Isaac Schiff

Effects of Postmenopausal Estrogen Replacement on the Concentrations and Metabolism of Plasma Lipoproteins

Abstract Background. Postmenopausal estrogen-replacement therapy may reduce the risk of cardiovascular disease, and this beneficial effect may be mediated in part by favorable changes in plasma lipid levels. However, the effects on plasma lipoprotein levels of postmenopausal estrogens in the low doses currently used have not been precisely quantified, and the mechanism of these effects is unknown. Methods. We conducted two randomized, double-blind crossover studies in healthy postmenopausal women who had normal lipid values at base line. In study 1, 31 women received placebo and conjugated estrogens at two doses (0.625 mg and 1.25 mg per day), each treatment for three months. In study 2, nine women received placebo, oral micronized estradiol (2 mg per day), and transdermal estradiol (0.1 mg twice a week), each treatment for six weeks. The metabolism of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) was measured by endogenously labeling their protein component, apolipoprotein B. Resu...

Lower prevalence of breast cancer and cancers of the reproductive system among former college athletes compared to non-athletes.

The prevalence (lifetime occurrence) rate of cancers of the reproductive system (uterus, ovary, cervix and vagina) and breast cancer was determined for 5,398 living alumnae, 2,622 of whom were former college athletes and 2,776 non-athletes, from data on medical and reproductive history, athletic training and diet. The former athletes had a significantly lower risk of cancer of the breast and reproductive system than did the non-athletes. The relative risk (RR), non-athletes/athletes, for cancers of the reproductive system was 2.53. 95% confidence limits (CL) (1.17, 5.47). The RR for breast cancer was 1.86, 95% CL (1.00, 3.47). The analysis controlled for potential confounding factors including age, family history of cancer, age of menarche, number of pregnancies, use of oral contraceptives, use of oestrogen in the menopausal period, smoking, and leanness. Of the college athletes, 82.4% had been on pre-college teams compared to 24.9% of the college non-athletes. We conclude that long term athletic training may lower the risk of breast cancer and cancers of the reproductive system.

Statistical methods in evaluating the outcome of infertility therapy

Lack of standardization in analytic methods for assigning infertility data is attributed to inadequate classification of fertility problems, and a lack of consistent methodology in evaluating outcome of infertility therapy. A classification scheme ideally should consider types of fertility problems as well as clinical assessment of its severity. Until an adequate classification system is developed, researchers are encouraged to describe fully the nature of infertility problem examined, and present results for homogenous groups of patients. The life-table method of analysis is a useful technique for assessing infertility statistics. The starting point of this method should depend on the group examined and may be either the date of 1st visit to the clinic or the date that therapy is instituted. Approximate date of conception should be the endpoint. A mathematical model of infertility predicated on the assumption that there is a constant monthly probability of conception of fecundability can be used to derive equations with potential for clinical application.

A randomized, double-blind trial of a gonadotropin releasing-hormone agonist (leuprolide) with or without medroxyprogesterone acetate in the treatment of leiomyomata uteri *

A randomized, double-blind study was performed on 16 women to compare the efficacy of daily subcutaneous (SC) injections of leuprolide acetate (LA; TAP Pharmaceuticals, North Chicago, IL) plus oral placebo tablets (group A, n = 7) with SC LA plus oral medroxyprogesterone acetate (The Upjohn Company, Kalamazoo, MI; group B, n = 9) in the treatment of leiomyomata uteri. Patients in group A had a significant reduction in uterine size from a pretreatment volume of 601 +/- 62 cm3 (mean +/- standard error) to a mean uterine volume of 294 +/- 46 cm3 at 24 weeks of therapy (P less than 0.01). Group B patients had a reduction in uterine volume from 811 +/- 174 cm3 to 688 +/- 154 cm3, which was not statistically significant. However, only one patient in group B experienced hot flashes, whereas six patients in group A had this symptom (P less than 0.01). Both groups demonstrated significant increases in mean hemoglobin concentrations, hematocrits, and serum iron levels at 24 weeks of therapy compared with pretreatment levels.

Characterization of leukocyte subpopulations in the peritoneal fluid of women with endometriosis

Monoclonal antibodies identifying leukocytes subpopulations were applied to smears of laparoscopically collected peritoneal fluid leukocytes and parallel samples of peripheral blood leukocytes from women with endometriosis (n = 33), those with unexplained infertility (n = 9), and fertile controls (n = 8). Peripheral blood leukocyte profiles in all groups were indistinguishable from reported normal values. Peritoneal fluid leukocyte profiles were observed to be different between groups. The most significant elevations in total leukocytes, macrophages, helper T lymphocytes and natural-killer cells were observed in women with stage I and II endometriosis. Significantly elevated levels of total leukocytes, macrophages, and T lymphocytes were also observed in peritoneal fluid from women with unexplained infertility. The results from this study indicate that the peritoneal environment is immunologically dynamic and suggest that cellular immune mechanisms may contribute to reproductive failure in women with endometriosis and unexplained infertility.

Tubal Infertility and the Intrauterine Device

To study the association between intrauterine devices (IUDs) and pelvic inflammatory disease, we compared contraceptive histories in 4185 while women--283 nulliparous women with primary tubal infertility, 69 women with secondary tubal infertility, and 3833 women admitted for delivery at seven collaborating hospitals from 1981 to 1983. The relative risk of tubal infertility associated with IUD use was calculated by means of multivariate logistic regression to control for confounding factors, including region, year of menarche, religion, education, smoking, and reported number of sexual partners. The adjusted risk of primary tubal infertility associated with any IUD use before a first live birth was 2.0 (95 per cent confidence limits, 1.5 to 2.6) relative to nonuse. Users of the Dalkon Shield had an adjusted risk of 3.3 (1.7 to 6.1), users of the Lippes Loop or Saf-T-Coil had a risk of 2.9 (1.7 to 5.2), and users of copper IUDs had a risk of 1.6 (1.1 to 2.4). Women who reported having only one sexual partner had no increased risk of primary tubal infertility associated with IUD use. The adjusted risk of secondary tubal infertility associated with use of a copper IUD after a first live birth was not statistically significant (1.5; 95 per cent confidence limits, 0.8 to 3.0), whereas the risk from similar use of noncopper devices was significant (2.8; 1.3 to 5.9). We conclude that tubal infertility is associated with IUD use, but less so with copper IUDs.

Ovarian failure in long-term survivors of childhood malignancy

The frequency and causes of ovarian failure among 182 long-term survivors of childhood cancer were examined. Twenty-two patients (12%) had ovarian failure. Ovarian failure was found in 17 of 25 patients (68%) who had both ovaries within abdominal radiotherapy fields, in five of 35 patients (14%) whose ovaries were at the edge of the treatment field, and in none of 122 patients with one or both ovaries outside of an abdominal treatment field (p < 10(-4)). The odds for ovarian failure in patients with both ovaries in the field are 19.7 higher than those for other irradiated patients (95% confidence interval, 5.3 to 72.8). Covariate and multivariate analyses of tumor type, age at diagnosis, duration of follow-up, abdominal tumor surgery, abdominal radiotherapy, number of chemotherapeutic agents administered, and cumulative doses of several drugs revealed that the location of the ovaries relative to radiation treatment fields was the only risk factor for subsequent ovarian failure.

A randomized, placebo-controlled, double-blind study evaluating the efficacy of leuprolide acetate depot in the treatment of uterine leiomyomata

Thirty-eight premenopausal women with uterine leiomyomata were enrolled in a randomized, double-blind, placebo-controlled study evaluating the efficacy of depot leuprolide acetate (LA), a gonadotropin-releasing hormone agonist, in decreasing uterine volume. Eighteen women received intramuscular (IM) depot LA 3.75 mg every 4 weeks for 24 weeks (group A); 20 women received IM placebo with the same injection schedule (group B). Group A patients had a mean reduction in pretreatment uterine volume from 505 +/- 93 cu cm (mean +/- standard error of the mean) to 305 +/- 57 cu cm after 12 weeks (P less than 0.05 versus pretreatment) and 307 +/- 57 cu cm after 24 weeks of therapy (P less than 0.05 versus therapy (P less than 0.05 versus pretreatment). At 3 months after cessation of therapy, the mean uterine volume in group A had increased to 446 +/- 92 cu cm (P less than 0.05 versus week 24). Group B patients had no significant change in uterine volume over the 24-week treatment period. These results suggest that depot LA therapy may significantly decrease uterine volume in patients with leiomyomata, but that regrowth of uterine size occurs shortly after cessation of therapy.

Cost-effectiveness of Hormone Replacement Therapy in the Menopause

Costs, risks, and benefits of estrogen-progestin therapy in the menopause were compared with those for estrogen alone, using techniques of cost-effectiveness analysis. With the progestin added, reduced costs of endometrial monitoring and treatment of endometrial lesions more than offset the increased cost of the drug regimen with a net saving of

The North American Menopause Society recommendations for clinical care of midlife women

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