausal gonadotropin plus human chorionic gonadotropin administration. In spontaneous and pharmacologically induced ovulatory cycles, a significant preovulatory rise of plasma beta-EP levels was always evident. Constant levels were found in the other periods of ovulatory cycles and in the patients affected by anovulatory syndrome and primary amenorrhea. Cortisol levels did not show any significant change throughout the cycle, either in controls or in patients before or after treatment. This result suggests that when ovulation occurs, plasma beta-EP levels show a relevant rise, the physiologic significance of which remains to be elucidated.

The cause of the amenorrhea that occurs in patients with hyperprolactinemia is unknown. The involvement of endogenous opioid peptides in the inhibition of GnRH release as a central factor leading to the hypogonadotropic state has been recently described. This study analyzed the LH response to opiate receptor blockade by naloxone (4 mg, iv) in groups of subjects with amenorrhea due to hyperprolactinemia of different etiologies. Patients presenting with a PRL-secreting pituitary adenoma (n = 7), idiopathic hyperprolactinemia (n = 9), or hyperprolactinemia during pharmacological treatment for schizophrenia (n = 5) were studied. Furthermore, to evaluate whether high circulating PRL levels influence the activity of the opioid system after the menopause, a group of seven postmenopausal subjects was tested before and 1 week after the administration of metoclopramide (10 mg, three times a day), a dopamine receptor antagonist. Normal premenopausal women (n = 6) served as controls. Naloxone significantly increased plasma LH levels in both prolactinoma and idiopathic hyperprolactinemic patients (P less than 0.01 vs. basal and placebo). In neither of those groups was a significant correlation found between the plasma LH response to naloxone and basal plasma PRL levels. In contrast to pathological hyperprolactinemia, blockade of opiate receptors did not significantly change LH secretion in either amenorrheic women with pharmacologically induced hyperprolactinemia or postmenopausal women. These results suggest that the effect of hyperprolactinemia on opioid modulation of LH secretion is related to the nature of the hyperprolactinemic state, supporting the existence of increased opioid inhibition of LH levels in pathological hyperprolactinemia.