Antagonist rescue of agonist IVF cycle at risk of OHSS: a case series.

We describe a series of in vitro fertilisation (IVF) long protocol cycles presenting a risk of ovarian hyperstimulation syndrome (OHSS) which were rescued with an antagonist at a university-based tertiary-care fertility centre. Nineteen IVF patients presenting a risk of OHSS during treatment with long protocol, between 2009 and November 2012 were included in the present study. After discussion of available options, the agonist was stopped and a daily gonadotropin-releasing hormone (GnRH) antagonist injection was initiated ("rescue protocol") and maintained until ovulation trigger. Fourteen patients were triggered with human chorionic gonadotropin (hCG) and five with GnRH agonist bolus, yielding competent oocytes. Seventeen embryo transfers were performed in the fresh cycles. One patient developed moderate OHSS. There were eight clinical pregnancies after the fresh IVF cycle (42% per patient), and six further pregnancies after frozen-thawed cycles, resulting in a 73% cumulative clinical pregnancy rate within one year. We conclude that the "rescue protocol with antagonist" of the long IVF cycle with a high risk of OHSS allows us to carry on with the cycle, without compromising its success or the patient safety, thus broadening the possibility of applying the long protocol.

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.

Elective single embryo transfer and cumulative pregnancy rate: five-year experience in a Southern European Country.

To compare cumulative pregnancy and live birth rates of single embryo transfer (SET) vs. double embryo transfer (DET) in women <35 years old with good-quality embryos, we designed an observational prospective study carried out between October 2002 and December 2006. Patients who accepted SET were compared with those who decided DET. A total of 628 couples who underwent embryo transfers met the criteria for SET: 52% accepted it, while 47.8% asked for DET. Implantation rate was higher in SET, 46.6% (p < 0.05), whereas pregnancy rate (PR) per transfer was higher in DET, 38.3% (p < 0.05). Twin PR in DET was 26.4% compared with 0.7% in SET (p < 0.05). SET group performed 278 frozen embryo transfer and DET 128. The mean of embryos transferred was the same, resulting in similar pregnancy and twin PR (SET: 24.8% and 21.7% vs. DET: 25.0% and 28.1%). Cumulative PR was 66.2% in SET and 69.7% in DET, not showing significant differences (NS). Likewise, cumulative live birth rates did not show differences. Cumulative twin PR in SET was 7.2% and in DET 26.6%, (p < 0.05). Cumulative PR over time leveled at 15-18 months follow-up in both groups. In Conclusion, in order to reduce twins we support the promotion of SET.

Moderate alcohol intake, genital vascularization, and sexuality in young, healthy, eumenorrheic women. A pilot study.

INTRODUCTION: The relationship between alcohol and sexual function is complex and not completely understood. AIM: To evaluate (in the early follicular phase and independently from sexual stimulation) in young, eumenorrheic, healthy, lean women the genital vascular effects of the light and moderate use of alcohol. METHODS: Eighty-four women undertook, in the early follicular phase of the menstrual cycle (days 3-5), the administration of the two-factor Italian McCoy Female Sexuality (MFSQ) and the Beck Depression Inventory (BDI) questionnaires; ultrasonographic measurement of the carotid intima-media thickness (IMT); and color Doppler evaluation of the carotid, clitoral, and labia minora arteries. Hormonal (estradiol, androstenedione, and testosterone) and biochemical (lipids, glucose, and insulin) parameters were tested. MAIN OUTCOME MEASURES: The MFSQ and BDI questionnaires; the carotid IMT; the Pulsatility Index of internal carotid, clitoral, and labia minora arteries; blood pressure measurement; and hormonal and biochemical assays. RESULTS: The subjects were divided in: nondrinkers (group I); current (>1 year) light drinkers--1-10 drinks/month (group II); and current moderate drinkers--11-20 drinks/month (group III). The majority of the studied parameters did not vary among the different groups. The mean BDI was normal in the studied women. However, the lowest values were observed in the moderate drinkers group. The MFSQ did not show any difference among all the studied women. However, the number of intercourses/week and the incidence of vaginal orgasm were significantly higher in group III (moderate drinkers). The relationship between the drinking habits and different parameters showed an inverse relationship with the BDI. Furthermore, the BDI inversely correlated with orgasm frequency and with orgasm intensity. CONCLUSIONS: Chronic slight/moderate alcohol consumption has no effects on genital vessels and vaginal lubrication. However, a moderate consumption of alcohol, through psychological and social disinhibiting effects, may favor sexual activities.

Cigarette smoking decreases the genital vascularization in young healthy, eumenorrheic women.

INTRODUCTION: Cigarette smoking is a major health hazard and may impair the normal sexual response. AIM: To evaluate (in the early follicular phase, and independently from sexual stimulation) in young, eumenorrheic, healthy, lean women the general and genital vascular effects of the smoking habit. METHODS: One hundred thirty-seven patients undertook, in the early follicular phase of the menstrual cycle (day 3-5): the administration of the two-factor Italian McCoy Female Sexuality Questionnaire (MFSQ); two-dimensional (2-D) color Doppler evaluation of the ophthalmic, carotid, uterine, clitoral, and labia minora arteries; three-dimensional (3-D) analysis of clitoral and labia minora vascularization; and blood pressure evaluation. Fasting blood samples were drawn to test plasma estradiol, androstenedione, and testosterone circulating levels. MAIN OUTCOME MEASURES: The two-factor Italian MFSQ; the pulsatility index (PI) of internal carotid, ophthalmic, uterine, clitoral, and labia minora arteries; the vascularization index (VI), the flow index (FI), and the vascularization flow index (VFI) of clitoral body and labia minora, blood pressure measurement, and hormonal assay. RESULTS: The subjects were divided in: nonsmokers (Group I; N=72); current (>2 years) light smokers-1 to 10 cigarettes/day-(Group II; N=35); and current heavy smokers->10 cigarettes/day-(Group III; N=30). The 2-D Doppler analysis of the ophthalmic and internal carotid arteries showed significant increased resistance in Group III compared with Group II and Group I. The genital vessels (uterine, clitoral, and labium minus arteries) showed the lowest PIs in the nonsmokers. The 3-D power Doppler histogram analysis of clitoral and labium minus blood flow showed the worst vascular indices (VI, FI, VFI) in the heavy smokers. CONCLUSIONS: Cigarette smoking may favor a reduced central and peripheral tissue perfusion with consequent increased risk of cerebrovascular and cardiovascular diseases and with genital vessels stiffness and impaired sexual performances.

Ultrasonographic extended-view technique for evaluation of abdominal fat distribution in lean women with polycystic ovary syndrome.

OBJECTIVE: To estimate whether, by using a new ultrasonographic technique (extended view; XTD view), young lean women with polycystic ovary syndrome (PCOS) have a more android fat distribution in comparison with normally menstruating women with ultrasonographic evidence of polycystic ovaries (PCO) and healthy control subjects, matched for both age and body mass index. DESIGN: Prospective observational study. SETTING: University Hospital. SAMPLE: Forty-nine lean women with PCOS, 42 eumenorrheic women with bilateral PCO and 40 healthy volunteers with regular ovulatory cycles. METHODS: Fasting blood sampling, ultrasonographic and Doppler analyses and blood pressure monitoring. MAIN OUTCOME MEASURES: Medical examination, biochemical and hormonal parameters, ultrasonographic abdominal fat measurements, ultrasonographic evaluation of carotid intima-media thickness and Doppler analysis of ophthalmic artery. An oral glucose tolerance test was performed to analyze glucose, insulin and C-peptide levels. RESULTS: The XTD ultrasonographic preperitoneal area was significantly larger in women with PCOS than in control subjects (p=0.011). The preperitoneal/subcutaneous ratio was significantly higher in women with PCOS (1.1±0.26) compared with women with PCO (0.84±0.13; p=0.05) and control women (0.67±0.13; p<0.001). The mean pulsatility index of ophthalmic arteries was higher in the PCOS women (1.93±0.57) than in control subjects (1.84±0.38; p=0.041). Total cholesterol, triglycerides and LDL cholesterol were significantly higher in women with PCOS than in those with PCO and in control subjects. CONCLUSIONS: Women with PCOS have an android fat pattern correlated with an age-dependent increased risk of cardiovascular diseases.

Gonadotrophin-releasing hormone-antagonists vs long agonist in in-vitro fertilization patients with polycystic ovary syndrome: a meta-analysis.

AIM: This article is a systematic review of the literature to establish whether there is an advantage in the use of GnRH antagonists (Ant) compared to the long agonist protocol (Ago) in patients with polycystic ovarian syndrome (PCOS). MATERIAL AND METHODS: The meta-analysis was conducted using the MIX software with Mantel?Haenszel weighting method and the fixed effect model. RESULTS: Five studies were identified. We analyzed 269 Ant and 303 Ago cycles. Pregnancy rates and the incidence of ovarian hyperstimulation syndrome (OHSS) were analyzed in all five studies, abortion rates were analyzed on three. Pregnancy rates did not differ between the groups: 137/269 (Ant Group) versus 172/303 (Ago Group) (OR: 0.80 CI: [0.57-1.11]). The incidence of OHSS per Ant (13/269) was significantly lower compared to the Ago (35/303) (OR: 0.47 CI: [0.24-0.92]). No difference was found between the two groups in the abortion rate: 10/77 (Ant Group) versus 9/88 (Ago Group) (OR: 1.29 CI: [0.49-3.36]). CONCLUSION: The limited evidence present in literature suggests that in patients with PCOS there is no difference between a long Ago and an Ant protocol in terms of pregnancy and abortion rates. It seems more likely that the use of the Ant may reduce the incidence of OHSS.

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.

PCOS and urethrovaginal space: 3-D volumetric and vascular analysis.

INTRODUCTION: The vaginal orgasm seems to be evocated by the stimulation of the G-spot: a highly sensitive area on the anterior wall of the human vagina. However, the existence of such a spot is controversial. AIM: To evaluate, by the use of three-dimensional (3-D) ultrasonography, the anatomic structures of the urethrovaginal space both in polycystic ovarian syndrome (PCOS) patients and eumenorrheic non-hirsute controls. METHODS: Twenty-three (Group I) PCOS patients and 25 eumenorrheic young women (Group II) were submitted to two-dimensional (2-D) and 3-D ultrasonography and color Doppler analysis of the urethrovaginal space and of the clitoris. MAIN OUTCOME MEASURES: 2-D ultrasonographic evaluation of the ovaries and of the urethrovaginal space; color Doppler evaluation of the ovarian stromal arteries, urethrovaginal main feeding artery, and dorsal clitoral arteries; 3-D volume calculation of the urethrovaginal space, and 3-D power Doppler analysis of the vascularization index; flow index; and vascularization flow index; hormonal evaluation. RESULTS: The vaginal orgasm was present in 13/23 (56%) patients in PCOS Group and in 13/25 (52%) in the controls. The 3-D reconstruction of the urethrovaginal space demonstrated a gland-like aspect with small feeding vessels: "female prostate." The 3-D mean volume of the "female prostate" was significantly higher in Group I (0.48 ± 0.21 mL) than in Group II (0.39 ± 0.19 mL; P = 0.044). The Virtual Organ Computer-aided AnaLys (VOCAL) built mean volume of the "female prostate" was positively correlated with the time since intercourse (r = 0.486; P = 0.032), with the total length of the urethrovaginal space (r = 0.616; P = 0.025) and with the testosterone (r = 0.424; P = 0.048) circulating values. CONCLUSIONS: The presence of the G-spot and its role in vaginal orgasm remains controversial. In Italians, and normal weight PCOS patients the hyperandrogenism seems to result in ovarian stromal and "female prostate" hyperplasia.

3-D volumetric and vascular analysis of the urethrovaginal space in young women with or without vaginal orgasm.

INTRODUCTION: The existence of the G-spot is controversial. AIM: To evaluate, by the use of three-dimensional (3-D) ultrasonography, the anatomic structures of the urethrovaginal space. METHODS: Nineteen (Group I) eumenorrheic young women who experienced, and 20 (Group II) who did not experience a vaginal orgasm underwent two-dimensional (2-D) and 3-D ultrasonography and color Doppler analysis of the urethrovaginal space and of the clitoris during the early follicular phase of the menstrual cycle. MAIN OUTCOME MEASURES: 2-D ultrasonographic evaluation of the urethrovaginal space, and color Doppler evaluation of the urethrovaginal main feeding artery and dorsal clitoral arteries; 3-D volume calculation of the urethrovaginal space, and 3-D power Doppler analysis of vascular indices of the urethrovaginal space and clitoral body (vascularization index, flow index, vascularization flow index); hormonal evaluation. RESULTS: The 3-D reconstruction of the urethrovaginal space demonstrated a gland-like aspect with small feeding vessels. The total length (19.1 + or - 2.7 mm vs. 17.5 + or - 2.1 mm; P = 0.047), measured with 2-D ultrasound, and the 3-D mean volume (0.59 + or - 0.13 mL vs. 0.26 + or - 0.07 mL; P < 0.001) of the structures contained in the urethrovaginal space were significantly higher in Group I than in Group II. The mean time since the last intercourse was 31 + or - 9 hours in Group I and 18 + or - 3 hours (P = 0.033) in Group II. The urethrovaginal space vascularization, the clitoral volume and vascularization, and the circulating hormonal values did not significantly differ among the two groups. The mean volume of the structures contained in the urethrovaginal space was correlated with time since intercourse (r = 0.685; P = 0.021) and with serum testosterone (r = 0.637; P = 0.032) and androstenedione (r = 0.744; P = 0.011). CONCLUSIONS: The structures we observed in the urethrovaginal space have a gland-like aspect and their volume is correlated with both serum androgen concentrations and time since intercourse.

L-arginine plus drospirenone-ethinyl estradiol in the treatment of patients with PCOS: a prospective, placebo controlled, randomised, pilot study.

OBJECTIVE: To verify the effects of a pill containing drospirenone on the surrogate markers of arterial function and to evaluate the possible improvements induced by the addition of L-arginine. DESIGN: A prospective, placebo controlled, randomised, pilot study. SETTING: University of Bologna. POPULATION: Twenty-eight young women with PCOS. METHODS: Random submission to: drospirenone + ethinylestradiol+ a placebo (Group I; n = 15) or drospirenone + ethinylestradiol + oral L-arginine (4 g × 2/daily) (Group II, n = 13). MAIN OUTCOME MEASURES: Medical examination; blood measurement of nitrites/nitrates, biochemical and hormonal parameters; ultrasonographic analysis and colour Doppler evaluation of uterine, stromal ovarian and ophthalmic arteries; analysis of brachial artery flow-mediated vasodilatation; and 24-h ambulatory blood pressure monitoring. The above parameters were evaluated before and after 6 months. RESULTS: The low dose oral contraceptive containing drospirenone favoured a pre-hypertensive state. The L-arginine supplementation increased the circulating levels of nitrites/nitrates and improved the endothelium-dependent vasodilatation counteracting the negative effect of the contraceptive pill. CONCLUSIONS: Although, the present pilot study was conducted in a limited number of patients, it seems that the L-arginine co-treatment may improve the long-term side effects of the pill reducing the risk of cardiovascular diseases.

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.

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.

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.

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.

Isolated premature pubarche: ultrasonographic and color Doppler analysis--a longitudinal study.

Twenty-seven girls with premature pubarche were studied by ultrasonographic and color Doppler analyses to determine the incidence of polycystic ovaries (PCO), to longitudinally assess their evolution, and to search for any hormonal correlation. The girls were submitted to auxological, clinical, and hormonal evaluation, and 21-hydroxylase deficiency was ruled out by an ACTH test. Furthermore, the girls underwent ultrasonographic and color Doppler ovarian and uterine analyses. Among girls with premature pubarche, the prevalence of PCO was 41%. Advanced skeletal maturation, tall stature, and increased hair distribution were constant in these patients. In patients with ultrasonographic and color Doppler evidence of PCO, the ovarian volume, the number of small-sized subcapsular follicles, the stromal echogenicity, and the ovarian stromal vascularization progressively increased during the study. In the whole studied population, ovarian volume correlated with the number of small-sized follicles (r = 0.719; P < 0.0001). Furthermore, a slight and inverse correlation has been found between ovarian volume and ovarian stromal artery pulsatility index (r = -536; P = 0.048). In conclusion, we affirm that PCO are greatly represented among girls with premature pubarche and progressively evolve.

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.

Tibolone, oral or transdermal hormone replacement and colour Doppler analysis: a prospective, randomised pilot study.

OBJECTIVE: To compare the plasma thromboxane, the plasma viscosity and the Doppler flow modifications induced by tibolone and by oral or transdermal continuous combined hormone replacement therapy. METHODS: Forty-two post-menopausal patients underwent either on: oral daily treatment with tibolone (2.5 mg) (Group I; n= 14); or continuous oral administration of 0.625 mg conjugated equine estrogens + medroxyprogesterone 5 mg per day (Group II; n = 14 ); or continuous estradiol transdermal supplementation, at a dose of 50 microg per day, + medroxyprogesterone 5 mg per day (Group III; n = 14 ). The duration of the study was 6 months and the patients were submitted to transvaginal ultrasonographic evaluation of pelvic organs; Doppler analysis of the uterine, internal carotid and ophthalmic arteries; thromboxane and plasma viscosity assays in basal condition, and at 1, 3 and 6 months from the beginning of the study. RESULTS: Although the endometrial thickness increased significantly, there were no cases in which it exceeded the normal range (< or = 5 mm). In all the three groups, the pulsatility index of the uterine, internal carotid and ophthalmic arteries significantly decreased during the therapy showing a reduced impedance since the first month of treatment. Similar variations were observed for the peak systolic blood flow velocity of the internal carotid and ophthalmic arteries. Hormone replacement therapy and tibolone induced a deep, significant and rapid decrease in plasma thromboxane and plasma viscosity levels. CONCLUSIONS: Hormone replacement therapy and tibolone seem to have beneficial effects on vascular and hemorrheological parameters.

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.