Relation between body mass index and endothelium-dependent vasodilatation in healthy postmenopausal women.

OBJECTIVE: To evaluate whether endothelium-dependent vasodilatation is related to anthropometric parameters in 105 healthy postmenopausal women 47-68 years of age. METHODS: Flow-dependent, endothelium-dependent vasodilatation was considered as the maximal dilatation following deflation of a cuff placed on the forearm and inflated to supra-systolic blood pressure values for 4 min. Endothelium-independent vasodilatation was considered as the maximal dilatation induced by sublingual nitroglycerine (400 microg). RESULTS: Among parameters such as height, weight, body mass index (BMI), waist, hip, waist/hip ratio, lipids, glucose or insulin, only BMI, an indirect index of adiposity, was independently and directly related to baseline brachial artery diameter (b = 0.042, r = 0.269, p = 0.0055) and flow-mediated endothelium-dependent vasodilatation either expressed as net (b = 0.034, r = 0.315, p = 0.001) or percentage (b = 0.376, r = 0.202, p = 0.039) change. Stratification for BMI categories showed that women with BMI < 22 kg/m(2) had an endothelium-dependent vasodilatation, significantly lower than that of women with BMI >or= 30 kg/m(2) (0.711 +/- 0.076 mm vs. 1.107 +/- 0.141 mm; p = 0.0114). BMI was not related to endothelium-independent vasodilatation. CONCLUSIONS: Present results show that, in healthy postmenopausal women, endothelium-dependent vasodilatation is related to BMI, arteries of slender women dilating less than those of their heavier counterparts. A low BMI does not appear to be beneficial for artery vasodilatation in healthy postmenopausal women.

Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men.

In this study it was investigated whether the oral administration of melatonin (1 mg) in comparison to placebo was able to reduce blood pressure, vascular reactivity, and catecholamines in men, as previously reported in young women. The administration of melatonin significantly reduced blood pressure, the pulsatility index in the internal carotid artery, and catecholamines levels within 90 minutes. The effect of melatonin on the artery pulsatility index was related to baseline values, being greater in men with higher baseline values. The present data indicate that melatonin may blunt the activity of the cardiovascular system and may have both physiopathologic and clinical implications.

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.

Continuous combined hormone replacement therapy with oral 17beta-estradiol and norethisterone acetate improves homocysteine metabolism in postmenopausal women.

OBJECTIVE: To evaluate the effect of a continuous combined oral hormone replacement therapy (HRT) on basal and post-methionine load homocysteine levels in postmenopausal women. DESIGN: Twenty-two postmenopausal women (PMW) were randomly allocated to receive either continuous combined oral HRT (2 mg of estradiol plus 1 mg of norethisterone acetate; n = 11) or no treatment (controls, n = 11) for 6 months. A methionine oral load (0.1 g/kg body weight) was performed in each subject at time 0 and after 6 months. Serum homocysteine levels were measured by high-performance liquid chromatography in samples collected at time 0 and at 4, 8, and 24 h after the methionine load, while levels of vitamin B6 (by high-performance liquid chromatography) and B12 and folate (both by ELISA) were assayed in samples collected at time 0. RESULTS: Serum levels of glucose and body mass index increased in treated PMW, whereas folate decreased in controls. In treated PMW, basal homocysteine tended to decrease (10.6 +/- 3.3 micromol/L vs. 9.62 +/- 2.8 micromol/L, p = 0.062), whereas in controls it significantly increased (10.7 +/- 2.65 micromol/L vs. 12.17 +/- 3.89 micromol/L, p < 0.05). This increase was not significant after correction for vitamin status (p = 0.072). Homocysteine values 4 h (31.9 +/- 13.53 micromol/L vs. 39.83 +/- 22.53 micromol/L, p < 0.05) and 8 h (35.1 +/- 13.13 vs. 43.34 +/- 22.15 micromol/L) after methionine, and integrated homocysteine response to methionine (392.5 +/- 133.8 micromol/24 h vs. 458.8 +/- 104.8 micromol/24 h; p < 0.05), were significantly reduced in HRT-treated, but not in untreated, PMW. CONCLUSIONS: Continuous combined oral HRT with17beta-estradiol plus norethisterone acetate reduces homocysteine levels, mainly after a methionine load. This effect seems to be independent of vitamin status and may have positive implications for the prevention of cardiovascular diseases in PMW.

Transdermal administration of estradiol and norethisterone: effect on the uterus and uterine arteries.

OBJECTIVE: To evaluate the short- and long-term effect on the uterus, endometrium, and vascular reactivity of uterine arteries of sequential transdermal estradiol (50 microg/day) and norethisterone (0.25 mg/day in the last 14 days of each cycle). DESIGN: An intravaginal ultrasound evaluation was performed in 48 postmenopausal women before and at the 3rd and 12th month of treatment, during the last 3 days of both estradiol alone and estradiol plus norethisterone. An endometrial biopsy was also performed before and at the end of treatment. In 11 participants, intravaginal ultrasound and endometrial biopsy were repeated after 48 months of treatment. RESULTS: Uterine volume (33.7 +/- 3.3 cm3 to 56.8 +/- 3.7 cm3; p = 0.001) and endometrial thickness (3.07 +/- 0.48 mm to 5.74 +/- 0.41 mm; p = 0.001) increased within 3 months, with no further increases. Thickness was similar in the estradiol and estradiol-norethisterone phase. Endometrial hyperplasia was found in one participant at 12 months of treatment. A significant decrease (p = 0.002) in the pulsatility index of uterine arteries was observed only during the estradiol phase. After 48 months of treatment, the pulsatility index of uterine arteries was lower than at baseline (2.78 +/- 0.24 vs. 2.23 +/- 0.33; p = 0.044) even when evaluated in the combined phase. CONCLUSIONS: The transdermal administration of sequential estradiol and norethisterone reduces uterine artery resistance and induces a self-limiting growth of the uterus and endometrium.

Effect of desogestrel-containing oral contraceptives on vascular reactivity and catecholamine levels.

The modifications induced by new oral contraceptives (OC) on blood pressure, great vessel vascular reactivity by color Doppler, and catecholamine levels were investigated. Young healthy women not taking OC (n = 22; controls) or receiving, for > or = 6 months, OC containing desogestrel with either 30 micrograms (n = 14) or 20 micrograms of EE (n = 8) were enrolled. Blood pressure measured at rest in supine position was similar between controls and OC users. The pulsatility index (PI), an indirect index of resistance to blood flow, of axillary artery was significantly higher (p < 0.05) in 30 micrograms than in 20 micrograms EE OC users or controls. A similar trend, albeit not significant, was observed for the internal carotid artery PI. Norepinephrine (p < 0.01) and dopamine (p < 0.05) but not epinephrine levels, were lower in 30 micrograms EE OC users than in 20 micrograms EE OC users or controls. Thus, both 20 micrograms and 30 micrograms EE OC had no negative effect on blood pressure, but the 30 micrograms EE OC tended to increase great vessel resistance to blood flow, independently of catecholamine levels.

PIP: The effects on blood pressure of oral contraceptives (OCs) containing desogestrel plus either 20 or 30 mcg of ethinyl estradiol were investigated in 22 women who had been using one of these formulations for 6 months or more and 22 matched controls. There were no significant differences between both groups of cases and controls in blood pressure measured at rest in supine position. However, subtle differences were recorded in vascular reactivity, as evaluated by color Doppler ultrasound investigation. Compared to controls and users of OCs containing 20 mcg of ethinyl estradiol, cases taking OCs consisting of 30 mcg of ethinyl estradiol had a significantly higher pulsatility index in the axillary artery, indicating increased vessel resistance to blood flow. A similar, although not significant, trend was found in the internal carotid artery pulsatility index. On the other hand, catecholamine (dopamine and norepinephrine) levels were reduced by both OCs in a dose-dependent manner. Overall, these findings suggest that third-generation OCs, especially those containing 20 mcg of ethinyl estradiol, exert minimal effects on circulatory parameters. It is hypothesized that the cardiovascular effects of catecholamine reduction are antagonized by other mechanisms, among them the stimulus on the renin-angiotensin system.

Role of goserelin-depot in the clinical management of uterine fibroids.

On 30 women suffering from uterine fibroids, the monthly subcutaneous administration of goserelin depot (3.6 mg) for 6 (n = 22) or 12 months (n = 8) induced an about 50% shrinkage of uterus and fibroid volume, and within 3 months, an increase in the haematocrit value, with no metabolic side effects or detectable bone demineralization, evaluated by single photon absortiometry at distal radius. Both uterine and fibroid volumes reversed to pretreatment values after 3 months of goserelin depot withdrawal. In comparison with untreated subjects, on another 10 patients a three month administration of goserelin depot reduced the loss of blood during the surgical removal of the uterus or fibroids. Present data indicate that goserelin depot is effective and relatively safe in the medical management of uterine fibroids. Although, goserelin depot cannot yet be proposed as a definite medical therapy, it may represent a useful instrument in the presurgical management of uterine fibroids.

Use of contraception by women with induced abortion in Italy.

AIM: Aim of the present study was to investigate type of contraception, if any, used by women with induced abortion. METHODS: Retrospective analysis on the medical records of 1782 women with induced abortion performed at the University Hospital of Modena (Italy) between 2009 and 2011. RESULTS: Some kind of contraception was used by 81.1% of women with induced abortion. At time of conception most of these women (39%) had used withdrawal, 19% natural methods, 15.2% condom, 7% hormonal contraception (95% estrogen plus progestin for any route) and 0.4% copper-IUD. None was using implants or levonorgestrel-IUD. Figures of past use of hormonal contraception were much higher than those present at the time of the unwanted pregnancy (50.3% vs. 7%; P<0.0001). A higher prevalence of condom use (19.7% vs. 10.9%; P<0.0001), and a lower prevalence of natural methods (14.5% vs. 21.6%; P<0.001) were found in single vs. married women. Use of no contraception was more prevalent among low vs. highly educated women with induced abortion (22.2% vs. 14.2%; P<0.02), but was not related to marital status. Prevalence of use of the different contraceptives is different from the one described in the general population, suggesting differences in contraceptive efficacy among the different methods. CONCLUSION: Women with induced abortion infrequently use long term or hormonal contraception. In half of the cases the latter has been used at least once in life, but then it has been abandoned. Appropriate education and contraceptive counselling, personalization and follow-up may reduce induced abortion.

Early outcome of myomectomy by laparotomy, minilaparotomy and laparoscopically assisted minilaparotomy. A randomized prospective study.

BACKGROUND: To compare in the first 7 days after surgery the outcome of myomectomy performed by three laparotomic approaches: laparotomy (LT), minilaparotomy (MLT) and laparoscopically assisted minilaparotomy (LA-MLT). METHODS: Fifty-one women with 5-15 cm total myoma diameter were randomized blindly using a computer randomization list, to LT (n = 17), MLT (n = 17) or LA-MLT (n = 17). RESULTS: Mean operation length was similar in the three groups. Mean (+/- SEM) time of paralytic ileus (55.0 +/- 4.5 versus 33.4 +/- 3.4 h; P < 0.01) and discharge (141.6 +/- 5.2 versus 81.5 +/- 8.2 h; P < 0.01) was longer in LT than LA-MLT or even MLT. In comparison with LA-MLT, LT induced a greater haemoglobin decline (-3.07 +/- 0.3 versus -1.8 +/- 0.15 mg/dl; P < 0.025), and a greater post-operative stress, as documented by increased prolactin (+15.1 +/- 3.8 versus +0.16 +/- 4.5 ng/ml; P < 0.03) and decreased insulin sensitivity (fasting glucose/insulin; -7.5 +/- 2.6 versus -0.7 +/- 2.1; P < 0.02). Seven days after surgery, abdominal pain (P < 0.05) was higher after LT (3.0 +/- 0.6) than MLT (0.5 +/- 0.2) and LA-MLT (0.9 +/- 0.4). CONCLUSIONS: In selected cases, myomectomy by LA-MLT offers some advantages versus LT and, to a smaller extent, MLT.

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.

Potentially beneficial cardiovascular effects of melatonin administration in women.

The cardiovascular effects induced by the daytime administration of melatonin (1 mg) were compared to those of placebo in 12 young women. In order to eliminate cardiovascular effects due to fluctuating endogenous sex steroids, all women were taking a fixed dose of monophasic contraceptive pill. In comparison to placebo, the administration of melatonin reduced, within 90 min, the pulsatility index of the internal carotid artery, evaluated by color Doppler ultrasound (P < 0.01), as well as both systolic and diastolic blood pressure evaluated in supine position (P < 0.01). Supine catecholamine levels were not significantly modified, but norepinephrine levels evaluated after 5 min of standing position were significantly reduced (P < 0.02). These data suggest that in women the administration of 1 mg of melatonin may exert beneficial effects on blood vessels.

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.

Effect of ovarian suppression on glucose metabolism of young lean women with and without ovarian hyperandrogenism.

Gonadal steroids are believed to influence glucose metabolism, oestrogens inducing an improvement and androgens or progestins a deterioration. At baseline and after 3 months of ovarian suppression with a gonadotrophin-releasing hormone analogue (GnRHa: goserelin depot 3.75 mg/28 days), glucose metabolism was evaluated in eight lean women affected by ovarian hyperandrogenism (PCOS) and six age-weight-matched non-hyperandrogenic women (controls) by using both an oral glucose tolerance test (75 g; OGTT) and the minimal model method. The latter method allows calculation of peripheral insulin sensitivity (Si) and glucose dependent glucose utilization (Sg). In PCOS, higher fasting concentrations (P < 0.05) of insulin and C-peptide, and lower Sg (P < 0.05) and Si (P < 0.01) were found. GnRHa did not significantly modify glucose metabolism of controls, while in women with PCOS it decreased fasting glucose (P < 0.05) and significantly increased Si (P < 0.03) up to control values. The present data indicate that strong suppression of ovarian activity improves Si in lean women with PCOS, while it is without relevant effects on glucose metabolism of non-hyperandrogenic women.

Oral contraceptives and vascular reactivity of great vessels in women.

Blood pressure and great vessel vascular reactivity, evaluated by color Doppler ultrasound, were investigated in users of third-generation oral contraceptives (n = 18) compared to non-users, who were studied either in the follicular (n = 8) or in the luteal (n = 10) phase of the menstrual cycle. Blood pressure measured at rest in the supine position, evaluated both in the follicular phase and in the luteal phase, was similar between oral contraceptive users and non-users. The pulsatility index (an indirect index of resistance to blood flow) of both the internal carotid artery and the axillary artery was similar in control women studied in the follicular phase and in the luteal phase. By contrast, in users of oral contraceptives, pulsatility index values of the internal carotid artery tended to be higher, whilst those of the axillary artery were significantly higher, than those of women in either the follicular phase (p < 0.01) or the luteal phase (p < 0.025). In conclusion, new third-generation oral contraceptives do not have a significant impact on blood pressure control, but still tend to increase vascular resistance to blood flow, particularly in areas more involved in the regulation of blood pressure, for example the axillary artery.

Influences of melatonin administration on the circulation of women.

The cardiovascular effects induced by the daytime administration of melatonin (1 mg) were compared with those of placebo in 17 young, healthy, early follicular-phase women. Compared with placebo, the administration of melatonin modified, within 90 min, the pulsatility index (PI), evaluated by color Doppler ultrasound, of the internal carotid artery, abdominal aorta, and axillary artery. The effect was linearly related to baseline PI, higher baseline PI being associated with greater PI declines. Melatonin administration significantly decreased mean PI of internal carotid artery (P < 0.02), systolic and diastolic blood pressure (P < 0.01), and norepinephrine levels evaluated after 5 min of standing position (P < 0.02). Heart rate and supine catecholamine levels were not modified. These data indicate that in young, healthy women the administration of 1 mg of melatonin greatly influences artery blood flow, decreases blood pressure, and blunts noradrenergic activation. Clinical implications of present data are worthy to be fully explored.

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.

Different circulatory response to melatonin in postmenopausal women without and with hormone replacement therapy.

In young men and women, melatonin influences vascular reactivity and reduces blood pressure and norepinephrine levels. Herein, we investigated whether these effects are conserved in postmenopausal women without and with hormone replacement therapy (HRT). Oral melatonin (1 mg) or placebo was randomly and in double blind fashion administered to 18 untreated and 13 postmenopausal women who were treated continuously with transdermal estradiol (50 microg/day) plus cyclic medroxyprogesterone acetate (5 mg/day x 12 days every 28 days). Internal carotid artery pulsatility index (PI), an index of downstream resistance to blood flow, blood pressure and catecholamine levels were evaluated. In untreated postmenopausal women, melatonin was ineffective, while in HRT-treated women, studied during the only estrogenic phase, melatonin reduced, within 90 min, systolic (-8.1 +/- 9.9 mmHg; P = 0.054), diastolic (-5.0 +/- 7.0 mmHg; P = 0.049) and mean (- 6.0 +/- 6.6 mmHg; P = 0.037) blood pressure. Norepinephrine (-50.1 +/- 66.7 pg/mL; P = 0.019), but not epinephrine levels, were also significantly reduced. Similarly, resistance to blood flow in the internal carotid artery, as evaluated by the PI, decreased (-0.190 +/- 0.15; P = 0.0006) in a way that was linearly related to pre-existing PI values (r2 = 0.5; P = 0.0059). These data show that the circulatory response to melatonin is conserved in postmenopausal women on HRT but not in untreated postmenopausal women. Possible physiological and pharmacological implications of these data on the cardiovascular risk of postmenopausal women can be envisioned.

Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women.

OBJECTIVE: The effect of melatonin on human carbohydrate metabolism is not yet clear. We investigated whether melatonin influences glucose tolerance and insulin sensitivity in aged women. PATIENTS: Twenty-two postmenopausal women of whom 14 were on hormone replacement therapy. DESIGN: After an overnight fast, at 0800 hours on two nonconsecutive days, placebo or melatonin (1 mg) were administered randomly and in a double blind fashion. Forty-five minutes later, an oral glucose tolerance test (75 g; OGTT) was performed in 13 women. In another nine women insulin-dependent (Si) and -independent (Sg) glucose utilization was tested by a frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS: Areas under the response curve to OGTT (AUC) for glucose (1420 +/- 59 vs. 1250 +/- 55 mmol x min/l; P < 0.01), and C-peptide (42,0980 +/- 45,320 vs. 33,528 +/- 15,779 pmol x min/l; P < 0.02) were higher following melatonin than placebo, while Si values were lower (2.6 +/- 0.28 units vs. 3.49 +/- 0.4 units; P < 0.03). Si modifications induced by melatonin were inversely related to Si values of the placebo day (r(2) = 0.538; P < 0.025). CONCLUSIONS: The present results indicate that in aged women administration of 1 mg of melatonin reduces glucose tolerance and insulin sensitivity. The present data may have both physiological and clinical implications.