Mauro Penotti

Effect of soy-derived isoflavones on hot flushes, endometrial thickness, and the pulsatility index of the uterine and cerebral arteries

OBJECTIVE To determine the effect of soy-derived isoflavones on hot flushes, endometrial thickness, and the vascular reactivity of uterine and cerebral arteries. DESIGN Double-blind, randomized, placebo-controlled trial. SETTING Healthy volunteers in an academic research environment. PATIENT(S) Sixty-two postmenopausal women aged 45-60 years attending the Outpatient Menopause Clinic of our gynecological departments. INTERVENTION(S) The patients were administered 72 mg of soy-derived isoflavones or placebo under double-blind conditions. The daily number of hot flushes was recorded in a diary. Endometrial thickness was measured by means of transvaginal ultrasound; the uterine, internal carotid, and middle cerebral arteries were evaluated using Doppler ultrasound. MAIN OUTCOME MEASURE(S) The daily number of hot flushes, endometrial thickness, and arterial pulsatility index (PI). RESULT(S) Both treatments led to a 40% reduction in the number of hot flushes. Soy-derived isoflavones had no effect on endometrial thickness or the PI of the uterine and cerebral arteries. CONCLUSION(S) The daily administration of 72 mg of soy-derived isoflavones is no more effective than placebo in reducing hot flushes in postmenopausal women. It also has no effect on endometrial thickness or the PI of the uterine and cerebral arteries.

Blood flow variations in internal carotid and middle cerebral arteries induced by postmenopausal hormone replacement therapy

OBJECTIVE Our purpose was to clarify the mechanisms by which postmenopausal estrogen replacement therapy exerts its protective effect on cardiovascular risk. STUDY DESIGN By means of a bidirectional Doppler ultrasonographic system we measured pulsatility index variations the internal carotid artery and middle cerebral artery in 25 early postmenopausal women during a 6-month period of hormone replacement therapy. Transdermal estradiol (50 micrograms/day) was continuously administered. A 12-day course of medroxyprogesterone acetate (10 mg/day) was added every second month. RESULTS The pulsatility index showed a significant (p = 0.0001) reduction in both arteries after 6 weeks. At 22 weeks a 25% reduction was measured. No variation of the estrogen-induced pulsatility index reduction was observed at the end of every cyclic progestogen supplementation. CONCLUSIONS In early postmenopausal women hormone replacement therapy causes a rapid reduction of pulsatility index in brain arteries. Cyclical progestational supplementation does not modify this positive effect on reactivity of the blood vessels.

Cerebral artery blood flow in relation to age and menopausal status

Objective To investigate vascular reactivity in womens cerebral arteries from reproductive age to postmenopause. Methods The pulsatility index (PI) was measured cross-sectionally in the internal carotid and middle cerebral arteries of 120 women, using a Doppler ultrasound system. Fifteen women were enrolled in each of eight 5-year intervals, spanning ages 20–59 years. Results In the population as a whole, there was a slight but statistically significant correlation between age and the PI in both arteries, but not after excluding postmenopausal subjects. A significant correlation was found between PI and months since menopause (but not chronologic age) in the postmenopausal women. There was also a statistically significant difference in the PI values for both arteries between pre- and postmenopausal women of similar age. Conclusion Menopause causes a significant increase in the PI of womens cerebral arteries. In postmenopausal women, there is a significant correlation between the PI of the internal carotid and middle cerebral arteries and menopausal but not chronologic age. This effect may be one of the mechanisms by which menopause is associated with the known higher risk for coronary heart disease observed in women.

The effect of tamoxifen and transdermal 17β-estradiol on cerebral arterial vessels: A randomized controlled study

OBJECTIVES Our objective was to study the effects of tamoxifen on cerebral arterial reactivity. STUDY DESIGN We studied the reactivity of both the internal carotid artery and the middle cerebral artery during a 12-month period of administration of either oral tamoxifen or transdermal estradiol or no treatment. A total of 45 healthy postmenopausal women who had undergone hysterectomy were followed up. Patients were randomly allocated to treatment with either oral tamoxifen 20 mg/day or transdermal estradiol 50 microg/day or nothing (15 patients in each group). They all underwent Doppler examinations of the internal carotid artery and middle cerebral artery at the beginning of the study and after 2, 6, and 12 months of treatment. The pulsatility index was measured. RESULTS In the women given transdermal estradiol the pulsatility index of both the internal carotid artery and the middle cerebral artery was significantly reduced compared with that in the controls. Tamoxifen did not induce variations of pulsatility index in either artery during all the study period. The difference between the effect of the two drugs on the pulsatility index of both arteries was highly significant. CONCLUSIONS Our findings demonstrate that tamoxifen does not cause any variation in the pulsatility index of cerebral arteries. The action of transdermal estradiol on the pulsatility index of cerebral arteries in postmenopausal women is the expression of a generalized action of estrogens on arterial vessels, and if this expression plays a role in the protective effect of hormone replacement therapy on risk of cardiovascular disease, tamoxifen treatment in healthy postmenopausal women should be considered with renewed caution.

Gonadotropin releasing hormone agonist therapy and its effect on bone mass

The effects on bone mass of a 6 month therapeutic cycle with a gonadotropin releasing hormone agonist (GnRHa) were studied in 22 patients, ten affected by pelvic endometriosis and 12 by uterine fibroids. All patients were subjected to preliminary full examinations to confirm their diagnosis (laparoscopy for the endometriosis group and precise ultrasound volume measurements for uterine fibroids group). Before the beginning of treatment, bone mineral density (BMD) was measured in each patient both on the distal third of the forearm, with single-photon absorptiometry, and on the lumbar spine (L1-L4), with dual photon absorptiometry. The gonadotropin releasing hormone agonist used was buserelin. In the first week of therapy 0.5 mg of the drug was administered subcutaneously thrice daily. In the following 25 weeks the same drug was given intranasally, at a dosage of 300 micrograms again three times a day. Bone mass measurements, both at the peripheral and at the axial site, were repeated at the end of the 26-week therapeutic cycle and then again 6 months later. At the 26th week, a significant decrease of BMD was observed at both sites. The loss was 1.5% (p less than 0.05) on the lumbar spine, and 2.1% (p less than 0.05) on the radius. No bone mass restoration took place in the following 6 months. On the contrary, a less significant but discernible trend towards a further bone loss was apparent in the BMD values measured 6 months after the end of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Gonadotropin-releasing hormone agonist-induced hypoestrogenism and blood flows in cerebral arteries *

OBJECTIVE To evaluate the effect of the hypoestrogenism induced by GnRH agonist (GNRH-a) therapy on cerebral vessel blood flow. DESIGN Open, controlled study. SETTING Tertiary care units of the University of Milan, Italy. PATIENTS Young women scheduled to undergo 6 months of therapy with a GnRH-a; a control group was also enrolled. INTERVENTIONS In both groups, the pulsatility index of both the internal carotid artery (ICA) and middle cerebral artery (MCA) was measured by means of Doppler ultrasound over a period of 6 months. MAIN OUTCOME MEASURE The ICA and MCA pulsatility index. RESULTS No variation in the pulsatility index of either artery was found in either group. CONCLUSIONS A 6-month period of GnRH-a-induced hypoestrogenism in young women does not lead to any variation in the blood flow of cerebral vessels. This provides some reassurance as to the safety of these drugs in relation to the role that the reactivity of peripheral arteries may play in determining risk of cardiovascular disease. Furthermore, our results show that blood flow in the cerebral vessels of young subjects is under extraestrogenic control and that this may counterbalance estrogen deprivation through mechanisms that probably are no longer active in the perimenopausal years.

Compressive Suture of the Lower Uterine Segment for the Treatment of Postpartum Hemorrhage due to Complete Placenta Previa: A Preliminary Study

Aim: To assess the efficacy of a uterine compression suture technique in controlling hemorrhage after removal of complete placenta previa during cesarean section. Methods: This prospective study was performed in a tertiary referral hospital and included 18 patients with postpartum hemorrhage following removal of complete placenta previa during elective cesarean section. All 18 patients underwent bilateral anteroposterior compression suture of the lower uterine segment. All patients were followed postpartum for evaluation of uterine cavity and menstrual cycles. Results: Anteroposterior compressive suture of the lower uterine segment achieved immediate complete hemostasis in all 18 patients. No surgical complication was observed. All patients recovered normal menstrual cycles. Normal patency of the uterine cavity was documented with sonohysterography in all patients at the 6-month follow-up visit. Conclusions: This quick and simple suture technique seems to be effective in stopping hemorrhage following complete placenta previa removal during cesarean section. Normal patency of the uterine cavity seems not to be impaired at medium-term follow-up.