Ultrasonographic soft markers for detection of rectosigmoid deep endometriosis.

OBJECTIVES: The aim of this study was to evaluate the use of ultrasound (US) soft markers as a first-line imaging tool to raise suspicion of rectosigmoid (RS) involvement in women suspected of having deep endometriosis. METHODS: We included in this prospective observational study all patients with clinical suspicion of deep endometriosis who underwent diagnostic transvaginal US evaluation at our unit from January 2016 to February 2017. Several US soft markers were evaluated for prediction of RS involvement (presence of US signs of uterine adenomyosis, presence of an endometrioma, adhesion of the ovary to the uterus (reduced ovarian mobility), presence of 'kissing ovaries' (KO) and absence of the 'sliding sign'), using as the gold standard expert US examination for the presence of RS endometriosis. RESULTS: Included were 333 patients with clinical suspicion of deep endometriosis. Of these, 106 had an US diagnosis of RS endometriosis by an expert. The only significant variables found in the prediction model were absence of the sliding sign (odds ratio (OR), 13.95; 95% CI, 7.7-25.3), presence of KO (OR, 22.5; 95% CI, 4.1-124.0) and the interaction between these two variables (OR, 0.03; 95% CI, 0.004-0.28). Regarding their interaction, RS endometriosis was present when KO was absent and the sliding sign was present in 10% (19/190) of cases, when both KO and the sliding sign were present in 71.4% (5/7) of cases, when both KO and the sliding sign were absent in 60.8% (76/125) of cases and when KO was present and the sliding sign was absent in 54.5% (6/11) of cases. Thus, when the sliding sign was absent and/or KO was present, transvaginal US showed a specificity of 75% (95% CI, 69-80%) and a sensitivity of 82% (95% CI, 73-88%). CONCLUSIONS: US findings of absence of the sliding sign and/or presence of KO in patients with clinical suspicion of endometriosis should raise suspicion of RS involvement and indicate referral for expert US examination, with a low rate of false-negative diagnosis. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Contraception during Coronavirus-Covid 19 pandemia. Recommendations of the Board of the Italian Society of Contraception.

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 pandemiaMaterials 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.

Monurelle Biogel® vaginal gel in the treatment of vaginal dryness in postmenopausal women.

OBJECTIVES: To evaluate efficacy, tolerability and safety of Monurelle Biogel® vaginal gel for treatment of vaginal dryness. METHODS: Multicenter, national, randomized, controlled vs. no-treatment, open-label study. Ninety-five postmenopausal women were randomized (48 to Monurelle Biogel® and 47 to no treatment). Primary endpoint was the change of Verbal Rating Scale (VRS) total score of vaginal atrophy (VA) symptoms after 8-week treatment. The main secondary endpoints were VRS single-item score, Vaginal Health Index (VHI) score, Maturation Index (MI), Female Sexual Function Index (FSFI), and Female Sexual Distress Scale-Revised (FSDS-R). RESULTS: The VRS total score was statistically significant in favor of the treatment group on day 28 (p = 0.001) but not on day 56 (p = 0.064). By excluding women who were not sexually active, the total VRS scores reached the criteria for clinical success in 27/43 subjects (62.8%) in the control arm and in 38/46 subjects (82.6%) in the treatment arm (p = 0.035) on day 56. The VHI score significantly changed in the active arm (4.71 ± 4.85 vs. 0.28 ± 1.71) (p < 0.001) on day 56. Even the MI significantly improved, with an increase in the percentage of superficial cells (p = 0.01). The improvements in both VHI and MI were still present at the follow-up visit after the discontinuation of the treatment (day 84). Sexual function and distress showed a statistical significant difference on day 56. CONCLUSIONS: Monurelle Biogel® vaginal gel applied twice daily for 8 weeks is effective in relieving vaginal dryness and other VA symptoms. Such a clinical meaningful effect persists at least 4 weeks and is supported by an improvement in the vaginal environment. Trial Registration clinicaltrials.gov Identifier: NCT02994342.

Soy isoflavones, inulin, calcium, and vitamin D3 in post-menopausal hot flushes: an observational study.

PURPOSE OF INVESTIGATION: To evaluate the effect of soy isoflavones and inulin (SII) on hot flushes (HF) and quality of life in a clinical setting, the authors conducted an observational study. MATERIALS AND METHODS: The authors performed an observational, prospective, multicentric study on women in peri-/post-menopause treated or untreated with a product present on the Italian market, consisting in a mixture of calcium (500 mg), vitamin D3 (300 IU), inulin (3 g) and soy isoflavones (40 mg). RESULTS: A total of 135 patients, 75 (55.6%) in the SII group and 60 (44.4%) in the untreated group entered the study. After three months, the mean number of HF declined of 2.8 (SD 3.7) in the SII group and 0.0 in the untreated one. The corresponding values after six months were -3.7 (SD 2.7) in the SII group and -0.9 (SD 5.3) in the control group (p = 0.02). CONCLUSION: This observational trial suggests a possible beneficial effect of a dietary soy supplement containing 40 mg of isoflavone/day plus inulin in the management of menopausal symptoms such as hot flashes.

[Short-term effect of an estroprogestin containing ethinylestradiol 20 mcg + drospirenone 3 mg in 24+4 regimen at hormonal and cutaneous level in ovarian hyperandrogenism]. / Effecto a breve termine di un estroprogestinico contenente etinilestradiolo 20 mcg+drospirenone 3mg in schema 24 + 4 a livello ormonale e cutaneo nell'iperandrogenismo ovarico.

AIM: evaluate the efficacy of an estroprogestin EP containing 20 mcg ethinilestradiol (EE) and 3 mg drospirenone (DRSP) in the treatment of hyperandrogenism. METHODS: In this study, twenty hyperandrogenic patients were treated with an EP containing EE 20 mcg and DRSP 3 mg in 24+4 regimen for three months. Skin evaluation was performed both quantitatively and qualitatively. RESULTS AND CONCLUSION: This EP combination showed, after a short-term treatment (three months) to decrease significantly seborrhea, acne, and circulating androgens (testosterone, deidroepiandrosterone sulphate, and androstenedione), while increased sex hormone binding globulin levels. Moreover, this EE 20 mcg/DRSP 3mg EP combination changed some parameters of skin quality, increasing corneometry (a parameter related to skin hydration), and reduced trans epidermal water loss (TEWL, a parameter related to skin evaporation), and erythema (a parameter related to skin inflammation). These results could be taken into account in individualizing the treatment of hyperandrogenic patients.

Reply to the 'Comment on "Metal-organic green dye: chemical and physical insight into a modified Zn-benzoporphyrin for dye-sensitized solar cells"' by R. Steer, RSC Advances, 2018, DOI: 10.1039/c8ra00213d.

The authors reply to the comment by R. P. Steer discussing the reasons for their incorrect assignment of the luminescence decay of the novel compound 5,10,15-(triphenyl),20-[ethynyl-(4-carboxy)phenyl]tetrabenzoporphyrinate Zn(ii) (PETBP). Further DFT and TDDFT calculations have been performed on the compound to investigate the possibility of a direct S2-S0 decay instead of a S2-S1 conversion with a subsequent emission to the ground state. In addition, the presence of traces of very luminescent contaminants of the ring-opened type has been considered on the grounds of calculated absorption and fluorescence spectra. The results of these investigations confirm that the S2-S0 emission reported in the commented paper is not attributable to the target molecule but rather to a neglected luminescent impurity.

Prolonged opioid blockade does not influence luteinizing hormone modifications of the follicular and luteal menstrual phases.

Although an acute opioid withdrawal markedly modifies LH secretion in the different phases of the menstrual cycle, whether a sustained opioid blockade imbalances spontaneous LH modifications associated with the progression of the follicular or luteal menstrual phases is presently unknown. Accordingly, normal cycling women during either the follicular (n = 14) or luteal (n = 14) menstrual phase, randomly and in double blind fashion, received either placebo (n = 7 for each phase) or 50 mg/day of the oral opioid antagonist naltrexone (n = 7 for each phase). In each subject, LH pulsatility (10-min blood drawing for 8 h) and the pituitary LH response to a 10-micrograms GnRH stimulus were investigated at baseline and on the fifth day of placebo/naltrexone administration. In the follicular phase, after placebo treatment, the number and amplitude of LH pulses did not significantly vary, whereas mean LH levels (P < 0.01) and the LH response to GnRH (P < 0.05) were significantly increased. The same occurred after naltrexone treatment, when significant increases in both mean LH levels (P < 0.02) and LH response to GnRH (P < 0.025) were observed. In the luteal phase, after placebo administration, the frequency of LH pulses and mean LH levels were not modified, but both the amplitude of LH pulses (P < 0.025) and the LH response to GnRH were reduced (P < 0.02). The same occurred after naltrexone treatment, when significant decreases in both the amplitude of LH pulses (P < 0.05) and the LH response to GnRH (P < 0.05) were observed. During both phases of the menstrual cycle, the modifications observed during naltrexone treatment were similar and not significantly different from those observed during placebo. The present data do not support important modulatory functions for endogenous opioid peptides on spontaneous LH modifications occurring with the progression of the follicular or the luteal menstrual phases.

Melatonin enhances the luteinizing hormone and follicle-stimulating hormone responses to gonadotropin-releasing hormone in the follicular, but not in the luteal, menstrual phase.

Exogenous melatonin enhances LH pulse amplitude and mean LH levels in women during the follicular, but not the luteal, menstrual phase. In this study we investigated whether an increased pituitary response to GnRH is involved in the stimulatory effect of melatonin. Eight normal cycling women were studied on 2 consecutive days during the follicular stage (days 4-6), and eight were studied during the luteal phase (days 19-21) of the menstrual cycle. On 2 consecutive days, each women received, randomly and in a double blind fashion, placebo or 3 mg melatonin (1 mg at 0800, 1000, and 1200 h), whereas the pituitary LH and FSH responses to GnRH were tested by the iv administration of three submaximal doses of GnRH (1 microgram at 0900 h, 5 micrograms at 1100 h, and 10 micrograms at 1300 h). In the follicular phase, melatonin administration enhanced the LH and FSH responses to all three GnRH stimuli, whereas in the luteal phase, melatonin administration was ineffective. The present data indicate that an enhancing effect of melatonin on the LH and FSH responses to submaximal GnRH stimuli is evident in the follicular, but not the luteal, phase of the menstrual cycle and infer an endocrine window for the effect of melatonin on gonadotropin secretion.

Glucose metabolism and insulin resistance in women with polycystic ovary syndrome during therapy with oral contraceptives containing cyproterone acetate or desogestrel.

Oral contraceptives slightly deteriorate insulin sensitivity. The present study investigated whether they may further unbalance the glucose metabolism of lean women with polycystic ovary syndrome (PCOS). Women with PCOS were assigned to receive for 6 months the biphasic association of 40/30 micro g ethinyl estradiol (EE) and 25/125 micro g desogestrel (DSG; n = 10) or the monophasic association of 35 micro g EE and 2 mg cyproterone acetate (CPA; n = 10). Glucose tolerance was investigated by an oral glucose tolerance test (OGTT). Glucose utilization dependent [insulin sensitivity (SI)] or independent (Sg) of insulin was investigated by the minimal model method applied to a frequently sampled iv glucose tolerance test. EE/DSG increased the response of C peptide to OGTT (1413 +/- 113 vs. 2053 +/- 213 area under the curve; P < 0.009) and the C peptide/insulin ratio (0.085 +/- 0.01 vs. 0.134 +/- 0.01 area under the curve; P < 0.003). It also increased the Sg (0.026 +/- 0.002 vs. 0.034 +/- 0.003; P < 0.04) and decreased the SI (2.40 +/- 0.26 vs. 1.68 +/- 0.27; P < 0.01). EE/CPA did not modify responses to OGTT of glucose, insulin, C peptide, or C peptide/insulin ratio. It did not modify Sg and significantly increased SI (1.47 +/- 0.38 vs. 3.27 +/- 0.48; P < 0.04). The present study indicates that EE/CPA improves SI, whereas EE/DSG impairs SI, but improves insulin clearance. The long-term metabolic effects of these two compounds on women with PCOS require further investigations.

Effects of low doses of transdermal 17 beta-estradiol on carbohydrate metabolism in postmenopausal women.

The impact of a 3-month continuous administration of transdermal estradiol (E2-TTS 50; 50 micrograms/day) or oral conjugated estrogen (CE; 0.625 mg/day) on glucose and lipid metabolism was investigated in two groups (n = 15/group) of postmenopausal women. Fasting levels of glucose, insulin, and C-peptide; C-peptide/insulin ratio (index of hepatic insulin clearance); and their responses to a 75-g oral glucose tolerance test (OGTT) were evaluated before and after 3 months of continuous estrogen administration. E2-TTS 50 modified carbohydrate metabolism, decreasing fasting insulin levels (P less than 0.01) and increasing the pancreatic islet response to glucose challenges, as indicated by an increased integrated value of the C-peptide curve associated with OGTT (P less than 0.05). Despite greater C-peptide secretion, integrated peripheral insulin after OGTT was decreased (P less than 0.05). The resulting increase in the integrated curve of the molar C-peptide/insulin ratio (P less than 0.01) indicated elevated hepatic insulin clearance after E2-TTS 50 administration. CE treatment did not modify carbohydrate metabolism, except for reducing fasting glucose levels (P less than 0.01). Neither therapy modified lipid metabolism, but a slight increase in circulating triglycerides (P less than 0.01) was observed during CE administration. Our data show that the addition of low doses of natural estrogens does not negatively influence glucose and lipid metabolism in postmenopausal women. By contrast, reversal of postmenopausal hypoestrogenism to early follicular phase estrogenic values with E2-TTS 50 administration seems to exert a beneficial effect on glucose metabolism by increasing hepatic insulin clearance.

Restoration of luteinizing hormone response to naloxone in postmenopausal women by chronic administration of the antidopaminergic drug veralipride.

To determine whether antidopaminergic drug administration may modify endogenous opioid activity at the hypothalamic-pituitary level, the effects of naloxone infusion (1.6 mg/h for 4 h) on LH secretion were studied in six postmenopausal women before and after administration of the potent antidopaminergic drug veralipride for 20 days. Before veralipride administration, the naloxone infusion did not alter LH secretion. Chronic administration of veralipride resulted in a significant (P less than 0.01) decline in plasma LH levels. In addition, the naloxone infusion induced a significant (P less than 0.05) increase in plasma LH levels, which reached values similar to those before veralipride administration. These results demonstrate that in postmenopausal women the antidopaminergic drug veralipride can restore, at least in part, the activity of the endogenous opioid system. These findings suggest that endogenous opioid peptides may mediate the inhibitory effect exerted by chronic antidopaminergic drug administration on LH secretion in humans.

Dose-related prolactin inhibitory effect of the new long-acting dopamine receptor agonist cabergoline in normal cycling, puerperal, and hyperprolactinemic women.

Two different single doses (400 and 600 micrograms) of the new long-acting dopamine agonist cabergoline (CBG) were given to 12 normal cycling women, 17 puerperal women, and 24 hyperprolactinemic women (12 with idiopathic hyperprolactinemia and 12 with pituitary adenoma). Plasma PRL was determined in blood samples collected before and at frequent intervals for 5 days after CBG administration. Both CBG doses induced marked inhibition of PRL secretion in all women. A decrease in plasma PRL levels was evident 1-2 h after CBG administration and persisted for up to 5 days. The 600-micrograms CBG dose had a more potent (P less than 0.05) PRL inhibitory effect than the 400-micrograms dose in normal, puerperal, and hyperprolactinemic women. Moreover, while 400 micrograms CBG prevented lactation in 3 of 7 puerperal women, 600 micrograms CBG prevented lactation in 5 of 5 puerperal women. A moderate blood pressure decrease occurred 3-6 h after CBG treatment, but no other side-effects occurred. These results demonstrate that CBG induces a dose-related inhibition of PRL secretion in normal women as well as in puerperal and hyperprolactinemic women. The potent long-lasting PRL inhibitory effect of CBG in conjunction with the absence of side-effects typical of dopaminergic compounds suggest that this drug is an advance in the medical treatment of hyperprolactinemia.

Effects of transdermal 17 beta-estradiol treatment and naloxone infusion on gonadotropin response to gonadotropin-releasing hormone in postmenopausal women.

Estrogens exert both inhibitory and stimulatory effects on the secretion of GnRH and gonadotropins in women. The endogenous opioid peptides seem to mediate, at least in part, the inhibitory action exerted by estrogens on LH secretion. However, the mechanisms that mediate the stimulatory effect of estrogens on LH secretion are still unclear. The present study was performed to evaluate whether the endogenous opioid peptides could also participate in the stimulatory effect that estrogens exert on the gonadotropin response to GnRH. In postmenopausal women, a GnRH test was performed both under basal conditions and during the second month of treatment with transdermal 17 beta-estradiol (E2). In untreated postmenopausal women, two different doses of naloxone infusion failed to modify the LH and FSH responses to GnRH stimulation. During treatment with transdermal E2, the LH response to GnRH was significantly increased, while the FSH response was similar to that before treatment. Naloxone completely counteracted the enhanced LH response to GnRH observed during E2 treatment. On the other hand, naloxone did not significantly modify the FSH response to GnRH. The present results confirm that E2 exerts a sensitizing effect on the pituitary LH response to GnRH and suggest that the endogenous opioid system could be involved in this effect.

Dexamethasone reduces the postcastration gonadotropin rise in women.

To investigate the influence of glucocorticoids on gonadotropin release in humans, we studied the effects of dexamethasone (DXM) administration on basal and GnRH-stimulated gonadotropin secretion in normal women after bilateral ovariectomy (OVR). From the 7th to the 14th day after OVR, 9 women received DXM (2.25 mg/day) and 13 women received placebo (control women). Plasma FSH and LH concentrations were measured before OVR and daily from the 7th to the 14th day after surgery. In addition, the FSH and LH responses to exogenous GnRH (10 micrograms, iv bolus dose) were determined in all DXM-treated women and in 5 control women on the 7th and 14th days after surgery. Plasma gonadotropin levels increased similarly in all women on the 7th day after OVR. DXM administration significantly limited (P less than 0.001) the progressive rise of basal LH and FSH levels from days 7 to 14. DXM treatment also blunted (P less than 0.005) the OVR-induced increase in the responsiveness of both LH and FSH to exogenous GnRH. These findings suggest that glucocorticoids inhibit the secretion of both gonadotropins at the pituitary level in ovariectomized women.

High testosterone levels of ovarian origin affect adrenal steroidogenesis?

Androgens of ovarian origin have been suggested to affect adrenal enzymatic activity. To investigate this possibility, the 17-hydroxyprogesterone (17-OH P) and cortisol (F) responses to an ACTH stimulation test (0.25 mg iv, bolus) were evaluated in 10 normal women and in 39 hyperandrogenic women with normal (14 subjects) or high (25 subjects) testosterone (T) levels. The 17-OH P release and the ratio between 17-OH P and F release in response to the ACTH stimulation test were significantly higher (P less than 0.05) in hyperandrogenic women with high T levels than in normal subjects. Eight hyperandrogenic women with high T received intranasal GnRH agonist (Buserelin, 1200 micrograms/day) for 4 weeks, and the 17-OH P and F release in response to the ACTH stimulation was reassessed after agonist treatment. At the end of GnRH agonist administration the mean circulating levels of T were significantly reduced (P less than 0.05). The F response to the ACTH test was not modified by pretreatment with the GnRH agonist. The 17-OH P response to the ACTH stimulation test after the GnRH agonist was unchanged in comparison with control tests, as well as the ratio between 17-OH P and F responses to the ACTH test. These data do not seem to confirm, as previously suggested, that high T levels of ovarian origin affect adrenal steroidogenesis.

Inhibitory effect of the dopamine agonist bromocriptine on the postcastration gonadotrophin rise in women.

Basal or stimulated gonadotrophin plasma levels were measured after bilateral ovariectomy in untreated and bromocriptine (BCT)-treated normal women. BCT was orally administered from the 7th to the 14th day after ovariectomy at a dose of 3.75 mg/day. BCT significantly (P less than 0.05) inhibited LH release, both basally and after LRF stimulation. Plasma FSH levels were also reduced in treated subjects, but this decrease did not reach statistical significance relative to controls. The blunted postcastration gonadotrophin rise found with BCT administration suggests that pituitary gonadotropin secretion is, in part, under dopaminergic inhibitory control.

Evidence that cyproterone acetate improves psychological symptoms and enhances the activity of the dopaminergic system in postmenopause.

The psychological symptoms assessed with a validated psychometric scale, SCL-90, were significantly higher in postmenopausal women (PMW; 60 subjects) than in premenopausal women (20 subjects). In the same PMW, the activity of the dopaminergic system, assessed with the PRL response to the dopamine-blocking agent sulpiride, was significantly lower than that in premenopausal women. During a period of 12 weeks the 60 PMW were randomly divided into 3 groups: no treatment (group A; n = 20), treatment with estradiol (E(2)) alone (patches with a E(2) release of 50 microg/24 h; group B; n = 20), and treatment with hormonal replacement therapy [estradiol valerate (EV) at a daily dose of 2 mg for 11 days and EV at the same daily doses plus cyproterone acetate (CPA) at a daily dose of 1 mg/day for 10 days; group C; n = 20). At the 12th week of the observation, only in group C women were the psychological symptoms significantly decreased, and the indirect evaluation of the dopaminergic system activity through PRL response to sulpiride showed a significant increase. During the same period, no changes in testosterone levels were observed in any group of PMW, whereas a significant increase in E(2) levels was found in both groups B and C. Although it is likely that the improvement in psychological symptoms with EV and CPA was due to progestin, we cannot rule out the possibility that greater estrogen exposure may have played a role.

Gamma-amino-beta-hydroxy butyric acid stimulates prolactin and growth hormone release in normal women.

The influence of gamma-amino-beta-hydroxy butyric acid (GABOB) treatment on pituitary function has been investigated in this study. Different doses (50 x 100 mg) of GABOB were iv injected into three and six normal women, respectively. PRL and GH plasma levels were measured before and after the injection. The treatment with 150 mg GABOB, performed in another two normal women, was interrupted because of side-effects (loss of consciousness etc.) due to the treatment. The treatment with 50 mg GABOB did not induce significant variations of the two hormones; however, significant increases of PRL (P less than 0.05) and GH (P less than 0.01) plasma levels were observed after injection with 100 mg GABOB. The present data suggest that gamma-amino butyric acid (GABA) itself of GABAergic drugs might play an important role in the control of hypothalamic-pituitary function.

The effects of the gabaergic drug, sodium valproate, on prolactin secretion in normal and hyperprolactinemic subjects.

To find out whether the gamma-aminobutyric acid (GABA)ergic system affects PRL secretion in humans, sodium valproate (DPA or Na-dipropyl-acetate), a drug inducing increase of endogenous GABA, was administered to 20 normal and 15 hyperprolactinemic subjects. PRL circulating levels were measured by RIA in the samples obtained after acute oral treatment with 400 mg DPA. A significant decrease (P less than 0.01) in comparison with basal levels was observed in normal women from 30-180 min after drug administration. DPA treatment also lowered blood PRL levels in hyperprolactinemic subjects (seven females) without evidence of pituitary tumor. A decrease very similar to the one found in normal subjects (P less than 0.05 vs. basal levels) was observed within 180 min from drug ingestion. Conversely, no significant changes were found after the same treatment in hyperprolactinemic patients with evidence of prolactinoma (seven females and one male). Taken together, these data seem to demonstrate that pharmacological enhancement of endogenous GABAergic tone is followed by inhibition of PRL secretion. They also suggest that GABA may exert an inhibitory control on PRL release in humans. In hyperprolactinemic subjects, this GABAergic control appears to be present only when a pituitary tumor cannot be demonstrated.