Drospirenone and cardiovascular risk in lean and obese polycystic ovary syndrome patients: a pilot study.

OBJECTIVE: We sought to verify if an oral contraceptive (OC) containing drospirenone affects the cardiovascular risk of patients with polycystic ovary syndrome (PCOS). STUDY DESIGN: A total of 28 women with PCOS (16 lean [group A] and 12 overweight [group B]) were assessed at baseline and after 6 months therapy with an OC. Leptin, homocysteine, endothelin-1, and flow-mediated dilatation of brachial artery were measured. RESULTS: The brachial artery diameter and the pulsatility index, after the reactive hyperemia, did not change in group A; it improved significantly in group B after 6 months of treatment. At baseline and after therapy the plasma levels of homocysteine and endothelin-1 did not differ among the groups. Leptin was significantly lower at baseline in group A compared to group B. CONCLUSION: The OC containing drospirenone does not seem to affect the surrogate markers of cardiovascular risk in lean patients with PCOS.

Periovulatory morphometric and vascular modifications of the clitoris in young adult and middle-aged women. A pilot study.

INTRODUCTION: A decline in sexual activity has been reported as women age. AIM: To compare, in young adult and middle-aged women, the clitoral volumetric and vascular modifications during the periovulatory phase of the menstrual cycle, and to analyze their relationship with circulating hormones, nitric oxide levels, and with questionnaires on sexuality, relationship, and depression. METHODS: Fifteen young (18-25 years; Group I), and 16 middle-aged (35-45 years; Group II) eumenorrheic women were submitted, on day 14 of their menstrual cycle, to utero-ovarian and clitoral ultrasonographic analysis, and to color Doppler evaluation of the uterine and dorsal clitoral arteries. On the same day, hormonal parameters and plasma concentrations of nitrites/nitrates were assayed, and the two-factor Italian McCoy female questionnaire and the Beck's Depression Inventory questionnaire were administered. MAIN OUTCOMES MEASURES: Utero-ovarian and clitoral ultrasonographic analysis, color Doppler evaluation of the uterine and dorsal clitoral arteries; evaluation of hormonal and nitrites/nitrates plasma concentrations; administration of the two-factor Italian McCoy Female Sexuality Questionnaire and the Beck's Depression Inventory questionnaire. RESULTS. The plasma levels of estradiol, testosterone, sex hormone binding globulin, and nitrites/nitrates were similar in both groups. Neither the ultrasonographic assessment of the clitoral body volume (0.82 +/- 0.24 mL vs. 0.73 +/- 0.26 mL) nor the Doppler analysis of the dorsal clitoral artery [pulsatility index (PI) = 1.35 +/- 0.31 vs. PI = 1.36 +/- 0.19] evidenced any significant differences in either Group I or Group II. The two-factor Italian McCoy Female Sexuality Questionnaire and the Beck Depression Inventory questionnaire gave the same results in Group I and Group II. The relationship between the different parameters evidenced that the NO(2-)/NO(3-) circulating levels are inversely correlated with uterine artery (r = -0.4611; P = 0.008) and dorsal clitoral artery (r = -0.331; P = 0.041) PIs. Furthermore, estradiol resulted inversely correlated with depression (r = -0.332; P = 0.045). The two sections (sexuality and partnership) of Italian McCoy Female Sexuality Questionnaire were positively correlated (r = 0.849; P < 0.0001) between each other. CONCLUSIONS: In eumenorrheic young adult and middle-aged women, the periovulatory clitoral anatomic and vascular modifications similarly occur.

Genistein supplements might not induce clitoral modifications in postmenopausal women: a prospective, pilot study.

INTRODUCTION: Vaginal dryness, low sexual desire, and low sexual arousability are critical issues for many postmenopausal women. Hormone therapy seems to improve vaginal lubrication and dyspareunia. AIM: To evaluate, in postmenopausal women who refused hormonal therapy, the role of genistein in the treatment of vasomotor symptoms and its capacity to induce clitoral volumetric and vascular modifications independently from sexual stimulation. METHODS: Twenty-nine postmenopausal women who refused hormonal therapy were submitted to oral daily treatment with genistein 45 mg (Group I; N = 15); or no treatment (Group II; N = 14). The Group II patients served as controls. The patients were not randomly assigned to the two groups. The patients were studied before and after 3 months. MAIN OUTCOMES MEASURES: Endometrial and clitoral ultrasonographic analysis; color Doppler evaluation of the dorsal clitoral artery; evaluation of hormonal plasma concentrations; administration of the two-factor Italian McCoy Female Sexuality Questionnaire; compilation of a monthly diary reporting the number of hot flashes. The ultrasound, color Doppler and psychometric tests were performed by examiners blinded to the participant's group assignment. RESULTS: In the genistein-treated patients the vasomotor symptoms ameliorated at the end of the study. The use of genistein did not influence any other parameter. CONCLUSIONS: Postmenopausal women submitted to a 3-months treatment with genistein showed an improvement of vasomotor symptoms. However, isoflavones seem to not induce any modification in the clitoral structures.

Angeliq versus Activelle in normotensive postmenopausal women: a prospective, randomized pilot study.

OBJECTIVE: The aim of this study was to compare, in normotensive postmenopausal women, the effects of drospirenone/estradiol and norethisterone acetate/estradiol on blood pressure and other surrogate markers of cerebrovascular and cardiovascular risk. METHODS: Thirty postmenopausal women were submitted to utero-ovarian ultrasonography and to color Doppler evaluation of ophthalmic arteries. Ultrasonographic and Doppler analysis of brachial artery flow-mediated vasodilatation and 24-hour ambulatory blood pressure monitoring were performed. Plasma concentrations of nitrites/nitrates were assayed. The participants were randomly assigned to drospirenone 2 mg/estradiol 1 mg (group 1; n = 15) or norethisterone acetate 0.5 mg/estradiol 1 mg (group 2; n = 15) treatment. The duration of the study was 6 months. RESULTS: The basal pulsatility index and the back pressure of the ophthalmic artery were similar in groups 1 and 2. After 6 months, no changes were observed. The nitrites/nitrates values were not different between groups 1 and 2 both in basal conditions and after therapy. The brachial artery flow-mediated vasodilatation and the pulsatility index of the brachial artery did not show any difference in groups 1 and 2 both in basal conditions and after the therapy. The 24-hour blood pressure monitoring showed no significant differences in the 24-hour time, daytime, and nighttime values either in basal conditions or after therapy. All participants were found to be dippers normally (nocturnal reduction > or =10% in comparison with diurnal values). The wake-up blood pressure values were similar in the studied participants. CONCLUSIONS: A 6-month hormone therapy with drospirenone/estradiol or norethisterone acetate/estradiol is equally effective and does not seem to alter the surrogate markers of cardiovascular and cerebrovascular risk.

Ultrasonographic and Doppler findings of subclinical clitoral microtraumatisms in mountain bikers and horseback riders.

INTRODUCTION: Repeated microtraumas in horseback riders and mountain bikers are, in males, associated with perineal and scrotal lesions. No data are reported in the females. AIM: To report five cases of clitoral microcalcifications, diagnosed by ultrasonography, in six healthy, eumenorrheic athletes, and to verify the clinical and sexual impact of the ultrasonographic findings. MAIN OUTCOME MEASURES: Translabial ultrasonographic evaluation of the clitoris, Doppler analysis of dorsal clitoral arteries, and the two-factor Italian McCoy Female Sexuality Questionnaire (MFSQ) METHODS: The patients were assessed with a detailed history, and were submitted, in the periovulatory phase of the cycle (day 14), to clitoral ultrasonographic analysis and color Doppler evaluation of the dorsal clitoral arteries. The women were not sexually aroused. On the same day, in a separate room--and prior the ultrasound and Doppler examinations took place--the subjects completed the two-factor Italian MFSQ. RESULTS: All the patients were completely asymptomatic but reported a past history of intermittent perineal tenderness or discomfort. In five out of the six subjects, the ultrasonographic assessment of the clitoris evidenced a disseminated clitoral microlithiasis. Only the youngest (18 years old) biker showed a normal pattern of the clitoral structures. A normal clitoral body volume (0.68 +/- 0.21 mL) and a normal mean dorsal artery pulsatility index (PI) was found (PI = 1.75 +/- 0.32) in all the patients. The two-factor Italian MFSQ showed a mean value of 42 +/- 4 (range 37-45). CONCLUSIONS: The chronic traumatisms may be responsible, especially in well-trained riders, for microhematomas, inflammation, and/or degenerative processes at level of the clitoral structure. Further studies should be undertaken to determine the clinical significance of the described disseminated clitoral microlithiasis.

Cardiovascular risk in normal weight, eumenorrheic, nonhirsute daughters of patients with polycystic ovary syndrome: a pilot study.

OBJECTIVE: To verify whether healthy daughters with polycystic ovaries (PCO) of patients with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease in comparison with healthy controls. DESIGN: Prospective observational study. SETTING: University hospital. PATIENT(S): Seventeen eumenorrheic daughters with PCO of patients with PCOS (group 1) and 20 healthy volunteers (group 2) with regular ovulatory cycles. INTERVENTION(S): Fasting blood sampling, ultrasonographic and Doppler analyses, 24-hour ambulatory blood pressure monitoring. MAIN OUTCOME MEASURE(S): Medical examination; blood measurement of nitrites and nitrates, biochemical and hormonal parameters; utero-ovarian ultrasonographic analysis and color Doppler evaluation of uterine and stromal ovarian arteries; brachial artery flow-mediated vasodilatation; 24-hour ambulatory blood pressure monitoring. An oral glucose tolerance test was performed to analyze glucose, insulin, and C-peptide levels. RESULT(S): At Doppler analysis a significantly higher uterine and a lower ovarian artery pulsatility index was found in group 1 compared with group 2. The brachial artery diameter, after the reactive hyperemia, showed a greater vasodilatation in controls in comparison with women with PCO. The 24-hour blood pressure monitoring demonstrated that patients with PCO have significant higher 24-hour, daytime, and nighttime diastolic and mean arterial pressure values than controls. The nitrites and nitrates plasma levels were lower in group 1 compared with group 2. The glucose and insulin plasma values were higher in patients with PCO than in controls. CONCLUSION(S): Eumenorrheic nonhirsute daughters of patients with PCOS who have PCO appearance on ultrasound have an increased cardiovascular risk.

Endothelial function and its relationship to leptin, homocysteine, and insulin resistance in lean and overweight eumenorrheic women and PCOS patients: a pilot study.

OBJECTIVE: To verify if patients with polycystic ovarian syndrome (PCOS), have an increased cardiovascular risk compared with healthy controls. DESIGN: Prospective case-control study. SETTING: University-based practice. PATIENT(S): Twenty eumenorrheic controls (ten lean [group A] and ten overweight [group B]) and 24 PCOS women (14 lean [group C] and ten overweight [group D]). INTERVENTION(S): Cardiovascular risk markers and hormonal parameters were assessed. MAIN OUTCOME MEASURE(S): Androgens, fasting glucose, insulin, leptin, fibrinogen, homocysteine, endothelin-1 and flow-mediated dilatation of the brachial artery were measured to investigate their relationship to weight and to PCOS. RESULT(S): The brachial artery diameter and the pulsatility index, after the reactive hyperemia, showed in group A the most intense vasodilatation compared with the other groups. Homocysteine levels did not differ among the groups. Endothelin-1 was significantly higher in group A compared with groups B and D. Leptin was significantly lower in groups A and C compared with groups B and D. Insulin resistance was higher in groups B and D. Group A had significantly higher glucose-insulin ratio compared with all of the other groups; group C had significantly higher glucose-insulin ratio only compared with group D. CONCLUSION(S): Weight and PCOS are two independent variables affecting the endothelial function.

PCOS, sexuality, and clitoral vascularisation: a pilot study.

INTRODUCTION: In polycystic ovarian syndrome (PCOS) women, the changes in body appearance (mainly obesity and hirsutism) may influence the feminine identity of the patients with consequent depression and sexual disturbances. AIM: To evaluate if lean PCOS patients present an increased incidence of depression and sexual dysfunction in comparison with controls and if clitoral volume and vascularization are influenced by circulating androgens levels. METHODS: 25 lean PCOS women (Group I) and 18 healthy nonhirsute volunteers (Group II) were submitted, on day 3-5 of the cycle, to ultrasonographic and Doppler analyses, and to hormonal and biochemical evaluations. MAIN OUTCOME MEASURES: Utero-ovarian and clitoral ultrasonographic analysis, and color Doppler evaluation of the uterine, stromal ovarian, and dorsal clitoral arteries. Hormonal and nitrites/nitrates plasma concentrations were analyzed. Each woman filled in the 2-factor Italian McCoy female questionnaire (MFSQ) and the Beck's Depression Inventory questionnaire (BDI). RESULTS: Androgens resulted, as expected, more elevated in PCOS patients than in controls. However, the ultrasonographic (US) assessment of the clitoral body volume evidenced no significant differences between PCOS (0.72+/-0.41 mL) and control (0.62+/-0.20 mL) patients. The resistances registered at the level of the dorsal clitoral artery did not show any difference between Group I (PI=1.55+/-0.40) and Group II (PI=1.79+/-0.38). The 2-factor Italian MFSQ and the BDI did not show any difference between PCOS women and controls. CONCLUSIONS: In PCOS women, probably, the moderate hirsutism and hyperandrogenism do not induce the sense of loss of feminine identity and have no impact on sexual self-worth and sexual satisfaction.

Menstrual cycle-related morphometric and vascular modifications of the clitoris.

INTRODUCTION: The evaluation of clitoral anatomy and function is of paramount importance to understand the physiology and pathology of clitoral function. AIM: To prospectively evaluate the clitoral volumetric and vascular modifications during the menstrual cycle, and analyze their relationship with circulating hormones and nitric oxide levels. METHODS: Thirty healthy eumenorrheic women were studied in different phases of the menstrual cycle (day 3, 10, 14, 20, and 27). They were submitted to ultrasonographic (US) and Doppler analyses, and to hormonal and biochemical evaluations. MAIN OUTCOME MEASURES: Transvaginal US evaluation of uterus, ovaries, and clitoris; Doppler analysis of uterine and dorsal clitoral arteries; and measurement of plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, androstenedione, testosterone, and nitrites/nitrates concentration. Sex hormone binding globulin was assayed, and free androgen index was calculated. RESULTS: During the menstrual cycle, FSH, LH, and estradiol changed as expected, whereas androgens did not show any significant change. The US assessment of the clitoral body volume evidenced a progressive increase with significant modifications during the periovulatory phase, after which it remained stable until day 20. Subsequently, the clitoral body volume decreased into the premenstrual phase (day 27), reaching values similar to those observed on cycle day 3. A comparable trend was observed in the nitrite/nitrate circulating values. The uterine and clitoral arteries presented significant modifications with reduced resistances in the periovulatory period. Estradiol levels resulted positively correlated with the clitoral body volume and inversely correlated with the dorsal clitoral artery pulsatility index (PI). Furthermore, the dorsal clitoral artery PI was inversely and significantly correlated with the nitrite/nitrate circulating values and the clitoral body volume. CONCLUSIONS: Clitoral anatomic and vascular modifications are observable during the normal menstrual cycle.

Vascular risk in young women with polycystic ovary and polycystic ovary syndrome.

OBJECTIVE: To estimate if young polycystic ovary syndrome (PCOS) patients have subclinical risks of vascular disease compared with eumenorrheic polycystic ovary (PCO) women and healthy controls. METHODS: Twenty-eight PCOS patients, 17 eumenorrheic PCO women, and 15 healthy eumenorrheic volunteers underwent medical examination; blood measurement of nitrites/nitrates, biochemical and hormonal parameters; uteroovarian ultrasonographic analysis and color Doppler evaluation of uterine, stromal ovarian, and ophthalmic arteries; brachial artery flow-mediated vasodilatation; 24-hour ambulatory blood pressure monitoring. An oral glucose tolerance test was performed to analyze glucose, insulin, and C-peptide. RESULTS: Doppler analysis revealed a significantly higher uterine pulsatility index in the PCOS group compared with controls. The lowest vascular resistances in the ovaries were found in PCOS and PCO compared with controls. The ophthalmic artery back pressure was significantly higher in women with PCOS than in controls. The brachial artery diameter, at baseline, was similar in all the participants. After the reactive hyperemia, a greater vasodilatation was observed in controls and PCO patients in comparison with PCOS women. Total cholesterol, triglycerides, and the atherogenic plasma index were significantly higher in PCOS than PCO and controls. Leukocytes and homocysteine were slightly higher in PCOS. The nitrites/nitrates plasma levels were lower in PCOS and PCO patients compared with controls. The insulin and C-peptide plasma values were higher in PCOS patients than controls. In PCOS patients the different estimates of insulin sensitivity and pancreatic beta-cell function were higher compared with PCO and controls. CONCLUSION: Polycystic ovary syndrome is a condition associated with an increased vascular risk. LEVEL OF EVIDENCE: II.