Effects of either tibolone or continuous combined transdermal estradiol with medroxyprogesterone acetate on coagulatory factors and lipoprotein(a) in menopause.

BACKGROUND/AIM: The aim of this prospective controlled study was to compare the effects of two therapies for menopause on factor VII (FVII) and hemostatic variables. METHODS: Postmenopausal women were assigned to receive one of the following treatments: transdermal estradiol (TTS E2; 50 microg) combined in a continuous sequential regimen with oral medroxyprogesterone acetate (MPA; 10 mg/day for 12 days) (group A; n = 20), tibolone (2.5 mg/day) (group B; n = 21) or placebo (group C; n = 19). Sixty women completed the 1-year treatment and underwent follow-up examinations after 3, 6 and 12 months. RESULTS: TTS E2/MPA induced various changes in procoagulatory factors. At 12 months, fibrinogen, activated FVII (FVIIa) and coagulative FVII (FVIIc) had increased by 10.7, 12.9 and 3.7%, respectively. Among the fibrinolytic factors, plasminogen and alpha2-antiplasmin increased by 11.3 and 7.2%, respectively. Lipoprotein(a) [Lp(a)] and antithrombin III (ATIII) did not show any significant variation. Tibolone induced some changes toward a more homogeneous antithrombotic profile. Fibrinogen, FVIIa and FVIIc decreased significantly by 7.5, 8.1 and 21.3%, respectively. Plasminogen increased (by 11.8%) and Lp(a) decreased (by 28.4%). ATIII was unchanged with tibolone therapy. CONCLUSION: Our results show that tibolone induces a significant reduction in FVIIc and Lp(a) and a greater enhancement of factors promoting fibrinolysis than the TTS E2/MPA regimen.

Menopause, mild psychological stress and salivary cortisol: influence of long-term hormone replacement therapy (HRT).

OBJECTIVE: Aim of the present study was to examine the adrenocortical activity in basal condition and following a mild stress exposure in long-term HRT-treated menopausal women. Menopausal women, long term users of HRT (14 subjects) were compared both to menopausal women who had never used HRT (14 subjects) and young pre-menopausal women (14 subjects). STUDY DESIGN: Morning and evening salivary cortisol secretion was measured in samples collected twice a day (08:00 in the morning and 08:00 in the evening). Mild stress response was evoked by administration of the Stroop color-word test (CWT). Salivary cortisol was measured immediately before the start, 15, 30 and 45 min after the completion of the test. RESULTS: Menopause appears not to be associated with an impairment of cortisol circadian fluctuation. Long-term use of HRT in menopause attenuated HPA activity either in basal condition or in response to mild stress exposure. With regard to the CWT performance, all menopausal women took significantly longer than young women to perform the test. However, long-term HRT significantly reduced the number of errors made during the test. CONCLUSIONS: The present study suggested that long-term HRT could help menopausal patients to cope with mild stress and to improve mental performances.

[Effects of hormonal replacement therapy on breast density in postmenopausal women]. / Impatto della terapia ormonale sostitutiva in menopausa sulla densità mammaria.

AIM: Recent studies have indicated that conventional hormonal replacement therapy (HRT) is associated with an increase in breast density. The aim of this non randomised prospective study was to evaluate the effects of HRT and Tibolone on breast density in postmenopausal women. METHODS: The study population included 41 healthy women, who were on different HRT regimens and completed their 5-year mammographic follow-up. Before starting HRT, a baseline mammography was performed and repeated at 12-month interval during the follow-up. The patients, 41 healthy postmenopausal women, received 2 different treatments: continuous transdermal estrogen 50 microg/day plus sequential MPA 10 mg/day for 12 days at cycle (21 patients), Tibolone 2.5 mg/day (20 patients). RESULTS: An increase in breast density was present in 25% of women receiving estrogen plus MPA. There was no mammographic breast density increase in Tibolone group; 9.5% of women receiving Tibolone showed reduced breast density. The modifications of breast density were reported during the 1st year of therapy. CONCLUSION: These findings show that different HRT regimens have different effects on breast density. Tibolone does not significantly affect breast density, so it may be a preferable therapy for a larger group of postmenopausal women, including those with a familiar history of breast cancer and those with breast density.

Hysteroscopic findings in postmenopausal abnormal uterine bleeding: a comparison between HRT users and non-users.

OBJECTIVES: The aim of our study was to investigate hysteroscopic findings in a sample of 410 menopausal women (hormonal replacement therapy, HRT users n = 219 and HRT non-users n = 191) and to evaluate the relationship between the presence of intrauterine disease, the use of HRT and the presence of AUB. METHODS: Two hundred and nineteen women on HRT underwent standard office hysteroscopy by means of the Hamou hysteroscope (in 94 cases for abnormal uterine bleeding (AUB) and in 125 cases for periodic endometrium monitoring). One hundred and ninety-one women who had never received HRT were submitted to office hysteroscopy (154 for AUB and 37 for other reasons). RESULTS: Intrauterine diseases are more frequent in patients who do not use HRT (P = 0.02). Endometrial polyps is a frequent disease present in 30% of the sample (23.7% of HRT users and 30.8% of HRT non-users). Myomas were present in 8.7% of all patients examined (6.8% of HRT users and 11% of HRT non-users). Irregular bleeding in menopause is often associated with endouterine abnormalities: in symptomatic patients the frequency of endouterine diseases was 41% while in asymptomatic patients was 28% (P = 0.003). In patients taking HRT (n = 219) endouterine disease is demonstrated in 37% with AUB and in 26% without AUB (P = 0.07). CONCLUSION: Benign intrauterine diseases (endometrial polyps and submucous myomas) are more frequent in postmenopausal women who do not use HRT. In patients taking HRT irregular bleeding is associated with intrauterine diseases; however, the absence of AUB does not exclude the presence of endometrial polyps or myomas.

[Proposal for an informed consent form for hormonal replacement therapy in ambulatory care]. / Proposta di una scheda di consenso informato alla terapia ormonale sostitutiva nella pratica ambulatoriale.

Hormonal Replacement Therapy (HRT) represents a valid therapeutic approach for menopausal symptoms and for the prevention of cardiovascular disease and osteoporosis. Nevertheless, an informed consent, after a complete information, must be obtained from the patient. This procedure is generally adopted in any medical activity, but the modality of the consent in the HRT administration is not well established (verbal or written?, timing of administration?). The authors propose an informed written consent model to be utilized in menopausal centers; this model synthetically informs about HRT benefits and risks and must be red and signed by the patient. The written consent should be explained through a verbal detailed discussion about it, during which the patient's comprehension must be assured. The informed consent procedure should be renewed every year in long term-users. The influence of the HRT informed consent in menopausal centers must be analyzed in particular as far as women compliance is concerned.

Evaluation of the body composition and fat distribution in long-term users of hormone replacement therapy.

The aim of the study was to evaluate the body composition and fat distribution in long-term users of hormonal replacement therapy (HRT). 18 healthy menopausal women, long-term users of HRT (transdermal estradiol 50 microg continuously administered and 10 mg/day of medroxyprogesterone acetate for 12 days/month) and 18 healthy menopausal women, who had never used HRT were included in the study. Age, menopausal age, parity, weight and height (body mass index, weight/height2), and lifestyle habits were similar. Waist and hip circumference, body composition and waist/hip ratio were measured and the results were analyzed. No significant difference was demonstrated in fat and water percentage, and waist/hip ratio. Nevertheless, the waist circumference of long-term HRT users was significantly lower than that of non-users. In conclusion, abdominal fat in long-term HRT users is lower than that of non-users of similar age, menopausal age and body mass index.

[Hormone substitution therapy. Side-effects and compliance of various therapeutic regimens]. / Terapia ormonale sostitutiva. Effetti collaterali e compliance di differenti regimi terapeutici.

BACKGROUND: The aim of this study is to evaluate the tolerability and long-term compliance of four Estrogen Progestin treatments (HRT) for menopause. METHODS: One hundred and ten symptomatic menopausal women were divided into four groups according to therapeutic regimens: A) Estradiol (E2) transdermal treatment 50 micrograms (TTS 50) continuously administered (cont.) plus Medroxyprogesterone Acetate (MPA) 10 mg/die for twelve days a month: 35 women. B) Conjugated Equine Estrogens (CEE) 0.625 mg/die cont. plus MPA for twelve days a month: 25 women. C) Estradiol transdermal 50 micrograms (cont.) plus MPA 2.5 mg/die cont.: 26 women. D) CEE 0.625 mg/die cont. plus MPA 2.5 mg/die cont.: 24 women. RESULTS: Menopausal symptoms were significantly reduced with all treatments. During the first year group C and D patients showed irregular bleeding (group C: 46%, group D: 61%). After 24 months the bleeding frequency was reduced (group C: 11%, group D: 13%). Mastodynia was the more frequent side-effect in particular among women who were utilizing cont.comb. regimens. The total percentage of drop out (D.O.) after 2 years was more than 30% (Group A: 31%, Group B: 33%, Group C: 39%, Group D: 35%). The most frequent reasons for abandoning HRT (79% of all DO) were not linked to therapy side-effects. 19% of DO switched to other hormonal regimens.

Effect of oral and transdermal hormone replacement therapy on lipid profile and Lp(a) level in menopausal women with hypercholesterolemia.

OBJECTIVE: The aim of this randomized clinical study was to evaluate the hormonal replacement therapy (HRT) effect on plasma lipoproteins and Lp(a) profile in 42 menopausal women with primary hypercholesterolemia (total cholesterol > 240 mg/dL). SETTING: University clinic. PATIENTS AND METHODS: 42 hypercholesterolemic menopausal women were randomly assigned to the following groups; (1) transdermal estradiol, 50 micrograms + medroxyprogesterone 10 mg/day for days; (2) conjugated equine estrogens, 0.625 mg/day + medroxyprogesterone acetate 10 mg/day for 12 days; (3) no treatment. At baseline and after 3 and 6 months two blood samples were collected with a 24-hour interval in order to reduce intraindividual and laboratory variability. Serum total cholesterol, HDL cholesterol, triglycerides, LDL cholesterol, and Lp(a) were determined. RESULTS: Total cholesterol and LDL cholesterol significantly decreased after 6 months in both treated groups in comparison to untreated women; HDL cholesterol and triglycerides showed only minimal changes. HRT at the dosage utilized in the study did not seem influence the Lp(a) concentrations after 3 and 6 months. CONCLUSIONS: Both transdermal and oral estrogens at medium dosage have a favorable influence on total cholesterol and LDL-cholesterol level of hypercholesterolemic menopausal women, but Lp(a) remains resistant to manipulation.

[Effect of GnRH analogues on bone density in the vertebral column and the femur]. / Effetto degli analoghi del GnRH sulla densità ossea della colonna e del femore.

The objective of this study was to evaluate the effect on vertebral and femural bone density of the gonadotropin-releasing hormone (GnRH) analog administration. The changes in mineral bone density after 6 months discontinuation of the GnRH analog treatment were also measured. Forty-three premenopausal women with regular cycles and suffering from uterine myomatosis have been selected for the study. Twenty-eight women (group A) were treated with Goserelin 3.2 mg given as a depot every 28 days for 6 months. Fifteen women were treated with 10 mg of medroxyprogesterone acetate (MPA) from day 16 to day 25 of each month for 6 months. Vertebral and femural bone density was measured (by Hologic QDR-X 1000) just before the start of the study, at 6 months of treatment and at 12 months (after 6 months of discontinuation treatment). Significant loss of vertebral bone density was demonstrated in women treated with GnRH analog. After six months of treatment discontinuation bone mineral density did not recover the pretreatment values. Bone femural density showed a not significant decrease in the GnRH analog group. In our experience, the treatment with GnRH analog in premenopausal women induces a reduction in lumbar bone density that is not reversible after the treatment withdrawal; for this reason it would be safe to add at the GnRH analog a therapy which can prevent the bone loss.

Lumbar and femoral bone density in perimenopausal women with irregular cycles.

OBJECTIVE: The aim of the study was to evaluate the impact of irregular cycles on bone mass in perimenopausal women. SETTING: University clinic. PATIENTS AND METHODS: 118 healthy women aged between 45 and 55 years were divided into three groups according to the previous year's menstrual history (premenopause: regular cycles; perimenopause: irregular cycles; early postmenopause: 1-3 years since the last menstrual cycle). Among the perimenopausal group, only women presenting intervals without menstruation longer than 3 months during the year of the study were selected. Bone mineral density of the lumbar spine and of the proximal femur was measured by dual energy X-ray absorptiometry (DEXA) at the start of the study and after 12 months. RESULTS: The serum estradiol level was significantly lower in postmenopausal women and the FSH serum level showed a significant increase in perimenopausal and postmenopausal women in comparison with premenopausal controls. Bone density at L2-L4, femoral neck, greater trochanter, and total femur did not show significant differences at the beginning of the between-group study. Only the density in Ward's triangle was significantly lower in perimenopausal and postmenopausal women. After twelve months the densities of L2-L4, greater trochanter, Ward's triangle, and total femur showed a significant decrease in postmenopausal women in comparison. The perimenopausal group showed a significant decrease in total femur and Ward's triangle density in comparison with premenopausal. CONCLUSION: The occurrence of marked irregularity of menstrual cycles preceding menopause can influence bone mass, in particular at the femoral site.

[Echographic monitoring of the endometrium with a transvaginal probe in the menopause. A clinical study of 185 women in the menopause]. / Monitoraggio ecografico dell'endometrio con sonda transvaginale in menopausa. Studio clinico su 185 donne in menopausa.

The aim of our study was to verify the efficacy of transvaginal ultrasound scanning as an indicator of the endometrial status in healthy menopausal women. One hundred eighty five healthy women in natural menopause were examined by vaginal sonography; the endometrial patterns were analyzed and the influence on it of body weight, menopausal age, and hormonal therapy was considered. The presence of irregular and the endometrial histology were related to the ultrasound findings. 38% of the women assumed estrogen plus progestin replacement treatment since one-two years, for menopausal complaints. 17% of all patients reported irregular bleeding during the last month. The majority of women (90%), regardless of the hormone assumption, presented en endometrial thickness less than 10 mm. 10% of untreated and treated women had an endometrial thickness between 10 and 20 mm. Among the subjects with elevated menopausal age is more frequent the imaging of endometrial layer minor than 5 mm in comparison with women in early menopause. 4% of untreated and 10% of treated women without irregular bleeding had an endometrial thickness higher than 10 mm, while 67% of women with irregular bleeding presented an endometrial layer higher than 10 mm. In treated group all women with endometrial thickness greater than 10 mm had amenorrhoea. 86% of patients had endometrial atrophy detected by biopsy; hyperplastic endometrium or endometrial cancer was not demonstrated. In conclusion, vaginal sonography is a simple and reliable method in the study of the endometrial pattern in healthy menopausal women.

Hormonal and metabolic effects of transdermal estradiol/progestagen administration in postmenopausal women.

OBJECTIVE: To evaluate the effects on hormonal and metabolic variables and bone density of a transdermal system delivering estrogen and progestagen. DESIGN: Twenty-one patients were included in the study and randomly assigned to the following treatments: group A was treated with transdermal 17 beta-estradiol, 50 micrograms/day (Estraderm TTS 50), from the first to the fourteenth day of the cycle and with a transdermal combination of 17 beta-estradiol (50 micrograms/day) and norethisterone acetate (NETA) 250 micrograms/day during the following 14 days; group B was treated with Estraderm TTS 50 from the first to the twenty-eighth day, adding oral medroxyprogesterone acetate (MPA), 10 mg/day, during the final 14 days. DHEAS, testosterone, SHBG, prolactin, gonadotropins, and estrogens were measured in basal conditions and after 6 months' therapy. In the same schedule, lipid patterns (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides), phosphocalcium variables (osteocalcin, calcitonin, parathormone), and bone mineral density were also studied. RESULTS: Both treatments were efficient in reducing menopausal symptoms. An increase of DHEAS (P < .05) and a decrease of FSH and LH (P < .02, < .01, respectively) were observed in group B. No significant modifications in lipid and lipoprotein metabolism were shown in either group after 6 months. The calcium-regulating hormone osteocalcin (BCG) decreased significantly (P < .05) only in group A; calcitonin, parathormone, and bone density were unchanged after treatment. CONCLUSION: Transdermal administration of estrogen plus progestagen reduces menopausal symptoms, but does not induce changes in metabolic variables and hormonal levels (androgens and prolactin).

[Attitudes toward estrogen replacement therapy. Study conducted on a sample population of women attending an ambulatory care center for the treatment of menopause]. / Attitudine nei confronti della terapia ormonale sostitutiva. Studio su un campione di donne afferenti ad un Centro Ambulatoriale per la cura della menopausa.

Hormonal Replacement Therapy (HRT) is the most effective treatment of menopausal disturbances and has an established role in reducing the cardiovascular risk and in preventing the postmenopausal osteoporosis. Nevertheless several reports have evidenced that compliance with hormonal replacement therapy was not as good as expected, and that physician's and women's opinions can strongly influence the HRT choice, and the continuation of HRT use. The aim of this study was to assess the opinions and the expectations of menopausal women toward HRT. PATIENT AND METHODS. We utilized a questionnaire exploring social and affective conditions, and in particular women's opinions and experiences on menopause, hormonal therapy, the possibility of information, the reasons for accepting or refusing hormonal therapy. The questionnaires were administered to 226 menopausal clinic patients (Menopausal age: 2-10 years) in spontaneous menopause. RESULTS. 28% of the women were taking HRT at the time of the survey. Worries about menopause were reported by 27.4% of the group; this percentage was similar in both user and non-user groups. 70% received information on HRT from family doctors, and 63% from mass-media or conversations. 70% believes that the main problem of menopause is osteoporosis, and its prevention represents the most frequent aim that patients feel can be achieved by HRT. 67.5% of the group is afraid that long term treatment can be dangerous, however only 57% asked for detailed information to the doctor. To the question "Are you informed that HRT can reinduce menstrual bleeding?", 57.5% of the patients answered yes; 30% considered it to be a problem. CONCLUSIONS. Our study was carried out in a menopausal clinic and this can influence the answers of the respondents. Most women received some information on HRT, but their knowledge was only partial and did not eliminate the unrational fear of hormone therapy. Although long term use of HRT is to prevent CVD and menopausal osteoporosis, many of our patients specifically asked for treatment to be as short as possible. Women expectations's towards HRT are mainly referred to osteoporosis prevention and treatment: this may be explained by the high frequency of osteoarticular pain found in our patients; nevertheless it is possible that the more rational fear of osteoporosis hides the unconscious fear of a dramatic physical breakdown caused by the menopause. Detailed information to family doctors, to specialists, and to patients along with a further improvement of therapeutic regimens will allow a greater diffusion of HRT, bringing its short and long term benefits to an increasing number of women.

Maternal plasma and milk free cortisol during the first 3 days of breast-feeding following spontaneous delivery or elective cesarean section.

In a view of the increased clinical interest in the presence of hormones in human milk, the objective of this study was to evaluate maternal plasma and milk cortisol levels in early puerperium and their relationship in breast-feeding in women who underwent elective cesarean section or who delivered vaginally. During the first 3 days of breast-feeding, plasma and milk cortisol levels declined significantly both in women who underwent elective cesarean section and in women who had spontaneous deliveries. Moreover, the breast-feeding procedure did not affect maternal plasma and milk hormonal levels, since no differences between the cortisol levels measured immediately before and after morning daily breast-feeding were detected. Furthermore, a very high positive correlation (p < 0.001) was found between plasma and milk cortisol concentrations. Therefore, maternal plasma cortisol levels can be considered a very reliable measure to predict the hormonal concentration in breast milk.

Intranasal salmon calcitonin in postmenopausal osteoporosis: effect of different therapeutic regimens on vertebral and peripheral bone density.

Sixty postmenopausal women were randomly assigned to three types of treatment with intranasal salmon calcitonin (SCT) plus calcium 500 mg daily (group A: 100 IU daily of SCT; group B: 100 IU daily of SCT for alternate cycles of 2 months with a 1-month interval; group C: 100 IU daily of SCT for alternate cycles of 3 months of treatment followed by a 3-month interval) or calcium 500 mg daily alone (control group). Lumbar density significantly decreased in the control group while it maintained the initial value in both continuously or cyclically treated groups. The bone density of the proximal and distal forearm in treated and control groups did not show significant changes after 12 months.

[Contraceptive methods, induced abortion, first sexual intercourse age, in a group of 1635 students of the University of Rome]. / Contraccezione, I.V.G., eta del primo rapporto in un gruppo di studentesse dell'Universita di Roma.

PIP: The authors report some data about contraceptive choice among young women examined in the Preventive Medicine Center of the University of Rome. Menarche age, menstrual cycle, age at 1st sexual intercourse, contraceptive method used, number of abortions, and pregnancies were examined. Moreover, the relationships between age at 1st sexual intercourse and contraceptive method and abortion were considered. Mean age at 1st intercourse was about 17.5 years. Pill and IUD were used by 11% and 5% respectively of the female students. Coitus interruptus was used among 83.3% of the cases. The prevalence of previous abortion was about 12.6%. The menstrual cycle characteristics did not influence the contraceptive choice of these students. Finally, previous abortion or pregnancy influenced contraceptive choice; in fact about 15% and 16.5% of the women with previous abortion performed or pregnancy experienced adopted the pill and IUD as contraceptive methods. (author's modified)^ieng