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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.

Objectives: To evaluate the effects of transdermal hormone replacement therapy (HRT) on some biological cardiovascular risk factors, specifically thromboxane B2 level and plasma viscosity. Furthermore, we investigated Doppler flow modifications at the level of the uterine, internal carotid, ophthalmic and bladder wall arteries, and evaluated whether there were significant differences, in the examined parameters, between postmenopausal women who were non-smokers and heavy smokers., Methods: Forty-three postmenopausal women (age 53.6 +/- 3.3 years, mean +/- standard deviation) participated in the study and were divided into two groups (Group I: n = 21, normal controls; and Group II: n = 22, heavy smokers). Patients were treated with continuous estradiol transdermal supplementation and 12-day courses of medroxyprogesterone acetate every 2 months. They were studied at baseline and after 6 months (in the estrogen-only phase of the cycle)., Results: Results showed a beneficial effect of hormone substitution after 6 months of therapy. Plasma viscosity decreased significantly after 6 months of therapy both in non-smokers and heavy smokers (-18% and -14%, respectively). Plasma levels of thromboxane B2, which were similar at baseline, underwent a dramatic reduction in both Group I and Group II (-93% and -88%, respectively). Doppler assessment of pulsatility index at the level of the uterine, internal carotid, ophthalmic and bladder wall arteries showed a significant reduction in vascular impedance at the end of treatment in both groups. However, the treatment was significantly less beneficial, in terms of the analyzed factors, in heavy smokers., Conclusions: Cigarette smoking represents a cardiovascular risk factor that can only partially be modified by the administration of transdermal HRT.

Objectives: To assess differences in two sequential combined hormone replacement therapy (HRT) products on selected cardiovascular and breast metabolic markers. The products were different concerning the route of administration of estradiol and its combined progestin, either oral or transdermal, and the androgenic properties of progestogens, respectively, dydrogesterone and norethisterone acetate., Methods: One hundred and nineteen healthy non-hysterectomized postmenopausal women were included in this open, multi-center, two parallel group trial. They were randomized to a treatment of six 28-day cycles with oral estradiol sequentially combined with dydrogesterone (oE2/D10) or a sequential combination patch of estradiol plus norethisterone acetate (tdE/NETA). At baseline and after six cycles the high-density lipoprotein cholesterol (HDL-C), the sex hormone binding globulin (SHBG) and the total insulin-like growth factor-I (IGF-I) blood levels were determined by a central laboratory. A total of 89 women were compliant to the protocol., Results: After six cycles, a statistically significant difference (P<0.001) concerning HDL-C, SHBG and IGF-I levels was found between the two treatment groups. The HDL-C levels were increased in the oE2/D10 group and decreased in the tdE/NETA group, with a final difference of about 0.3 mmol/l. The oE2/D10 treatment induced a sharp increase (about 57 mmol/l) in SHBG levels. IGF-I levels decreased with both the products, but the difference in favor of the oE2/D10 treatment was of about 30 ng/ml. Moreover, patients on tdE/NETA with an IGF-I baseline value below the median showed an increase., Conclusion: Oral estradiol sequentially combined with dydrogesterone, a non-androgenic progestogen, induced positive changes of some cardiovascular (HDL-C) and breast (SHBG and IGF-I) metabolic markers. These effects were significantly different from those obtained with a transdermal estradiol associated to an androgenic progestogen.

Objective: A controlled 4-year follow-up study was conducted on a population composed of 112 healthy early postmenopausal women to evaluate the ability of ultrasound technology in detecting the effects of hormone replacement therapy (HRT) on bone. At the end of the study, 47 untreated and 25 treated women had been evaluated. Cyclic sequential estrogen/progestogen therapy, 50 microg/day of transdermal 17beta-estradiol (Rotta Research Laboratorium) plus 5 mg/day of medrogestone (Wyeth-Ayerst) was used., Design: Ultrasound transmission through the distal metaphysis of hand phalanxes was measured by DBM Sonic. Beside amplitude-dependent speed of sound (AD-SoS), three new parameters could be calculated: pure speed of sound (pSOS), bone transmission time (BTT), and ultrasound bone profile index (UBPI). Ultrasound measurements were taken at baseline and after 1, 2, and 4 years., Results: Among untreated women a significant decrease of all ultrasound parameters was observed at follow-up measurements. In the HRT-treated group we observed a significant increase of AD-SoS, pSoS, and BTT. We qualified as "responders" women in the treated group for whom AD-SoS, pSoS, and BTT increased by more than 2.77 times the coefficient of variation of the measurement, i.e., 95% variability. Women in the treated group were identified as responders at 4 years of follow-up by AD-SoS (56%), pSOS (56%), and BTT (60%). Ultrasound bone profile index declined in both groups, although to a lower extent among HRT-treated subjects., Conclusions: The 4-year data confirm the results obtained at 1 and 2 years of follow-up. This study demonstrates that bone tissue investigation by ultrasound at the phalanx can be used to monitor the effect of HRT, and thus it should be considered a potential technology for the management of menopause by gynecologists.

Two estradiol (E2) transdermal patches releasing 25 micrograms/day E2 (D-25) or 37.5 micrograms/day E2 (D-37.5) were compared to a placebo patch on 156 patients in natural or surgical menopause suffering from at least 5 hot flushes per day, randomly and blindly assigned to three parallel groups of 52 patients each, to be treated continuously for 12 weeks, without progestin opposition. "Responders" (patients with less than 3 hot flushes per day at the end of treatment), were 82% and 90% under D-25 or D-37.5, respectively, both significantly (p < 0.001) more than under placebo (44%). Comparable efficacy was observed on severity of hot flushes, Kupperman Index and on the self-rated efficacy. Systemic adverse events occurred in 10%, 10% and 8% of patients, respectively, under D-25, D-37.5 or placebo. Occasional mild and transient itching and/or erythema on the site of application was reported by few patients and did never require discontinuation of application. In conclusion D-25 and D-37.5 were significantly more effective than placebo in relieving climacteric symptoms and were systemically and locally as well tolerated as placebo. D-25 (Demestril 25) releasing 25 micrograms/day E2 can therefore be recommended for low-dosed estrogen replacement therapy.

Objectives: To evaluate the effectiveness of transdermal oestrogen replacement therapy plus medrogestone (HRT) in postmenopausal bone loss prevention by means of US., Methods: We enrolled 112 healthy postmenopausal women in an open, prospective study. These women, after a gynaecological evaluation and an US assessment of the skeletal status, were advised to take cyclic sequential oestrogen/progestagen therapy: 50 microg/day of transdermal 17beta-oestradiol (Rotta Research Laboratorium) plus 5 mg/day of medrogestone, for 12 days per cycle (Wyeth-Ayerst). After 1 year we recalled these women: only 32 of them were taking HRT, while 49 had declined HRT without taking alternative therapies. The remaining women were excluded from the study as they were either unavailable for the check-up or they were taking prohibited therapies. We used DBM Sonic 1200 (Igea, Italy) to assess US parameter changes at phalanxes at enrollment and after 1 year. This device enabled us to evaluate US transmission velocity (AD-SoS) and US attenuation pattern (UBPS). In a previous study we had evaluated the intra- and inter-observer reproducibility of AD-SoS measurements (0.4 and 1.0% respectively). Using the same data we evaluated the intra- and inter-observer precision of UBPS., Results: The UBPS intra-operator reproducibilities were 5.3% and 6.1% (for the 1st and the 2nd operator, respectively), while inter-observer precision was 8.8%. Both AD-SoS and UBPS significantly decreased in the non-user group(-0.7%, P < 0.001 and -14.3%, P < 0.001 respectively). In the user group AD-SoS showed a significant increase (+0.7%, P < 0.01), while a slight but significant decrease was observed for UBPS (-2.8%, P < 0.05)., Conclusions: Our findings show that the effectiveness of transdermal HRT in slowing or even arresting postmenopausal bone loss can be monitored by quantitative US studies. The trend difference observed between AD-SoS and UBPS with and without therapy is at least partially explained by a different response to HRT with regard to bone density as well as structure.

The Authors have determined the concentrations of Testosterone, 17beta-oestradiol, FSH and LH by of radioimmunologic assay in blood of seventy normal adult men blood drawn between eight and eleven a.m.) and in blood of thirteen normal adult men blood drawn at eight and twelve a.m., four and eight p.m.). Average values under basal conditions, and circadian variations have been discussed and confronted with those obtained by other authors.