Factors associated with climacteric symptoms in women around menopause attending menopause clinics in Italy.

OBJECTIVE: To obtain data on correlates of climacteric symptoms in women around menopause attending menopause clinics in Italy. METHODS: Since 1997 a large cross sectional study has been conducted on the characteristics of women around menopause attending a network of first level menopause outpatient's clinics in Italy. A total of 66,501 (mean age 54.4 years) women are considered in the present paper. RESULTS: The odds ratios of moderate and severe hot flashes/night sweats were lower in more educated women and (for severe symptoms only) in women reporting regular physical activity. Depression, difficulty to sleep, forgetfulness and irritability tended to be less frequent in more educated women and (depression only) in women reporting regular physical activity. Parous women reported more frequently these symptoms. CONCLUSIONS: This large study confirms in Southern European population that low education, body mass index and low physical activity are associated with climacteric symptoms. Parous women are at greater risk of psychological symptoms.

Risk factors for type 2 diabetes in women attending menopause clinics in Italy: a cross-sectional study.

OBJECTIVE: To analyze risk factors for type 2 diabetes among women attending menopause clinics in Italy for counselling about the menopause. SUBJECTS: Women attending a network of first-level outpatient menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms. METHODS: Cross-sectional study with no exclusion criteria. Type 2 diabetes was defined according to National Diabetes Data Groups Indications and the fasting blood glucose at an oral glucose tolerance test within the previous year. RESULTS: Out of the 44 694 considered in this analysis, 808 had a diagnosis of diabetes type 2 (1.8%). In comparison with women aged < 50 years, the multivariate odds ratios (OR) of type 2 diabetes were 1.31 (95% confidence interval (CI), 0.99-1.74) for women aged 50-52 years, 1.66 (95% CI, 1.27-2.17) at 53-56 years and 2.84 (95% CI, 2.20-3.67) in women aged > or = 57 years. Type 2 diabetes was less frequently reported in more educated women (OR high school/university vs. primary school = 0.44 (95% CI, 0.36-0.55)). Being overweight was associated with an increased risk of type 2 diabetes. In comparison with women reporting a low level of physical activity, the multivariate OR of type 2 diabetes was 0.67 (95% CI, 0.54-0.84) for women reporting regular physical activity. In comparison with premenopausal women, the multivariate OR of type 2 diabetes was 1.38 (95% CI, 1.03-1.84) in women with natural menopause. This finding was present also after allowing for the potential confounding effect of age. The multivariate OR of diabetes for users of hormonal replacement therapy was 0.58 (95% CI, 0.46-0.73). CONCLUSIONS: This large cross-sectional study suggests that postmenopausal women are at higher risk of type 2 diabetes after allowance for the effect of age. Other main determinants of risk of type 2 diabetes in women around menopause were low socioeconomic status and being overweight. Diabetes was found less frequently in those taking hormone replacement therapy.

Effects of androgen supplementation of hormone replacement therapy on the vascular reactivity of cerebral arteries.

OBJECTIVE: To determine the effect of the androgen supplementation of hormone replacement therapy (HRT) on the vascular reactivity of cerebral arteries. DESIGN: Open randomized study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Forty postmenopausal women who were treated with sequential HRT (transdermal E2 50 microg/d + medroxyprogesterone acetate 10 mg/d for 12 days every other month) for > or =1 year and < or =5 years. INTERVENTION(S): Testosterone undecanoate (40 mg/d, p.o.) was randomly administered to 20 patients during ongoing HRT; the other 20 served as controls. Doppler evaluations of the internal carotid and middle cerebral arteries were performed together with lipid levels assessments. A visual analogue scale (VAS) was used to evaluate various parameters relating to sexual life and well-being. MAIN OUTCOME MEASURE(S): Pulsatility index (PI) of the arteries, VAS assessment of psychophysical well-being. RESULT(S): The administration of testosterone undecanoate during HRT induced an increase in the PI of the middle cerebral artery and a reduction of high-density lipoprotein cholesterol. Sexual desire and satisfaction were greatly improved. CONCLUSION(S): In postmenopausal women, androgen supplementation during HRT can partially counteract the beneficial effects of estrogens on cerebral vascular reactivity and lipid profiles, but sexual desire and satisfaction are greatly improved.

Blood flow in the internal carotid and middle cerebral arteries: effects of continuous oral conjugated equine estrogens administration with monthly progestogen supplementation on postmenopausal women.

OBJECTIVE: This study was designed in order to evaluate the effect of conjugated equine estrogens (CEE) on internal carotid and middle cerebral artery blood flow in postmenopausal women. DESIGN: Thirty-four healthy postmenopausal women with intact uteri were randomly divided into two groups of 17 subjects each. The first group was treated for 24 weeks with continuous CEE medication (0.625 mg daily) and cyclical supplementations of 5 mg/day of medrogestone acetate, given on the last 12 days of every 4-week period (Prempak, Wyeth, Italy). The second group received no treatment. The pulsatility indices (PI) of both the internal carotid artery and middle cerebral artery were measured. RESULTS: In the treated group, the PI of the interior carotid artery and MCA was reduced from respectively 0.736 (0.016) and 0.745 (0.009) at baseline, to 0.669 (0.021) and 0.670 (0.011) after 24 weeks (p = 0.01); in the control group, the PI values remained unchanged. The between-group difference for both arteries was significant (p < 0.01). CONCLUSIONS: The administration of CEE with cyclical medrogestone supplementation to postmenopausal women induces a statistically significant reduction in the PI of cerebral arteries.

The effect of tamoxifen and transdermal 17beta-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.

Alteration in the pulsatility index values of the internal carotid and middle cerebral arteries after suspension of postmenopausal hormone replacement therapy: a randomized crossover study.

OBJECTIVE: The aim of the study was to investigate the effect of the suspension of hormone replacement therapy on blood flow in the internal carotid and the middle cerebral arteries. STUDY DESIGN: Doppler ultrasonography was used to measure the pulsatility index of the internal carotid and middle cerebral arteries of 23 women. The patients were all receiving continuous transdermal estradiol replacement therapy (50 micrograms/day) with a cyclic supplementation of medroxyprogesterone acetate every second month (10 mg/day for 12 days). The duration of the study was 12 months. The patients were randomly assigned to one of two groups. The first group (11 subjects) continued therapy for the first 6 months and then suspended it for the following 6 months; the second group (12 subjects) interrupted hormone replacement therapy for the first 6 months and then resumed it for the following 6 months. The internal carotid and middle cerebral artery pulsatility index was measured at the start of the 12-month period and then every 3 months. Serum estradiol levels were measured to check compliance. RESULTS: A statistically significant difference was found between the internal carotid and middle cerebral artery pulsatility index values of the two groups at each of the measurements after the first one. Over the first 6 months the pulsatility index values rapidly increased in the patients kept off hormone replacement therapy and remained stable in those receiving hormone replacement therapy. After the crossover at 8 months, the pulsatility index rapidly dropped to values similar to those at baseline in the patients who resumed hormone replacement therapy and increased in those who suspended therapy. CONCLUSIONS: Resistance to blood flow in cerebral vessels of postmenopausal women rapidly changes after hormone replacement therapy suspension. In postmenopausal women estrogen administration should be continued to maintain the favourable variations of vascular reactivity induced by hormone replacement therapy.

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.

Cerebral artery blood flow in relation to age and menopausal status.

OBJECTIVE: To investigate vascular reactivity in women's 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 women's 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.

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.

Bone mass measurement by DXA: influence of analysis procedures and interunit variation.

Interunit variability among bone densitometers is due to different factors, including different calibration procedures and algorithms and variability in photon source energies and/or intensities. Other factors, such as the choice of scan parameters or the analysis procedures, can also introduce variability. The new generation of dual-energy x-ray absorptiometry (DXA) has partially improved this situation. The aim of this study was to investigate the operator-dependent analysis procedures that can affect scan results and to evaluate the phantom and in vivo interunit variation of some DXA instruments. Four DXA instruments (QDR 1000 and 1000/W, Hologic, Inc.) were used. Potential sources of variability in the analysis procedures of anteroposterior lumbar spine and hip scans were considered: in most cases these procedures significantly influenced scan results. On lumbar spine, an enlargement of the scan window of less than 3 cm was responsible for an average increase in bone mineral density (BMD) of about 3%. On the hip, lowering the scan window by about 1 cm accounted for an increase in the whole-segment BMD of about 4%. After standardization of analysis procedures, interunit and intraunit coefficients of variation and percentage differences among instruments were less than 1% for all the parameters considered (area and bone mineral content and density) with both an anatomic and a geometric phantom, and in nine subjects scanned by two different devices the percentage difference in BMD was greater than 2%. This study shows that present interunit variability allows comparisons among laboratories, but only if highly standardized analysis procedures are used.

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)

[Evaluation of the cholesterol-lowering effectiveness of pantethine in women in perimenopausal age]. / Valutazione dell'efficacia ipocolesterolemizzante di pantetina in donne in età perimenopausale.

Cardiovascular diseases are the main cause of death also in women. Their incidence, rapidly growing in the peri-menopausal period, is related to serum levels of total cholesterol and its LDL fraction. It was also shown that the peroxidation of LDL is an additional factor in the genesis of atherosclerotic vascular disease. As long-term treatments with synthetic lipid-lowering drugs may cause undesirable side effects, while pantethine is known to be well tolerated, we treated 24 hypercholesterolemic women (total serum cholesterol greater than or equal to 240 mg/dl), in perimenopausal age (range: 45-55 years, mean +/- SD = 51.6 +/- 2.4) with 900 mg/day of pantethine. This is a precursor of coenzyme A, with an antiperoxidation effect in vivo, and our aim was to confirm its lipid lowering activity in this particular type of patients. After 16 weeks of treatment, significant reductions of total cholesterol, LDL-cholesterol and LDL-C/HDL-C ratio could be observed. No remarkable changes of the main laboratory parameters (fasting blood sugar, B.U.N., creatinine, uric acid) were seen. Efficacy percentages of the treatment were about 80%. None of the patients complained of adverse reactions due to the treatment with pantethine. In conclusion, we suggest that pantethine should be considered in the long-term treatment of lipid derangements occurring in the perimenopausal age.

[Transdermal estrogenic therapy in menopause]. / Terapia estrogenica per via transdermica in menopausa.

The availability of percutaneous estrogenic preparations capable of directly entering the bloodstream, avoiding the liver, has opened new prospects in the treatment of the climacteric syndrome. The purpose of our work has been to compare the effectiveness and tolerability of a percutaneous 17-beta-estradiol-oral progestin association with an all oral association of conjugated estrogens and progestins and to evaluate the ability to control menopausal symptoms and biohumoral characteristics. 42 (1 to 7 years postmenopausal) heavily symptomatic patients were selected at the "Centro per lo studio e la terapia del climaterio" in Milan and divided in two equally sized groups. One group was treated using the percutaneous therapy, the other with the all-oral one. The results show that percutaneous administration leads to a quicker control of vasomotor symptomatology and metabolic effects similar to oral administration.