Impact of vulvovaginal atrophy of menopause: prevalence and symptoms in Italian women according to the EVES study

Abstract

This cross-sectional study included postmenopausal women, aged 45–75?years, with the aim to assess the presence of vulvovaginal atrophy (VVA) confirmed by a clinical assessment in the Italian population attending menopausal/gynecological centers. Apart from baseline variables, women scored vaginal, vulvar and urinary VVA symptoms. Impact of VVA on sexual function and quality of life (QoL) was assessed thorough EuroQoL questionnaire (EQ5D3L), Day-to-Day Impact of Vaginal Aging (DIVA), Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-revised (FSDS-R). A physical examination was carried out in accordance with routine gynecological practice. VVA was confirmed in 90% of the 1226 evaluable patients (aged 59.0?±?7.3?years). The prevalence of postmenopausal women with VVA confirmed by gynecological clinical assessment was 75.3%. The patients with VVA confirmed (n?=?926) had more severe symptoms (p?<?.0005), lower QoL (EQ-visual analog scale, p?=?.008 and DIVA, p?<?.0005) and worsened sexual function (FSFI and FSDS-R, p?<?.0005 for both) when compared with the patients having nonconfirmed VVA (n?=?140). VVA is highly prevalent among postmenopausal Italian women. The objective of VVA confirmation is associated with severe symptoms and impaired QoL and sexual function. A proactive approach of Italian clinicians to promote regular and early gynecological evaluation should be performed in order to delay the advancing of the disorder.     

Insulin sensitivity in women: a comparison among values derived from intravenous glucose tolerance tests with different sampling frequency, oral glucose tolerance test or fasting

OBJECTIVE: To determine the correlation between insulin sensitivity (S(I)) obtained by the minimal model method applied to a frequently sampled (n=33) intravenous glucose tolerance test (FSIGT(33)), and values obtained by reduced FSIGTs, oral glucose tolerance test (OGTT), or fasting. DESIGN: Retrospective analysis on tests performed in prospective studies. METHODS: A total of 78 FSIGT(33), and 59 OGTT were performed in non-diabetic women of which 10 were young cyclic females in the early follicular menstrual phase, 10 were young non-obese subjects with polycystic ovary syndrome (PCOS) and 30 were in post-menopause. Some of these individuals were investigated both prior to and during specified treatments. FSIGT(33) was transformed into FSIGT(22) and FSIGT(12) by removing samples from the analysis. Values of SI derived from reduced FSIGTs or calculations performed on glucose and insulin values observed in fasting conditions and/or during OGTT were related to those of FSIGT(33). RESULTS: S(I) values derived from FSIGT(33) were highly correlated with those derived from FSIGT(22) (r=0.965) or FSIGT(12) (r=0.955), but were only weakly correlated with those derived from fasting or OGTT calculations (r below 0.5). Between-group (PCOS vs normal) or within-group (prior to and during treatment) comparisons showed that reduced FSIGTs were only slightly less powerful than FSIGT(33) in detecting differences in S(I). CONCLUSIONS: In non-diabetic women, reduced FSIGTs but not calculations based on fasting or OGTT values may be used in place of FSIGT(33) to document S(I) and its variation.     

Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy

OBJECTIVE: Several effects of melatonin are modulated by gonadal steroids and are reduced in ageing women. Administration of melatonin reduces internal carotid artery pulsatility index (PI), and blood pressure in young individuals. Whether these effects are conserved in postmenopausal women and are influenced by hormone replacement therapy (HRT), was herein investigated. DESIGN: Randomised, double-blind placebo controlled study. PATIENTS: Twenty-three postmenopausal women of which 11 were unreplaced with HRT and 12 on the oestrogenic phase of continuous transdermal estradiol (50 microg/day) plus cyclic medroxyprogesterone acetate (5 mg/day x 12 days every 28 days). MEASUREMENTS: Internal carotid PI, by colour Doppler, and supine blood pressure were evaluated 90, 180 and 240 minutes following the oral administration of melatonin (1 mg) or placebo. Levels of nitrites/nitrates (NOx), the stable derivatives of nitric oxide, were also evaluated in samples collected 90 minutes following the administration of placebo or melatonin. RESULTS: In women not on replacement therapy melatonin was ineffective. In HRT-treated women, melatonin reduced internal carotid artery PI (P = 0.005). The effect was maximal within 90 minutes, and maintained for at least 240 minutes, with melatonin levels in the nocturnal physiological range. Systolic and diastolic blood pressures were reduced of 8 mmHg (P = 0.038) and 4 mmHg (P = 0.045), respectively, while NOx levels were significantly increased (P = 0.024). CONCLUSIONS: The circulatory response to melatonin is conserved in postmenopausal women with but not without hormone replacement therapy. Maintenance of the cardiovascular response to melatonin, may be implicated in the reduced cardiovascular risk of postmenopausal women with hormone replacement therapy.     

Effects of transdermal estrogen administration on peripheral vascular responsiveness in menopausal women

This study was designed to evaluate the peripheral vascular responses to acute estrogen replacement. According to a cross-over, double-blind study design, we randomized nine healthy postmenopausal women (time lapse from menopause to >1 year; mean age±SD 45.4±11.7 years) to treatment with transdermal patches of estradiol-17 or matched placebo. The estrogen patch was rated to assure a plasma concentration of substance of more than 100 pg/ml after 8–10 hours of treatment. Forearm blood flow (ml/100 ml/minute), local vascular resistance (mmHg/ml/100 ml/minute), venous volume (ml/100 ml), and venous compliance (ml/100 ml/mmHg) were measured in supine resting subjects by the straingauge venous occlusion plethysmography. Plasma concentration of norepinephrine (pg/ml) was quantified by HPLC-ED. Estradiol-17 produced increase in forearm blood flow and decrease in local vascular resistance. The drug reduced circulating norepinephrine concentrations. There were no significant changes in mean arterial pressure or heart rate. Venous volume and venous compliance were both enhanced by estrogen administration. The peripheral circulatory changes are attributed to a direct activity of estradiol-17 on arterial and venous wall and may in part reflect a modulation of estrogen on peripheral sympathetic tone.     

Effects of the antidopaminergic drug veralipride on LH and PRL secretion in postmenopausal women

Patterns of LH and PRL secretion have been evaluated in 15 postmenopausal women before and after the chronic blockage of the D2 dopamine receptors with veralipride (100 mg twice daily, for 30 days). In addition, the possible influence of the antidopaminergic drug on the activity of the endogenous opioid system has been evaluated by the infusion of the opioid antagonist naloxone, performed before and during veralipride administration. Mean plasma LH levels were significantly blunted (p less than 0.05) and mean plasma PRL levels were significantly increased (p less than 0.001) by veralipride administration. The frequency of both LH and PRL secretory pulses was not modified, while the mean pulse amplitude of both hormones was significantly increased (p less than 0.05 for LH; p less than 0.001 for PRL) by veralipride administration. In untreated postmenopausal women naloxone infusion did not modify LH secretion. Following veralipride, the infusion of naloxone significantly increased (p less than 0.05) the mean plasma LH levels, had no influence on the frequency and significantly reduced (p less than 0.01) the amplitude of LH pulses, expressed as the percent increase from the nadir to the peak. Both before and after veralipride administration, naloxone failed to modify the pattern of PRL secretion. In untreated postmenopausal women, the percentage of concomitant PRL and LH pulses was significantly higher (p less than 0.001) during naloxone than during saline infusion, and this effect was amplified by veralipride administration (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

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

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

A comparison of the central effects of different progestins used in hormone replacement therapy

Objective: To evaluate the central effect exerted by different progestins used for hormone replacement therapy. Methods: Randomised, placebo-controlled study. One hundred-twenty postmenopausal women on continuous hormonal replacement therapy with transdermal estradiol (50 μg per day) associated, for 10 days every 28 days, with four different progestins: dydrogesterone (DYD; 10 mg per day; n=20), medroxyprogesterone acetete (MPA; 10 mg per day; n=20), nomegestrol acetate (NMG; 5 mg per day; n=20) or norethisterone acetate (NETA; 10 mg per day; n=20). Other 40 women, 10 for each treatment group, were used as controls and were monitored for a single cycle of 28 days during the administration of transdermal estradiol plus placebo. Morning basal body temperature (BBT) was monitored for 28 days. Anxiety, by the state-trait anxiety inventory, and depression, by the self-evaluation depression scale of Zung, were evaluated just prior to and in the last 2 days of the 10-day progestins adjunct. Results: All progestins except DYD increased (P<0.0001) BBT by 0.3–0.5 °C. Anxiety was decreased by DYD (−2.3+1.1; P<0.01) and MPA (−1.5+0.5; P<0.01), but not by NMG or NETA. Depression did not significantly increase during progestins and actually decreased during MPA (−3.0+0.7; P<0.01). Only the effect of DYD on anxiety and that of MPA on depression were significant versus the control group (P<0.05). Conclusions: Different progestins exert different central effects. DYD has the peculiarity of not increasing BBT and of decreasing anxiety, which is also decreased by MPA. Depression is not negatively affected by the tested progestins and it may be ameliorated by MPA. The present data may help to individualise the progestin choice of hormone replacement therapy.     

Influences of maternal weight on the secondary sex ratio of human offspring

BACKGROUND: Less than optimal reproductive conditions may be associated with a secondary sex ratio biased towards females. Body weight represents a critical determinant of reproduction. Accordingly, we evaluated whether preconception body weight and weight gain during pregnancy influence the sex ratio of human offspring. METHODS: A retrospective study was performed on 10 239 births in 1997-2001. Time of conception, preconception body weight and net weight gain during pregnancy were obtained for 9284 pregnancies. RESULTS: The secondary sex ratio of mothers in the lowest quartile of pre-pregnancy body weight (<54.6 kg) was lower than that of the other three quartiles (0.497 versus 0.525; P < 0.01). In contrast, the sex ratio of children born by the women in the highest quartile of weight gain during pregnancy appeared lower than that of the first three quartiles (0.493 versus 0.516; P = 0.054). CONCLUSIONS: A low pre-pregnancy weight and a greater weight gain during pregnancy are both associated with a reduced secondary sex ratio. These data indicate that in women with non-optimal reproductive/metabolic conditions, a greater attrition is exerted on male than on female offspring.     

The male disadvantage and the seasonal rhythm of sex ratio at the time of conception

BACKGROUND: In accordance with a presumed greater fragility of male versus female pregnancies, we tested whether sex ratio (male/female ratio) of vital pregnancies is higher in seasons more favourable for reproduction. METHODS: A retrospective study was performed on 14,310 births which had occurred in our institute between 1995-2001. For each single pregnancy the time of conception was calculated by the last menstrual period recall and confirmed or redefined by ultrasound in 95.8% of cases. The sex ratio of 199,454 pregnancies which had occurred in the Modena County between 1936-1998 was also stratified according to the month of birth. RESULTS: Sex ratio of institutional deliveries was 0.511 and was identical to that obtained from the County registry. Sex ratio at birth did not show a significant seasonal variation. By contrast, sex ratio calculated at time of conception showed a seasonal rhythm, with amplitude of 2.4% and peak values in October (confidence interval: +/-43 days). The rhythm was in phase with the rhythm of conception that showed peak values in September (confidence interval: +/-37 days) and an amplitude of 7%. CONCLUSIONS: The superimposition of the phase of sex ratio and conception rhythms supports the contention that more males than females are conceived in seasons with more favourable reproductive conditions.     

Tibolone and estradiol plus norethisterone acetate similarly influence endothelium-dependent vasodilatation in healthy postmenopausal women

In healthy postmenopausal women, E(2) plus norethisterone acetate (1 mg + 0.5 mg) or tibolone (2.5 mg) similarly modify flow-mediated endothelium-dependent vasodilatation. The effect is dependent on baseline vasodilator reserve, with low values being augmented by either treatment.