Effects of raloxifene and hormone replacement therapy on markers of serum atherogenicity in healthy postmenopausal women.

OBJECTIVE: To determine the effect of raloxifene (RLX) and hormone replacement therapy (HRT) on non-high density lipoprotein cholesterol (non-HDL-C) levels and the apolipoprotein-B/apolipoprotein-A1 (apo-B/apo-A1) concentration ratio, markers of serum atherogenicity, in postmenopausal women. METHODS: Three hundred and ninety healthy postmenopausal women aged 45-72 years were enrolled in a double-blind, randomized, placebo-controlled, parallel trial at eight outpatient sites in the United States. Women were randomly assigned to receive continuous combined HRT (0.625 mg/day conjugated equine estrogen and 2.5 mg/day medroxyprogesterone acetate), 60 or 120 mg/day raloxifene, or placebo for 6 months. Serum concentrations of non-HDL cholesterol and the apo-B/apo-A1 concentration ratio were measured in serum samples obtained at baseline and at 6 months of treatment. RESULTS: At 6 months, non-HDL-C and apo-B/apo-A1 were significantly reduced by 60 mg/day RLX (10 and 11%, respectively), 120 mg/day RLX (9 and 12%, respectively) and HRT (10 and 12%, respectively), compared with placebo. The effect of all treatments to lower non-HDL-C and apo-B/apo-A1 was greatest in women with hypercholesterolemia (total-C>240 mg/dl) at baseline. Among women with undesirable (>160 mg/dl) non-HDL cholesterol at baseline, RLX and HRT lowered the percentage of these women remaining above this threshold after 6 months (placebo, 89%; 60 mg/day RLX, 61%; 120 mg/day RLX, 74%; HRT, 58%). Similar results were observed for women with high (>190 mg/dl) non-HDL cholesterol at baseline. CONCLUSION: In healthy postmenopausal women, RLX and HRT lower serum non-HDL-C and apo-B/apo-A1, indicators of serum atherogenicity, to a similar extent.

Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation.

Raloxifene, a selective estrogen receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis, has shown a significant reduction in breast cancer incidence after 3 years in this placebo-controlled, randomized clinical trial in postmenopausal women with osteoporosis. This article includes results from an additional annual mammogram at 4 years and represents 3,004 additional patient-years of follow-up in this trial. Breast cancers were ascertained through annual screening mammograms and adjudicated by an independent oncology review board. A total of 7,705 women were enrolled in the 4-year trial; 2,576 received placebo, 2,557 raloxifene 60 mg/day, and 2,572 raloxifene 120 mg/day. Women were a mean of 66.5-years old at trial entry, 19 years postmenopause, and osteoporotic (low bone mineral density and/or prevalent vertebral fractures). As of 1 November 1999, 61 invasive breast cancers had been reported and were confirmed by the adjudication board, resulting in a 72% risk reduction with raloxifene (relative risk (RR) 0.28, 95% confidence interval (CI) 0.17, 0.46). These data indicate that 93 osteoporotic women would need to be treated with raloxifene for 4 years to prevent one case of invasive breast cancer. Raloxifene reduced the risk of estrogen receptor-positive invasive breast cancer by 84% (RR 0.16, 95% CI 0.09, 0.30). Raloxifene was generally safe and well-tolerated, however, thromboembolic disease occurred more frequently with raloxifene compared with placebo (p=0.003). We conclude that raloxifene continues to reduce the risk of breast cancer in women with osteoporosis after 4 years of treatment, through prevention of new cancers or suppression of subclinical tumors, or both. Additional randomized clinical trials continue to evaluate this effect in postmenopausal women with osteoporosis, at risk for cardiovascular disease, and at high risk for breast cancer.

Raloxifene and estrogen effects on quality of life in healthy postmenopausal women: a placebo-controlled randomized trial.

OBJECTIVE: To assess the effects of raloxifene, estrogen, and placebo on quality of life in healthy, asymptomatic, postmenopausal women. METHODS: In a multicenter, double-blind, 12-month study, 398 women were assigned randomly to one of four groups: raloxifene HCl, 60 (n = 97) or 150 mg/day (n = 100); conjugated equine estrogens, 0. 625 mg/day (n = 96); or placebo (n = 105). The Women's Health Questionnaire, a validated quality-of-life instrument for perimenopausal and postmenopausal women, was administered at baseline and 3-month intervals. RESULTS: Overall, quality of life from baseline to end point was preserved equally in all treatment groups. Six domains (depressed mood, somatic symptoms, memory/concentration, sexual behavior, sleep problems, and perceived attractiveness) were unchanged in all groups. Three domains (menstrual symptoms, vasomotor symptoms, and anxiety/fears) were statistically significantly different among groups. Mean scores for menstrual symptoms significantly worsened and vasomotor symptoms significantly improved from baseline to end point in the estrogen group. Mean scores for vasomotor symptoms did not worsen at any point in the raloxifene 60 mg/day group. Mean anxiety/fears scores improved significantly during raloxifene 60 mg/day administration throughout treatment (P <.05), irrespective of previous hormone replacement therapy, baseline estradiol (E2) levels, or years postmenopause. CONCLUSION: Most quality-of-life domains were not affected by treatment with estrogen or raloxifene. Estrogen provided relief from vasomotor symptoms but caused menstrual symptoms. Raloxifene 60 mg/day improved anxiety levels in postmenopausal women.

Selective estrogen receptor modulators: tissue selectivity and differential uterine effects.

Selective estrogen receptor modulators (SERMs) are compounds that bind to estrogen receptors and produce estrogen-like (agonist) effects in some tissues and estrogen-blocking (antagonist) effects in other tissues. One of the goals of SERM research has been to develop compounds that provide the potential benefits of estrogen in the skeleton and cardiovascular system, but avoid the negative effects of estrogen in other tissues. Estrogen therapy has been consistently associated with endometrial stimulation, including glandular proliferation, hyperplasia and cancer. In contrast, the presence or degree of endometrial stimulation observed with SERMs varies by compound. The purpose of this review is to differentiate the endometrial effects of compounds that display a SERM-like profile. Molecular mechanisms involving SERM binding to estrogen receptors, preclinical uterine effects in both tissue culture and animal models, and endometrial findings in clinical experience are discussed. There are several SERMs commercially available or in development. The favorable safety profile of raloxifene in the uterus differentiates it from the others. Future SERM development will continue to focus on finding compounds that exhibit minimal endometrial stimulation.

Videolaseroscopy for oophorectomy.

Laparoscopic oophorectomy was performed on 94 ovaries in 76 patients. Indications included recurrent pain associated with endometriosis and adhesions in 17 patients (18 ovaries), ovarian endometriomas in 40 patients (40 ovaries), prophylactic oophorectomy (breast cancer) in one patient (2 ovaries), removal of the ovaries at the time of laparoscopic assisted vaginal hysterectomy in 15 patients (30 ovaries), and other indications in three patients (four ovaries).

Videolaseroscopy. The CO2 laser for advanced operative laparoscopy.

A specific technique of advanced operative laparoscopy, known as videolaseroscopy, using the CO2 laser and videomonitor, is described. Operating room setup, anesthesia considerations, and specific applications to pelvic disease are elaborated.

Laparoscopic myomectomy.

Laparoscopic myomectomy was performed on 154 women, with minimal perioperative complications resulting. Small and single leiomyomata were managed more easily than multiple and larger tumors. Although suturing the excisional sites improved healing, it increased the incidence of adhesion formation. We conclude that laparoscopic myomectomy can be a safe and cost-effective alternative to laparotomy when performed by a skilled operative laparoscopist, but only in selected cases.

Comparison of direct insertion of disposable and standard reusable laparoscopic trocars and previous pneumoperitoneum with Veress needle.

A randomized prospective study was conducted to evaluate the ease of use and safety of direct insertion of laparoscopic trocars. Comparison of previous pneumoperitoneum by Veress needle insertion with direct insertion of the reusable conventional laparoscopic trocar and direct insertion of the disposable shielded trocar revealed minor complication rates of 22, 6 and 0%, respectively. No major complications occurred in this series of 200 patients.

Laparoscopic ovarian cystectomy during pregnancy.

A pregnant woman with a history of endometriosis and persistent bilateral adnexal masses underwent laparoscopic ovarian cystectomies at 16 weeks of gestation. There were no adverse sequelae, and the patient had an otherwise uneventful pregnancy and delivery. Operative laparoscopy should be considered to replace laparotomy in appropriate cases during pregnancy.

Laparoscopically assisted anterior rectal wall resection and reanastomosis for deeply infiltrating endometriosis.

A 28-year-old woman, presented with a history of long-standing, severe pelvic and bowel endometriosis. Pronounced cul-de-sac tenderness and nodularity were noted on pelvic examination. Videolaseroscopy was undertaken, the rectum was mobilized, and the tumor was prolapsed to the level of the anus. Anterior rectal wall resection and reanastomosis were performed; the colon was returned to the pelvis under direct visualization via laparoscope.

Maternal outcome in class H diabetes mellitus.

The term class H diabetes mellitus has recently been used to describe pregnant diabetic women with ischemic heart disease. In such patients, the risks of abortion may approach those of continuing the gestation. Because significant cardiac disease can occur with diabetes of even recent onset, a baseline electrocardiogram is thus recommended for all pregnant diabetic women. Review of the literature reveals 11 cases, 8 of which resulted in maternal death. The authors have successfully treated a class H diabetic woman who delivered a healthy infant at 36 weeks' gestation.