The lowering of lipoprotein[a] induced by estrogen plus progesterone replacement therapy in postmenopausal women.

OBJECTIVE: To evaluate whether estrogen plus progesterone replacement therapy influences the plasma lipoprotein[a] (Lp[a]) levels in postmenopausal women. DESIGN: Fifty-five women who had been menopausal for at least 1 year were followed up for 12 months. Twenty-four subjects served as the control group and 31 subjects served as the therapy group. The therapy consisted of conjugated estrogen (1.25 mg/d) and medroxyprogesterone acetate (10 mg/d for 10 days a month). Blood samples were obtained before the start of therapy and at 6 months and 12 months after therapy. Nine subjects in the therapy group were followed up for an additional year after the treatment was suspended (washout group). SETTINGS: All subjects were healthy women (mean age, 52 years) who had natural menopause at least 1 year before the beginning of recruitment. None of the women had received exogenous sex steroids or drugs known to influence lipid and lipoprotein metabolism in the previous 12 months. MAIN RESULTS: In the control group, no change was noted in the plasma Lp[a] concentrations during the study. In the treatment group, the mean plasma Lp[a] concentrations decreased 50% after 6 months (P < .01) and remained at this level 12 months after treatment was started. In the washout group, mean plasma Lp[a] levels tended to return to pretherapy values. In addition, estrogen plus progesterone treatment significantly lowered total cholesterol levels by 15% and low-density lipoprotein cholesterol levels by 30%; it increased high-density lipoprotein cholesterol levels by 19%. CONCLUSION: The results suggest that in estrogen plus progesterone-treated postmenopausal women, the lipid profile is improved not only by lowering low-density lipoprotein cholesterol levels and raising high-density lipoprotein levels, but also by lowering plasma Lp[a] concentrations.

The effect of menopause on blood lipid and lipoprotein levels. The Icarus Study Group.

There is increasing evidence from epidemiological studies that exogenous estrogen (hormone replacement therapy) protects against the elevated risk of cardiovascular disease in women after the menopause. However, it is still uncertain whether the postmenopausal decrease in endogenous estrogen in itself contributes significantly to this increase in risk. Most of the studies that have provided evidence linking cardiovascular disease with menopause have involved North American women, who may differ significantly from Europeans in terms of lifestyle and diet. ICARUS (Italian Climacteric Research Group Study) is an observational study that involves Italian Menopause Clinics, with the objective of collecting observational data on menopause and its management. The results of a cross-sectional analysis of 9309 women, free from any hormonal treatment and enrolled up to March 1997, are reported here. Data show that the menopause has a marked effect on the circulating levels of lipids and lipoproteins. From pre- to post-menopause there are significant increases in total cholesterol (6.9% before and 4.4% after adjustment for covariates including chronological age, educational level, center, BMI, smoking habits, hypertension and diabetes, previous contraceptive use, and time since menopause), LDL (7.5% before, 4.0% after), and triglycerides (9.0% before, 3.2% (ns) after). However, there is no significant change in HDL. Among postmenopausal women, no effect on lipid profile of time since menopause was observed.

Effects of oral and transdermal hormone replacement therapy on lipoprotein(A) and lipids: a randomized controlled trial.

OBJECTIVE: Our purpose was to compare the effect of oral and transdermal hormone replacement therapy on lipoprotein(a) and other plasma lipids in healthy postmenopausal women. DESIGN: A total of 120 postmenopausal women were enrolled in a prospective randomized controlled study, and allocated either to transdermal 17 beta-estradiol (50 micrograms/day) or to oral conjugated estrogen (0.625 mg/day). Forty-one age-matched women were used as the reference group. Plasma lipids and lipoproteins were determined every 3 months and differences were sought by statistical analysis. RESULTS: Plasma lipoprotein(a) dropped after 3 months of treatment either with transdermal estradiol (p < 0.01) or oral estrogen (p < 0.01). Lipoprotein(a) was reduced by 12% and 22%, respectively. No further decreases were seen later on. Plasma total and low-density lipoprotein (LDL) cholesterol concentrations were decreased significantly with both treatments after 3 months of therapy. No difference was seen in the lowering effect on lipoprotein(a), LDL and total cholesterol concentrations between regimens. Plasma high-density lipoprotein (HDL) cholesterol and triglyceride concentrations increased throughout the study only in patients treated with oral estrogen. CONCLUSIONS: These data demonstrate that hormone replacement therapy reduces the concentration of lipoprotein(a) when given both orally and transdermally. The lowering effect is achieved quickly because the maximal effect is observed after 3 months of therapy.

Lipoprotein(a) and other lipids after oophorectomy and estrogen replacement therapy.

OBJECTIVE: To assess the effect of surgical menopause and subsequent estrogen replacement therapy (ERT) on lipoprotein(a) [Lp(a)] and common lipids. METHODS: In 24 healthy premenopausal women, lipids (total cholesterol, low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, and triglycerides) and gonadotropins (FSH, LH) were measured the day before hysterectomy with bilateral oophorectomy and then after 1, 2, and 3 months. Blood was also drawn after 2, 4, 6, and 15 days to exclude the effect of surgery on Lp(a). In 19 women who volunteered for ERT, the lipid profile was assayed again after 3, 6, and 12 months of treatment. RESULTS: Lipoprotein(a) levels rose significantly over the 3 months after surgery, from a mean +/- standard deviation (SD) 5.7 +/- 6.1 mg/dL to 10.4 +/- 9.2 mg/dL. Total cholesterol and LDL cholesterol levels increased significantly over the first 2 months; HDL cholesterol decreased significantly during the 3 months of follow-up (by 10, 17, and 20%) (P < .001). Plasma triglycerides did not change after surgery. Three months following ERT, Lp(a) and total cholesterol were significantly decreased (28 and 11%, respectively), as was LDL cholesterol (33%) after 6 months. High-density lipoprotein cholesterol increased by 24% after 6 months of treatment, and triglycerides rose significantly in the year of therapy (37%). CONCLUSION: These findings suggest that surgical menopause induces atherogenic changes in the lipid profile in 3 months and that ERT soon reverses them.

Hormonal agents used in lowering lipoprotein(a).

Lipoprotein(a) (Lp(a)) plasma concentrations in Caucasian populations are classified as a quantitative genetic trait. Although the prevailing view has been that Lp(a) levels are affected by age and gender, recent data are beginning to indicate otherwise. Lp(a) levels change throughout life especially in females after menopause. Lp(a) levels decrease in women treated with anabolic steroids such as stanozolol and danazol. The Lp(a) plasma concentration is also profoundly affected by sex hormone variations during pregnancy. In men with prostatic cancer Lp(a) levels are reduced about 50% by estrogen therapy, and increased 20% by orchidectomy. We have evaluated the changes in Lp(a) and lipid levels in postmenopausal women following estrogen/progestogen replacement therapy. The mean level of Lp(a) in treated women was about 50% lower after 6 and 12 months of replacement therapy. A significant correlation between basal Lp(a) levels and the changes at either 6 or 12 months was observed, suggesting that therapy was particularly efficacious in those women with high basal Lp(a) levels. One year after therapy cessation, Lp(a) concentrations tended to return to pre-therapy values. In addition estrogen-progestogen treatment significantly lowered total-cholesterol (12%) and LDL-cholesterol (28%), and increased HDL-cholesterol (18%). From these studies it appears that sex hormones are actively involved in the modulation of plasma Lp(a) levels and that both female and male sex hormones possess a lowering effect. The results confirm a direct effect of sex hormones on Lp(a) metabolism and suggest that estrogen-progestogen treatment of postmenopausal women can improve the lipid profile not only by lowering total- and LDL-cholesterol and raising HDL cholesterol, but also by lowering plasma Lp(a).

Determinants of age at menopause in Italy: results from a large cross-sectional study. ICARUS Study Group. Italian Climacteric Research Group Study.

OBJECTIVE: To identify the determinants of age at menopause in an Italian population, using data from the Italian Climacteric Research Group Study (ICARUS). METHODS: ICARUS is a prospective study of the effect of menopause on women's health that has been running in menopause clinics throughout Italy since 1995. A total of 4300 women with spontaneous menopause, aged 55 years or more and observed for the first time at the participating centres are included in the present analysis. RESULTS: The mean age at menopause in the total population was 50.9 years. After taking into account potential covariates, the women reported smoking, had a slightly lower mean age at menopause than non smokers 50.4 versus 50.9 years; P = 0.01. The mean age at menopause in nulliparae was 50.0 years, and, respectively 50.4, 50.6, 50.9, 51.2 and 50.9 years in those reporting 1, 2, 3, 4 and 5 or more births (P < 0.01). A low body mass index and an early age at menarche were associated with early menopause in the crude analysis, but these associations disappeared after taking into account the confounding factors. CONCLUSIONS: This study offers an estimate of the mean age at menopause of women attending menopause clinics in Italy, on the basis of the data obtained from a large sample. It also indicates that smoking and nulliparity are associated with early menopause.

Efficacy and tolerability of Estraderm MX, a new estradiol matrix patch.

OBJECTIVES: To assess the efficacy and tolerability of a new matrix patch delivering 0.05 mg estradiol per day (Estraderm MX 50) in postmenopausal women with moderate to severe postmenopausal symptoms. METHODS: A multicenter, double-blind, randomized, between-patient, placebo controlled trial in 109 postmenopausal women was carried out. Patches were applied twice weekly for 12 weeks. Patients were assessed at 4, 8 and 12 weeks of treatment. The primary efficacy variable was change from baseline in mean number of moderate to severe hot flushes (including night sweats) per 24 h during the last 2 weeks of treatment. Other variables included Kupperman Index, local and systemic tolerability. Plasma concentrations of estradiol (E2), estrone (E1) and estrone sulfate (E1S) were determined before and after treatment. RESULTS: Estraderm MX was significantly superior to placebo (P < 0.001) in reducing mean number of moderate to severe hot flushes (including night sweats) per 24 h after 4, 8 and 12 weeks of treatment. The estimate of treatment group differences after 12 weeks was 4.2 hot flushes (95% confidence interval: 2.6-5.8). Estraderm MX also significantly reduced Kupperman Index at all time points compared to placebo (P < 0.001). Estraderm MX induced increases in mean E2, E1 and E1S plasma levels as expected (E2: baseline 2.7 pg/ml, 12 weeks 38.9 pg/ml; E1: baseline 18.8 pg/ml, 12 weeks 41.6 pg/ml; E1S: baseline 235.6 pg/ml, 12 weeks 765.1 pg/ml). Overall rates of adverse experiences were similar for Estraderm MX and placebo. The number of patients reporting skin irritation was low and similar in both groups. CONCLUSIONS: Estraderm MX 50, a new matrix patch, offers an effective and well tolerated dosage form for transdermal delivery of 0.05 mg E2 per day.

Effect of hormone replacement therapy and calcitonin on bone mass in postmenopausal women.

A total of 104 postmenopausal women were randomly assigned to different therapeutic regimens: (a) calcitonin, (b) estrogen/progestogen (HRT) plus calcitonin, (c) estrogen/progestogen (HRT), (d) and the control group. The bone mass of the lumbar vertebrae of all patients was assessed with a dual beam photon absorptiometer (Norland GD 153). The 73 patients who completed the 1-yr study showed that postmenopausal bone loss could be prevented by either estrogen/progestogen (HRT) or calcitonin. In addition, the combination of hormonal replacement therapy and calcitonin not only prevented post-menopausal bone loss but resulted in a significant 10% gain in bone mass (P < 0.001).

Reproductive factors, family history, occupation and risk of urogenital prolapse.

OBJECTIVE: We conducted a case-control study to analyze risk factors for urogenital prolapse requiring surgery. METHODS: Cases were 108 women with a diagnosis of II or III degree uterovaginal prolapse and/or third degree cystocele. Controls were 100 women admitted to the same hospitals as the cases, for acute, non-gynecological, non-neoplastic conditions. RESULTS: Occupation showed an association with urogenital prolapse: in comparison with professional/managerial women, housewives had an odds ratios (OR) of urogenital prolapse of 3.1 (95% confidence interval (CI), 1.6-8.8). Compared with nulliparae, parous women tended to have a higher risk of genital prolapse (OR 2.6, 95% CI 0.9-7.8). In comparison with women reporting no vaginal delivery, the ORs were 3.0 for women reporting one vaginal delivery (95% CI 1.0-9.5), and 4.5 (95% CI 1.6-13.1) for women with two or more vaginal deliveries. Forceps delivery and birthweight were not associated with risk of prolapse after taking into account the effect of number of vaginal deliveries. The risk of urogenital prolapse was higher in women with mother or sisters reporting the condition: the ORs were, respectively, 3.2 (95% CI 1.1-7.6) and 2.4 (95% CI 1.0-5.6) in comparison with women whose mother or sisters reported no prolapse. CONCLUSIONS: Our data support the clinical suggestion that parous women are at a higher risk of prolapse and the risk increases with number of vaginal deliveries. First-degree family history of prolapse seems to increase the risk of prolapse.

GnRH agonists before surgery for uterine leiomyomas. A review.

OBJECTIVE: To clarify whether preoperative treatment with gonadotropin-releasing hormone (GnRH) agonists offers substantial advantages to patients undergoing conservative or definitive surgery for uterine leiomyomas. STUDY DESIGN: A review of data from the most recent English-language literature. RESULTS: Inducing amenorrhea in patients with heavy menorrhagia and severe sideropenic anemia before both conservative and definitive surgery for uterine fibroids raises hemoglobin and hematocrit values to within the normal range, limits homologous blood transfusions and enables operations to be scheduled with the patients in better condition. A temporary 30-50% reduction in mean uterine volume theoretically may convert an abdominal into a vaginal hysterectomy in "borderline" cases or sometimes allow a transverse instead of longitudinal abdominal incision. No trial has yet demonstrated "clinically" significant reductions in operating time, operative blood loss or postoperative morbidity in patients undergoing myomectomy or hysterectomy after a course of GnRH agonists as compared with those operated on immediately. There seems insufficient scientific evidence to justify the routine use of GnRH agonists before myomectomy at laparotomy, except possibly in the case of extremely bulky uteri. GnRH agonist treatment before hysteroscopic myomectomy induces endometrial thinning, reduces bleeding and mucous debris, and decreases the diameter of submucous leiomyomas, improving visibility and limiting operating time and fluid intravasation. CONCLUSION: The available data seem to support the use of GnRH agonist treatment before surgery for uterine leiomyomas in selected circumstances. Administration of GnRH agonist for only two or three months preoperatively seems to achieve all the advantages of this treatment, limiting side effects and cost.

[The injectables in urogynecology]. / L'utilizzo di iniezioni periuretrali in uroginecologia.

The purpose of this review is to summarize the results of reports of injectable agents for the treatment of female urinary stress incontinence. The real indication for injectables is intrinsic shincter deficiency (ISD) but urethral hypermobility is not a controindication. Six agents were reviewed: Teflon, autologous fat, collagen, silicone microparticles, silicone microballoons and pyrolytic carbon. Collagen was the most frequently reported agent and yielded 1 year cure/ improvement rate of 60-80%, but results de-creased significantly with longer term follow-up. Teflon has been used longer for the treatment of stress incontinence but both low long and short-term success rate and the reported complications such as particles migration have resulted in its lack of widespread acceptance. Autologous fat has been suggested as the natural injectable but yielded disappointing success rate. Injection of silicone microparticles was associated with a long-term success rate of about 70% in patients with ISD. Moreover, it is now injected without urethroscopy and this makes the procedure easier. Silicone microballoons and pyrolytic carbon have been recently introduced into clinical practice with a short-term success rate of about 70%. However, longer follow-up is needed. In conclusion, long-term durability, cost effectiveness and some safety issues still have to be addressed by further clinical trials.

[Multicenter study on the effectiveness of Tension Vaginal Tape (TVT) in the treatment of stress urinary incontinence]. / Studio multicentrico sull'efficacia del Tension Free Vaginal Tape (TVT) nella terapia della incontinenza urinaria da sforzo.

BACKGROUND: The aim of the study was to evaluate the efficacy of Tension Free Vaginal Tape (TVT) for the surgical treatment of stress urinary incontinence. METHODS: The design was an open multicenter study including six Italian hospitals. Between January 1998 and November 1999, 429 stress incontinent women were enrolled in the study. Before surgery subjects had been studied through their history, urine culture, physical examination, cotton swab test, cough provocation test and urodynamic evaluation including: uroflowmetry, water cystometry and urethral profilometry. Incontinence inconvenience has been quantified through a 10-grade visual analogue scale (VAS). Postoperatively patients were assessed after 6, 12 and 24 months. RESULTS: The mean age of the patients considered was 57 years (range 31-83) and 78 of them had undergone a previous operation for the treatment of stress urinary incontinence or genital prolapse. Out of the 429 patients, 371 were followed for a minimum of 6 months, 11 were lost to follow-up and 47 had been operated recently. After surgery 355 subjects (96%) were subjectively cured and no leakage of urine was observed in 97% of the patients during the postoperative cough provocation test. CONCLUSIONS: This study carried out on a great number of patients demonstrates that TVT is a safe and effective procedure for the treatment of stress urinary incontinence.

Hysterectomy for benign gynecologic disorders: when and why?

Controversy continues to swirl around hysterectomy-particularly about when and why it is appropriate for benign disorders. In the United States, one woman in three undergoes hysterectomy by age 65. The rate in the European Union nations ranges from 6% to 20%. In this review, the most recent epidemiologic data on hysterectomy are summarized, and the generally accepted indications for this procedure for benign gynecologic diseases are presented and discussed.

Sustained prolactin release associated with precocious ovarian failure.

Five women after precocious menopause and 1 patient with primary ovarian failure showed a simultaneous elevation of plasma gonadotropin and prolactin. The hypersecretion of plasma prolactin was still present 6 months after ovarian failure. After 12-18 months of observation while FSH and LH concentration remained elevated, prolactin concentrations normalized in 5 women and decreased in 1.

Bowel perforation during insertion of tension-free vaginal tape (TVT).

A 56-year-old non-obese woman with a previous history of pelvic surgery underwent an uneventful TVT procedure for the treatment of genuine stress incontinence. Postoperatively she began to report an acute low abdominal pain and a secondary laparoscopy was performed. The view of the right iliac region showed the tape passing through a loop of the small intestine. The tape was cut in its intraperitoneal portion and the ileum freed and repaired. After the operation the patient recovered well and was discharged on the fifth day after laparoscopy. Despite the section of the tape, 1 year later the patient is objectively cured by the procedure.

Injection therapy for the treatment of stress urinary incontinence in women.

The purpose of this review is to summarize the results of reports on injectable agents in the treatment of female stress urinary incontinence. Six agents were reviewed: Teflon; autologous fat; collagen; silicone microparticles; silicone microballoons, and pyrolytic carbon. Collagen was the most frequently reported agent and yielded a 1-year cure/improvement rate of 60-80%, but results worsened significantly with longer follow-up. Teflon has been used longer in the treatment of stress incontinence, but low long- and short-term success rates and reported complications such as particle migration have prevented its widespread acceptance. Autologous fat has been suggested as a natural injectable but its success rate has been disappointing. The injection of silicone microparticles is associated with a long-term success rate of about 70% in patients with intrinsic sphincter deficiency, and it can now be injected more easily without the need of urethroscopy. Silicone microballoons and pyrolytic carbon has recently been introduced into clinical practice with a short-term success rate of about 70%, but longer follow- up is needed. In conclusion, the long-term durability, cost-effectiveness, and some safety issues still have to be addressed by further clinical trials.

Gonadotrophins and prolactin rise after bilateral oophorectomy for benign conditions.

The aim of this study was to analyse the changes in follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin concentrations in the 3 months following oophorectomy in pre-menopausal women operated on for benign gynaecological conditions. Included in this analysis were 21 women (mean age 47 years, range 46-52) who underwent bilateral oophorectomy plus hysterectomy for fibroids or ovarian cysts. Plasma concentrations of FSH, LH and prolactin were measured before and on days 2, 4, 6, 14 and 30 after surgery; in 10 cases measurements were made on day 60, and in five cases on day 90 after surgery. Hormone concentrations were measured in duplicate daily samples, and immunoenzymatic assay kits were used for all the immunoassays. The FSH and LH concentrations increased constantly after surgery. Mean prolactin concentrations also increased from 12.1 ng/ml before surgery to 31.5 ng/ml on day 14 after bilateral oophorectomy, but decreased thereafter to 18.2 ng/ml on day 30, 10.9 ng/ml on day 60 and 6 ng/ml on day 90. In conclusion, transient (2-3 weeks) increased prolactin concentrations are observed after surgical castration.

A clinical trial on the effects of a combination of elcatonin (carbocalcitonin) and conjugated estrogens on vertebral bone mass in early postmenopausal women.

The study was carried out to determine the effect of a combination regimen of a small dose of calcitonin added to conjugated estrogens with medroxyprogesterone acetate on vertebral bone mass in early postmenopausal women. Comparisons were made with groups of women on calcitonin alone, on conjugated estrogens with medroxyprogesterone acetate alone, or on no treatment. The study was carried out over a 2-year period. The results of the study suggest that the combined regimen of calcitonin and estrogens increased vertebral bone mass in early postmenopausal women to a greater extent than calcitonin alone or estrogen alone. Increases in vertebral bone mass of 11.2% after 1 year and 9.2% after 2 years were demonstrated using the combined regimen. Both estrogens alone and calcitonin alone were, however, very effective in preventing rapid bone loss in the postmenopausal women studied.

Gonadotropin releasing hormone agonist treatment before hysterectomy for menorrhagia and uterine leiomyomas.

OBJECTIVE: To investigate the effect of gonadotropin releasing hormone agonist (goserelin) treatment before hysterectomy for leiomyomata-associated menorrhagia. DESIGN: Prospective, comparative, nonrandomized study. SETTING: A teaching hospital of Milano University. PATIENTS: Anemic women requiring hysterectomy for myoma-associated menorrhagia. INTERVENTION: Six months' preoperative goserelin treatment (41 cases) or immediate surgery (92 controls). MAIN OUTCOME MEASURES: Abdominal/vaginal hysterectomy rate, number of transfusions, operating time, blood loss, complications, febrile morbidity, and days in hospital. RESULTS: In the goserelin group mean hemoglobin rose (8.5 versus 13.3 g/dl) and mean uterine volume decreased (528 versus 251 ml). At preoperative pelvic exploration abdominal hysterectomy was indicated in 22 (54%) cases and 74 (80%) controls and vaginal hysterectomy in 19 (46%) and 18 (20%) (relative risk 3.6, 95% confidence interval 1.6 to 7.7; p = 0.001). No case required a transfusion whereas 51% of controls needed a total of 127 packed red cell units. CONCLUSIONS: In anemic women with menorrhagia and leiomyomas, gonadotropin releasing hormone agonist treatment before hysterectomy limited transfusion requirements and increased the vaginal procedure rate.