Fulvia Mancini

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 β-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

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.

Polycystic ovary syndrome and cardiovascular risk in young patients treated with drospirenone-ethinylestradiol or contraceptive vaginal ring. A prospective, randomized, pilot study

OBJECTIVE To compare the effects of a pill containing drospirenone with those of a combined contraceptive vaginal ring on the lipid and carbohydrate metabolism and on the surrogate markers of arterial function. SETTING Bologna University School of Medicine. PATIENT(S) Thirty-seven women with polycystic ovary syndrome (PCOS) were randomly submitted to drospirenone+ethinylestradiol (group I; n=19) or combined contraceptive vaginal ring (group II; n=18) therapy. The duration of the study was 6 months. INTERVENTION(S) The effect of treatments was assessed after 6 months of therapy. MAIN OUTCOME MEASURE(S) Utero-ovarian ultrasound analysis and color Doppler evaluation of uterine and stromal ovarian arteries. In addition, analysis of brachial artery flow-mediated vasodilatation and 24-hour ambulatory blood pressure monitoring were performed. Fasting blood samples were drawn for testing biochemical and hormonal parameters and nitrites/nitrates. RESULT(S) Both treatments improved hirsutism, hyperandrogenemia, and ultrasound and color Doppler ovarian parameters. Both drospirenone+ethinylestradiol or contraceptive vaginal ring induced a slight but significant increase of diurnal and 24-hour blood pressure. Although both therapies worsened the lipid profile, the oral pill administration was associated with a more evident increase of circulating triglycerides. The 6-month treatment with the vaginal ring significantly improved the area under the curve for glucose, insulin, and C-peptide, whereas the drospirenone+ethinylestradiol pill induced an increase in the insulinogenic index and homeostatic model assessment estimate for insulin resistance values. CONCLUSION(S) Vaginal hormonal contraception appears to be preferable to oral ethinylestradiol + drospirenone administration in hyperinsulinemic patients with PCOS.

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 Becks 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.

Neuroendocrine recovery initiated by cognitive behavioral therapy in women with functional hypothalamic amenorrhea: a randomized controlled trial

OBJECTIVE To determine whether cognitive behavior therapy (CBT), which we had shown in a previous study to restore ovarian function in women with functional hypothalamic amenorrhea (FHA), could also ameliorate hypercortisolemia and improve other neuroendocrine and metabolic concomitants of in FHA. DESIGN Randomized controlled trial. SETTING Clinical research center at an academic medical university. PATIENT(S) Seventeen women with FHA were randomized either to CBT or observation. INTERVENTION(S) CBT versus observation. MAIN OUTCOME MEASURE(S) Circulatory concentrations of cortisol, leptin, thyroid-stimulating hormone (TSH), total and free thyronine (T(3)), and total and free thyroxine (T(4)) before and immediately after completion of CBT or observation. (Each woman served as her own control.) RESULT(S) Cognitive behavior therapy but not observation reduced cortisol levels in women with FHA. There were no changes in cortisol, leptin, TSH, T(3), or T(4) levels in women randomized to observation. Women treated with CBT showed increased levels of leptin and TSH, but their levels of T(3) and T(4) remained unchanged. CONCLUSION(S) In women with FHA, CBT ameliorated hypercortisolism and improved the neuroendocrine and metabolic concomitants of FHA while observation did not. We conclude that a cognitive, nonpharmacologic approach aimed at alleviating problematic attitudes not only can restore ovarian activity but also improve neuroendocrine and metabolic function in women with FHA. CLINICAL TRIAL REGISTRATION NUMBER NCT01674426.

Sexual Behavior and Oral Contraception: A Pilot Study

INTRODUCTION Oral contraceptives (OCs) induce mood and libido changes. AIM The aim of this study was to evaluate in young, eumenorrheic, healthy women the sexual behavior and the genital vascular effects of an OC containing 30 µg ethinylestradiol (EE) and 3 mg drospirenone (DRSP). MAIN OUTCOME MEASURES The main outcome measures are McCoy Female Sexuality Questionnaire (MFSQ), the labia minora thickness and vaginal introitus area, the pulsatility index (PI) of clitoral and labia minora arteries, and hormonal and biochemical assays. METHODS Twenty-two adult, eumenorrheic, healthy women were administered the two-factor Italian MFSQ. The labia minora thickness was studied by two-dimensional ultrasonographic, and the clitoral and labia minora arteries were evaluated by color Doppler; three-dimensional static volumes of the vulvar area were calculated. Hormonal (estradiol, androstenedione, and testosterone) and biohumoral (sex hormone binding globulin) parameters were assayed. Subjects were studied in baseline conditions and after 3 months of therapy with an OC (Yasmin®, Bayer-Schering Italia, Milan, Italy; -30 µg EE + 3 mg DRSP). RESULTS After 3-month treatment, the labia minora thickness and the vaginal introitus area significantly decreased in comparison with the baseline values, whereas the PI of the dorsal clitoral artery and the posterior labial artery significantly increased. The OC use induced a significant decrease of the two-factor Italian MFSQ score, a reduction of the number of intercourse/week, and a reduction of the frequency of orgasm during intercourse. The item 18 (pain during intercourse) worsened after OC. CONCLUSIONS The treatment with Yasmin® (Bayer-Schering Italia) is associated with increased pain during intercourse, with decreased libido and spontaneous arousability, and with diminished frequency of sexual intercourse and orgasm.

Pelvic ultrasound and color Doppler findings in different isosexual precocities

To evaluate the role of ultrasound and color Doppler analyses in improving the differential diagnosis of pubertal precocities.

Hormone therapy and ophthalmic artery blood flow changes in women with primary open-angle glaucoma

Objective To compare the effects of hormone therapy (HT) on plasma viscosity and Doppler flow parameters in normal, healthy, postmenopausal women and in women with normal-tension and chronic, open-angle glaucoma. Design Eight postmenopausal women with glaucoma (group I) and 15 controls (group II) were given HT. The duration of the study was 6 months, and the women were examined in basal condition and at the end of the treatment. All women underwent ultrasonographic evaluation of pelvic organs and color Doppler analysis of uterine, internal carotid, and ophthalmic arteries. Also, plasma viscosity was assayed. Results The ultrasonographic analysis showed that none of the women presented with irregular endometrial echoes, polyps, or intracavitary fluid. In addition, endometrial thickness never exceeded the normal range (5 mm). Plasma viscosity and Doppler parameters significantly improved during therapy. However, the ophthalmic artery mean improvements of pulsatility index (−43% v −28%; P = 0.001), peak systolic blood flow velocity (+35% v +24%; P = 0.026), and time-averaged maximum velocity (+44% v +32%; P = 0.031) were significantly more evident in the control group than in the glaucoma group. Conclusions Although, in people with glaucoma, vasospasm can increase the risk of visual loss by inducing a retrobulbar blood flow reduction, HT seems to beneficially affect the ocular vascularization.

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.

Low-dose flutamide (125 mg/day) as maintenance therapy in the treatment of hirsutism.

Objective: To evaluate the safety and efficacy of a low dose of flutamide (125 mg/day) in maintaining the clinical results already obtained using a higher dose (250 mg/day), in women suffering from hirsutism. Method: Forty-three women suffering from hirsutism of varying origin received 250 mg/day of flutamide as an initial treatment for 12 months and, subsequently, 125 mg/day of flutamide for an additional 12 months as a maintenance treatment. Hirsutism was evaluated by the Ferriman-Gallwey score, and hair diameter and hair growth rate were determined by a special image analysis processor. Biochemical, clinical and hormonal parameters were evaluated in basal conditions and every 2–6 months. Results: The significant decrease in the hirsutism score, hair diameter and hair growth rate during the initial treatment period was confirmed at the end of the maintenance treatment period. Androgen levels decreased up to the end of the initial treatment period and partially decreased during the maintenance treatment. During the initial treatment period, 4 subjects showed an increase of aspartate aminotransferase and alanine aminotransferase and dropped out. During the maintenance treatment period, no side effects or complications were observed. Conclusion: Satisfactory management of hirsutism with flutamide seems to be represented by an initial treatment period using 250 mg/day to achieve satisfactory results, followed by a long maintenance treatment period using 125 mg/day.