Overview of elagolix for the treatment of endometriosis.

INTRODUCTION: Suppression of sex-steroid secretion is required in a variety of gynecological conditions. This can be achieved using gonadotropin releasing hormone (GnRH) agonists that bind pituitary gonadotropin receptors and antagonize the link-receptor of endogenous GnRH, inhibiting the mechanism of GnRH pulsatility. On the other hand, GnRH antagonists immediately reduce gonadal steroid levels, avoiding the initial stimulatory phase of the agonists. Potential benefits of GnRH antagonists over GnRH agonists include a rapid onset and reversibility of action. Older GnRH antagonists are synthetic peptides, obtained by modifications of certain amino acids in the native GnRH sequence. They require subcutaneous injections, implantation of long-acting depots. The peptide structure is responsible for histamine-related adverse events and the tendency to elicit hypersensitivity reactions. AREAS COVERED: Research has worked towards the development of non-peptidic molecules exerting antagonist action on GnRH. They are available for oral administration and may have a more beneficial safety profile in comparison with peptide GnRH antagonists. This article focuses on the data of the literature about elagolix, a novel non-peptidic GnRHantagonist, in the treatment of endometriosis. EXPERT OPINION: Elagolix demonstrated efficacy in the management of endometriosis-associated pain and had an acceptable safety and tolerability profile. However, further studies are necessary to evaluate its non-inferiority in comparison with other endometriosis's treatments.

[Bacterial vaginosis: efficacy of a local treatment with a gel containing a fraction derived from propinibacterium acnes]. / Vaginosi batterica: efficacia di un trattamento locale con un gel vaginale a base di una frazione batterica derivata da Propionibacterium acnes.

BACKGROUND: Bacterial vaginosis (BV) is favored by a decreased activity of vaginal immune system. The fraction derived from Propionibacterium acnes is known to activate the immune system and is used parenterally to treat respiratory and urinary infections. The employ of a fraction derived from Propionibacterium acnes locally, in the context of the vaginal immune system, is made possible by a vaginal gel in which this fraction is associated with hyaluronic acid, well-known for its moisturizing activity, and polycarbophil, capable of miming the function of cervical mucus. The aim of the study was to evaluate whether this preparation is efficacy in the treatment of vulvovaginal symptoms associated to BV. METHODS: After the diagnosis of BV and the evaluation of a Visual Analogic Score >6 for vulvovaginal itch and burning, 33 women participated in this study on a voluntary basis. They were treated with a vaginal gel (Immunovag®, Depofarma, Italy) for 5 days, with one vulvovaginal application a day. RESULTS: The day following the last application, the subjects reported a significant reduction of vulvovaginal symptoms and a significant reduction of vulvovaginal erythema and leucorrhea. In the vaginal swab performed before the treatment, anaerobic microorganisms were positive in 82% and negative in 18% of cases; when tested the day following the end of treatment, it was positive in 25% and negative in 75% of subjects. Symptom reduction rates did not differ between the groups with positive or negative vaginal swab. The results obtained in the subjects treated with Immunovag® were similar to those obtained in a group of women with BV treated with clindamycin cream (one daily vulvovaginal application of 100 mg, for 5 days). CONCLUSIONS: The activation of the vaginal immune system induced by Immunovag® can antagonize the symptoms of BV and counteract the growth of vaginal anaerobic microorganisms.

Effect of Estradiol valerate plus dienogest on body composition of healthy women in the menopausal transition: a prospective one-year evaluation.

In the menopausal transition (MT), combined oral contraceptive (COC) should be chosen accordingly to its neutrality on liver metabolism and to its ability to counter the increase of fat mass (FM) that occurs in this reproductive period of life. This prospective multi-centric observational study was conducted on 36 women in their MT at the Universities of Cagliari, Modena and Naples. The body weight (BW), the Body Mass Index (BMI), the waist to hip ratio (WHR), the measurement of body composition (BC) with the Multi-frequency Bioelectrical Impedance (MF-BIA) were performed before, at the 6th and at the 12th month of the study in which a group of women (control group; N.18) did not assume COC, whereas the other 18 women assumed the four-phasic COC containing estradiol valerate (EV) associated with dienogest (EV/DNG group). In comparison to controls in the EV/DNG group, a significant decrease (p < 0.05) of BW (58.8 ± 7.6 to 57.3 ± 7.0), BMI (24.1 ± 2.7 to 23.5 ± 2.8), WHR (0.82 ± 0.052 to 0.79 ± 0.048) and FM (17.7 ± 5.4 to 16.4 ± 5.6) was observed. In controls, FM significantly increased (17.0 ± 11 to 17.7 ± 2.7; p < 0.05). In conclusion, these results suggest that the anti-androgenic and progestinic activities of DNG associated with a weak estrogenic activity of EV, is a contraceptive method capable of counteracting the negative changes of BC occurring in the MT.

Clinical effect of hormonal replacement therapy with estradiol associated with noretisterone or drospirenone. A prospective randomized placebo controlled study.

The study was performed to compare the clinical effect of a hormone replacement therapy (HRT) with two different progestins. Postmenopausal women (PMW) with climacteric symptoms (CS) randomly received for 12 months orally, either placebo (n = 20), 1 mg estradiol (E) plus 0.5 mg noretisterone acetate (NETA; n = 40), or 2 mg drospirenone (DRSP; n = 40), a testosterone- and spironolactone-derived molecule, respectively. Weight (W) declined only during E/DRSP (p < 0.04 versus placebo). Fat mass (FM) decreased, similarly, during E/NETA and E/DRSP. Intracellular water (ICW) did not change, while extracellular water (ECW) decreased during E/DRSP (p < 0.0001) (p < 0.002 versus E/NETA). During E/NETA and E/DRSP, similar decreases were observed for insulin resistance (IR) by the homeostatic model assessment for IR (HOMA-IR) (p < 0.0001 versus placebo for both), systolic (p < 0.04 versus placebo for both) and diastolic (p < 0.002) blood pressure (BP). Lipids did not change. In comparison to placebo CS, by the Kupperman Index (KI), significantly declined (p < 0.0001) during E/NETA or E/DRSP. Menopause-specific Quality of Life (MENQoL) significantly declined versus placebo (p < 0.04) during both E/NETA and E/DRSP. In conclusion, differences between the two progestins are mainly limited to body composition (BC), where the addition of DRSP decreases ECW and body W (BW).

Observational study on the efficacy of the supplementation with a preparation with several minerals and vitamins in improving mood and behaviour of healthy puerperal women.

We investigated whether a formulation containing vitamins and minerals (vit&min) could improve the worsening of mood changes occurring after delivery ("a.d."). The study was performed in 552 healthy non-anaemic puerperal women ("p.w") without risk factors for puerperal depression ("p.d"). They were at their first full-term pregnancy, and spontaneously delivered healthy newborns. The Edinburgh Depression Postnatal scale (EPDS) evaluates the psychological status of "p.w". EPDS was administered the 3rd (visit 1), 15th (visit 2) and 30th (visit 3) day "a.d.". An EPDS >12 indicates a major susceptibility to "p.d". At the same time intervals, haemoglobin, iron and ferritin (haematological parameters) levels were evaluated. After visit 1, the subjects were randomized to vit&min treatment (group A; N.274) or to calcium/vitamin D3 treatment (group B; N.278). In both groups haematological parameters significantly increased without differences between the groups. EPDS score improved in both groups, but in the group A, the EPDS decrease was significantly larger (p < 0.05) in comparison to the group B. This effect is mainly evident in subjects with a basal EPDS ≥ 12. An early examination of psychological condition could select "p.w." with a high susceptibility to neuronal changes occurring postpartum. Vit&min favourably modulates brain functions antagonizing the evolution to "p.d".

Pharmacokinetic evaluation of ulipristal acetate for uterine leiomyoma treatment.

INTRODUCTION: Progesterone (P), and its receptors (PRs), play a key role in uterine leiomyoma growth. Selective progesterone receptor modulators exert mixed antagonist and agonist effects on the PRs. Mifepristone, a PR-antagonist, reduces leiomyoma volume and related symptoms. Ulipristal acetate (UPA) exerts a potent antiprogestin activity, with less antiglucocorticoid activity compared to mifepristone. This property provides potential advantages for long-term use. AREAS COVERED: This paper focuses on the effect of UPA on leiomyoma's growth and related symptoms in women. The authors also evaluate UPA's efficacy in reducing leiomyoma's size and menorrhagia in Phase II/III trials. EXPERT OPINION: In the authors' opinion, UPA (5 mg/day) over 3 months can be used to plan the surgery in women with symptomatic leiomyomas. The tolerability and the safety of treatment over a period longer than 3 months have to be evaluated. The results of the follow-up treatment suggest that further studies could successfully evaluate the efficacy and the tolerability of intermittent 3-month courses of treatment.

Endocrinological, metabolic and clinical features of treatment with oral contraceptive formulation containing ethinylestradiol plus chlormadinone acetate in nonobese women with polycystic ovary syndrome.

BACKGROUND: Chlormadinone acetate (CMA) is a progestin compound similar to progesterone, with antiandrogenic properties. In healthy eumenorrheic women, it was demonstrated that the monophasic estroprogestin formulation containing CMA (2 mg) plus ethinyl estradiol (EE) (30 mcg) (EE30+CMA) is efficacious both in reducing hyperandrogenic symptoms, fat mass and in improving lipoprotein panel, without changes in insulin-glucose metabolism. These metabolic properties are important for women affected by polycystic ovary syndrome (PCOS) in whom there is a predisposition to insulin resistance. STUDY DESIGN: We studied whether in young nonobese women with PCOS (15 subjects, EE30+CMA-PCOS group) a six-cycle treatment with EE30+CMA can reduce androgen levels, androgen bioavailability and the score of hirsutism and acne, and modify glucose-insulin metabolism evaluated by the oral glucose tolerance test and the body composition evaluated by bio-impedenziometry. These parameters were evaluated before (first visit) and during the sixth cycle of EE30+CMA (second visit). All the results were compared with those of a matched-age-group of nonobese PCOS women (15 subjects, no OC-PCOS group) evaluated before (first visit) and after six menstrual cycles in which they did not use any drug or oral contraceptive (second visit). RESULTS: In the EE30+CMA-PCOS group women, androgen levels and bioavailability, hirsutism and acne score were significantly lower at the second than at the first visit, whereas they did not change in no OC-PCOS group. At the second visit, in both groups, glucose-insulin metabolism and body composition parameters were not affected. CONCLUSIONS: A six-cycle treatment with EE30+CMA is efficacious in nonobese PCOS women to improve hyperandrogenic symptoms, without negative interferences both on body composition and on insulin-glucose metabolism.

Evidence that in healthy young women, a six-cycle treatment with oral contraceptive containing 30 mcg of ethinylestradiol plus 2 mg of chlormadinone acetate reduces fat mass.

BACKGROUND: We aimed to evaluate whether a six-cycle treatment with oral contraceptive containing 30 mcg of ethinylestradiol (EE2) plus 2 mg of chlormadinone acetate (CMA) (EE2+CMA) alters body weight (BW) and body composition of healthy young women with normal menstrual cycles. The results in treated subjects were compared to those obtained in nontreated women as control. STUDY DESIGN: Multifrequency bioelectrical impedance analysis (MF-BIA) was performed in 48 healthy young women during the follicular phase of their menstrual cycle. Of this group, 24 women were treated with EE2+CMA, and the MF-BIA was repeated at the third and sixth cycle of treatment. The remaining 24 women were submitted to the same examinations after three and six cycles without any treatment. Total body water (TBW), intracellular water (ICW), extracellular water (ECW), fat mass (FM) and fat-free mass (FFM) were calculated. Waist-to-hip ratio (WHR), BW, blood pressure, and the plasma concentrations of electrolytes were also measured at each visit. RESULTS: Mean FM significantly (p<.05) decreased in the EE2+CMA group from basal levels of 14.23+/-1.03 to 13.51+/-1.09 and 12.71+/-1.02 kg at the third and sixth cycle of treatment, respectively. Stable values were seen in the control group. During observation, other parameters (BW, WHR, TBW, ECW, ICW, FFM) remained unchanged in all subjects. CONCLUSIONS: EE2+CMA reduces FM without altering TBW, ICW, ECW. These preliminary results suggest that progestational activity of CMA could balance both fluid retention and weight gain elicited by EE2.

Autoimmunity in gestational diabetes mellitus in Sardinia: a preliminary case-control report.

BACKGROUND: We previously reported a high prevalence (22.3%) of gestational diabetes mellitus (GDM) in a large group of Sardinian women, in contrast with the prevalence of Type 2 diabetes. Sardinia has an unusual distribution of haplotypes and genotypes, with the highest population frequency of HLA DR3 in the world, and after Finland, the highest prevalence of Type 1 diabetes and Autoimmune-related Diseases. In this study we preliminarily tested the prevalence of serological markers of Type 1 diabetes in a group of Sardinian GDM patients. METHODS: We determined glutamic decarboxylase antibodies (anti-GAD65), protein tyrosine phosphatase ICA 512 (IA2) antibodies (anti-IA2), and IAA in 62 GDM patients, and in 56 controls with matching age, gestational age and parity. RESULTS: We found a high prevalence and very unusual distribution of antibodies in GDM patients (38.8%), the anti-IA2 being the most frequent antibody. Out of all our GDM patients, 38.8% (24 of 62) were positive for at least one antibody. Anti-IA2 was present in 29.0 % (18 out of 62) vs. 7.1% (4 out of 56) in the controls (P < 0.001). IAA was present in 14.5% (9 out of 62) of our GDM patients, and absent in the control subjects (P < 0.001). Anti-GAD65 was also present in GDM patients, with a prevalence of 3.2% (2 out of 62) while it was absent in the control group (P = NS). Pre-gestational weight was significantly lower (57.78 +/- 9.8 vs 65.9 +/- 17.3 P = 0.04) in auto-antibodies- positive GDM patients. CONCLUSION: These results are in contrast with the very low prevalence of all antibodies reported in Italy. If confirmed, they could indicate that a large proportion of GDM patients in Sardinia have an autoimmune origin, in accordance with the high prevalence of Type 1 diabetes.

Reduced serum level of THDOC, an anticonvulsant steroid, in women with perimenstrual catamenial epilepsy.

PURPOSE: Seizure exacerbation in catamenial epilepsy (CE) is associated with the decrease in progesterone secretion and increase in estradiol secretion during the premenstrual period. Moreover, experimental evidence suggests that tetrahydrodeoxycorticosterone (THDOC), a positive modulator of the type A receptor for gamma-aminobutyric acid (GABA), and dehydroepiandrosterone sulfate (DHEAS), a negative modulator of this receptor, might play a crucial role in modulating seizure frequency during the menstrual cycle. Following these studies it seems of interest to investigate possible variations, among other hormonal parameters, of THDOC and DHEAS in CE patients. METHODS: The serum concentrations of progesterone (P4), pregnenolone, allopregnanolone (AP), THDOC, DHEAS, cortisol, and DHEAS/cortisol ratio were measured throughout the menstrual cycle at the 7th, 11th, 15th, 19th, 23rd, and 27th day from the onset of spontaneous menstrual blood loss in young premenopausal women with CE (n = 17) and age-matched controls (n = 13). RESULTS: At each time of the study, the serum concentration of THDOC and the DHEAS/cortisol ratio were lower (p < 0.05) in women with CE than in control women. The concentrations of P4, pregnenolone, and AP did not differ between the two groups of subjects. CONCLUSIONS: The reduced serum concentration of THDOC and the reduced DHEAS/cortisol ratio detected throughout the menstrual cycle in women with CE might play a role in CE. Moreover, the peculiar pattern of CE seizure exacerbation might suggest that these neuroendocrine variations are worth investigating in other epileptic syndromes, particularly in those characterized by relevant and uncontrolled variations in seizure frequency.

The oral contraceptive containing 30 microg of ethinylestradiol plus 3 mg of drospirenone is able to antagonize the increase of extracellular water occurring in healthy young women during the luteal phase of the menstrual cycle: an observational study.

PURPOSE: This nonrandomized study aimed to evaluate body weight and composition during the menstrual cycle and during oral contraception with 30 microg of ethinylestradiol plus 3 mg of drospirenone (EE+DRSP). DESIGN: Multifrequency bioelectrical impedance analysis was carried out in 38 normally cycling women (mean age, 25.5 years) at baseline during the follicular phase (FP) and the luteal phase (LP) of the menstrual cycle and after three and six cycles of EE+DRSP to evaluate total body water (TBW), intracellular water (ICW), extracellular water (ECW), fat mass and fat-free mass. Body weight, waist-to-hip ratio, blood pressure and the plasma concentrations of electrolytes were also determined at each visit. RESULTS: TBW and ECW increased in the LP. During EE+DRSP, TBW and ECW were significantly lower than in the LP but similar to the values measured in the FP. No significant variations in ICW or in the other parameters were observed. CONCLUSION: EE+DRSP maintains the same concentrations in TBW and ECW observed in the FP. This effect is likely due to the antimineralocorticoid activity of DRSP, which counteracts the water retention elicited by estrogen.

Efficacy of intravenous tramadol treatment for reducing pain during office diagnostic hysteroscopy.

OBJECTIVE: To assess whether IV tramadol before outpatient hysteroscopy could reduce procedure-related pain. DESIGN: A randomized double-blind placebo controlled trial. SETTING: Outpatient Hysteroscopy Centre in the Department of Obstetrics and Gynaecology of Cagliari University. PATIENT(S): Fifty healthy, parous, women who underwent outpatient diagnostic hysteroscopy and endometrial biopsy. INTERVENTION(S): Random IV infusion of tramadol or placebo before hysteroscopy and endometrial biopsy were performed. MAIN OUTCOME MEASURE(S): Visual analogue scale of pain was measured both immediately after and 15 minutes after the procedure. Stress hormones (ACTH, cortisol), blood pressure, and heart frequency were evaluated before, during, and 15 minutes after the procedure. RESULT(S): In the tramadol group, the visual analogue scale of pain was significantly lower than in the placebo group both immediately after the procedure and 15 minutes later. Basal levels of ACTH and cortisol did not differ between the groups. In both groups, the ACTH levels remained unchanged during the study, and the cortisol levels were higher 15 minutes after the procedure than before the procedure. Procedure time, heart frequency, blood pressure, and adverse effects did not differ between the groups. CONCLUSION(S): In parous women without uterine malformations, a treatment with tramadol before hysteroscopy and endometrial biopsy appears to be capable of reducing the pain and discomfort that are associated with this procedure.

Observational study on the stability of the psychological status during normal pregnancy and increased blood levels of neuroactive steroids with GABA-A receptor agonist activity.

We investigated whether pregnancy could modify psychological symptoms and whether neuroactive steroids which exert an anti-anxiety effect by acting on the gamma-aminobutyric acid (GABA)-A receptors, are modified during pregnancy in young healthy women. Healthy volunteer women in the Department of Obstetrics and Gynecology at Cagliari University participated in the study. They were divided into women with low (group 1, seven subjects) and high (group 2, seven subjects) psychological score by SCL-90 psychometric scale. Age, body mass index and physiological status of pregnancy did not differ between the groups. The subjects were studied before pregnancy during the follicular phase (FP), and the luteal phase (LP) of the menstrual cycle (MC) and four times during pregnancy (at 14th, 22nd, 30th, and 38th week). SCL-90 psychometric scale, circulating levels of progesterone (P4), 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone, AP), 3alpha,21-dihydroxy-5alpha-pregnan-20-one (allotetrahydrodeoxy-corticosterone, THDOC), cortisol and DHEAS were assayed at each visit. The SCL-90 global score and the intensity of psychological symptoms differ between the groups, but within each group they did not change both during MC and during pregnancy. The DHEAS and cortisol levels did not differ between the groups. DHEAS did not change during the study, whereas cortisol levels increased during pregnancy in both groups. Progesterone, AP, and THDOC levels were higher during LP than during FP and further increased during pregnancy, without any difference between the groups. In conclusion, pregnancy does not seem to interfere with the psychological status of healthy women independently of the psychological basal score. Some neuroactive steroids with anxiolytic activity seem to increase during pregnancy depending on placental function. Their increase could represent some kind of protection against maternal anxiety and stress due to concerns about the pregnancy outcome.

Short-term variations in bone remodeling markers of an oral contraception formulation containing 3 mg of drospirenone plus 30 microg of ethinyl estradiol: observational study in young postadolescent women.

The clinical study of treated subjects and nontreated controls was made in healthy eumenorrheic young postadolescent women volunteers in the Department of Obstetrics and Gynaecology at Cagliari University, to investigate whether an oral contraceptive (OC) containing drospirenone (3 mg) plus ethinyl estradiol (30 microg) (DRSP+EE) can affect bone metabolism. Control group (n = 26) and OC group (n = 28) women did not differ in age, body mass index, waist-to-hip ratio and main outcome measures [urinary levels of deoxypyridinoline and pyridinoline, serum levels of osteocalcin, bone specific alkaline phosphatase (bSAP), total testosterone (total-T), sex hormone-binding globulin (SHBG), progesterone and bone mineral density (BMD) at the heel]. The control group was studied at the luteal phase (LP) during both the first and the sixth menstrual cycle; the OC group was studied during the first cycle at the LP, and on days 16-18 of the sixth cycle of DRSP+EE treatment. At the sixth cycle, in the control group, the main outcome measures did not change compared to baseline. In the OC group, deoxypyridinoline, pyridinoline, osteocalcin, bSAP, total-T and progesterone levels were reduced, whereas SHBG levels were increased. The BMD was unchanged compared to baseline. The results suggest that 6-month DRSP+EE treatment decreases bone turnover.

Psychological effect of the oral contraceptive formulation containing 3 mg of drospirenone plus 30 microg of ethinyl estradiol.

OBJECTIVE: To investigate in healthy eumenorrheic young women whether an oral contraceptive (OC) containing drospirenone (DRSP) (3 mg) + ethinyl estradiol (EE) (30 microg) (DRSP + EE) could modify psychological symptoms and whether it could modify steroids interfering with the gamma-aminobutyric acid (GABA)-A receptors. DESIGN: Clinical study of treated subjects and nontreated controls. SETTING: Healthy volunteers in the Department of Obstetrics and Gynecology at Cagliari University. PATIENT(S): Control group (n = 12) and OC group (n = 10) women with similar age, body mass index, and main outcome measures. INTERVENTION(S): The control group was studied during the first menstrual cycle at the follicular phase (FP) and at the luteal phase (LP) and during the third cycle at the LP; the OC group was studied during the first cycle, as described above, and on day 16-18 of the third cycle of treatment with DRSP + EE. MAIN OUTCOME MEASURE(S): Psychometric scale (SCL-90), DHEAS, P, allopregnanolone (AP), and allotetrahydrodeoxy-corticosterone (THDOC). RESULT(S): SCL-90 and DHEAS did not vary throughout the menstrual cycle. P, AP, and THDOC values were higher during the LP than the FP. At the third cycle, in the control group the main outcome measures were similar to those at LP. In the OC group, the SCL-90 global score, the intensity of anxiety and phobic anxiety, the levels of anxiolytic steroids (P, AP, THDOC) and the anxiety-inducing steroid DHEAS were reduced. CONCLUSION(S): The results suggest beneficial effects of DRSP + EE on psychological symptoms by decreasing DHEAS.

Observational study on the efficacy of tibolone in counteracting early carotid atherosclerotic lesions in postmenopausal women.

OBJECTIVE: To study whether tibolone affects lipid profile and diffused intima media thickness (IMT) of the common carotid arteries (CCA) in postmenopausal women (PMW). METHODS: Twenty-two PMW and 20 premenopausal women participated in the study. The PMW were randomly divided into 11 women who did not receive any treatment and 11 women who received tibolone (2.5 mg once a day). RESULTS: After 6 months the treated women had lipoprotein(a) (Lpa), total-cholesterol (total-C), and LDL-cholesterol (LDL-C) levels lower than before, while in the non-treated women Lpa was increased. The IMT of CCA was unmodified in the treated women, whereas it increased in non-treated women. CONCLUSIONS: This preliminary study suggests that a 6-month tibolone treatment could counteract the increase of the IMT of CCA observed in untreated PMW.

Pattern of bone markers during pregnancy and their changes after delivery.

OBJECTIVE: To investigate whether bone resorption markers change during pregnancy and lactation, and how they are correlated with human placental lactogen (hPL) and PRL. SUBJECTS: Young women before pregnancy, during pregnancy and during a 12-month post-delivery period (study group; n = 22); and age- and weight-matched normal cycling women (control group; n = 22) for a 20-month-period participated in the study. RESULTS: In the study group, women both during pregnancy (from the 8th up to the 38th week) and during a 6-month period of lactation, pyridinoline and deoxypyridinoline urinary levels were significantly higher than those of pre-pregnancy and control women. They returned to basal values at the 12th post-delivery month. During pregnancy there were early and late peak increases, at the 8th and 32nd week, respectively. At the 32nd, 34th, 36th and 38th week of pregnancy, pyridinoline and deoxypyridinoline urinary values were significantly correlated with hPL serum levels. CONCLUSIONS: During pregnancy the maternal bone resorption seems to vary critically at early and late stages. A complete reversal of these variations seems to occur after lactation. Further studies could evaluate if changes in placental function are capable of differently interfering with maternal bone resorption.

Raloxifene does not modify insulin sensitivity and glucose metabolism in postmenopausal women.

Insulin sensitivity (Si), glucose tolerance, and lipid metabolism were investigated in osteopenic postmenopausal women before and after 6 months of treatment with raloxifene (60 mg/d) or placebo. In a group of women (n = 34), glucose metabolism was evaluated by means of an oral glucose tolerance test (75 g). In another group of women (n = 24), Si and peripheral glucose utilization not dependent on insulin were evaluated by means of a frequently sampled iv glucose tolerance test associated with the minimal model method. No metabolic modification was observed in women receiving placebo. Raloxifene did not significantly modify high density lipoprotein-cholesterol and triglycerides, whereas it significantly decreased low density lipoprotein (LDL) cholesterol (4.84 +/- 0.34 mmol/liter vs. 3.83 +/- 0.49 mmol/liter; P = 0.014) and LDL/high density lipoprotein cholesterol ratio (3.21 +/- 0.31 mmol/liter vs. 2.46 +/- 0.44 mmol/liter; P = 0.012). Fasting levels and responses to the oral glucose tolerance test of glucose, insulin, C-peptide, and C-peptide/insulin were not modified by raloxifene. Similarly, raloxifene did not modify Si (4.22 +/- 4.1 vs. 5.13 +/- 1.75), or insulin (0.025 +/- 0.003 vs. 0.019 +/- 0.002). The present data show that in osteopenic postmenopausal women raloxifene reduces LDL levels but does not modify insulin sensitivity and glucose metabolism.

The antiandrogenic effect of flutamide improves uterine perfusion in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate whether, by blocking androgen action, flutamide can decrease and normalize vascular resistance in the uterine artery in patients with polycystic ovary syndrome (PCOS). DESIGN: Prospective and controlled study. SETTING: Endocrinological Centre of the Department of Obstetrics and Gynecology of the University of Cagliari, Italy. PATIENT(S): Twenty-two patients with PCOS were enrolled in the study and randomly assigned to one of the following two treatments for 3 months: oral administration of flutamide (250 mg twice daily) or placebo. INTERVENTION(S): Doppler flow measurement of the uterine artery and serum hormone concentration determination during the early follicular phase of the menstrual cycle before treatment and during the third month of treatment. MAIN OUTCOME MEASURE(S): Pulsatility index (PI) of the uterine artery before and during treatment. RESULT(S): The PI of the uterine artery decreased significantly during treatment. No difference was found in patients treated with placebo. Correlation was found only between the PI values of the uterine artery and DHEAS. CONCLUSION(S): The low uterine perfusion that characterizes patients with PCOS can be improved by the antiandrogenic effect of flutamide.

Efficacy and safety of oral and transdermal hormonal replacement treatment containing levonorgestrel.

OBJECTIVES: The oral combined formulation of levonorgestrel with estradiol valerate (LNG+EV) has demonstrated to be effective on some postmenopausal symptoms. The availability of a transdermal HRT in sequential formulation with 17-beta-estradiol plus levonorgestrel (TSE2+TSLNG) induced us to do this control-study with the aim to evaluate the efficacy and safety of both oral and transdermal treatments. METHODS: At baseline, the psychological symptoms with the psychometric scale SCL-90, the bone resorption with the measurement of the urinary levels of pyridinoline and dexoxypirydinoline, and the insulin and lipid metabolism were assessed in 30 postmenopausal women (PMW) and in 18 premenopausal women. Then, the PMW women were randomly divided in three groups: group A (N=10) assumed EV+LNG, group B (N=10) did not assume any treatment, group C (N=10) was treated with TSE2+TSLNG. The length of the study was 12 months. The aforementioned assessments were repeated at different time-intervals up to the end of the study. RESULTS: The total score of SCL-90, the bone resorption, the levels of LDL-cholesterol, total-cholesterol and the parameters of insulin metabolism were higher in PMW than in premenopausal women. During the study, the SCL-90, the bone resorption, total-cholesterol, and LDL-cholesterol levels significantly decreased only in the groups A and C. By contrast, in the group B bone resorption significantly increased at the 12th month. During the treatments, insulin metabolism did not change in the groups A and B. In the group C the secretion of C-peptide and the C-peptide:insulin ratio after OGTT were significantly higher at the 12th month than before treatment. In all groups the endometrium thickness did not change during the study. CONCLUSION: A 12-month of either oral or transdermal HRT containing levonorgestrel seems to exert beneficial effects on the main postmenopausal symptoms without negative interferences on the endometrium.