Amnon Brzezinski

Risk factors and prognostic variables in the ovarian hyperstimulation syndrome

This study was undertaken to clarify discriminative roles of multiple epidemiologic, hormonal, and biophysical variables for causation of ovarian hyperstimulation syndrome. Three hundred ninety-six patients with anovulatory infertility had ovulation induction with human menopausal gonadotropin throughout 1822 treatment cycles; 54 cycles (3%) were complicated by ovarian hyperstimulation syndrome. Early follicular serum estradiol and prolactin levels were higher in this group than in controls: 75.5 versus 46.2 pg/ml and 18.5 versus 11.7 ng/ml, respectively (p less than 0.01). On the day of human chorionic gonadotropin administration (day 0) the mean serum estradiol level was 1047 +/- 381 in the group with ovarian hyperstimulation syndrome and 719 +/- 339 pg/ml in controls (p less than 0.0001). In all follicular sizes and in all grades of ovarian hyperstimulation syndrome there was a tendency for more recruited follicles, with significantly more small follicles (12 to 14 mm) present on day 0 in all grades of ovarian hyperstimulation syndrome than in controls. Stepwise logistic regression performed on 22 variables identified a high-risk group for this syndrome; the major features are illustrated by young, lean patients who, after relatively few ampules of human menopausal gonadotropin, develop high estradiol levels and multiple small follicles.

Effect of nutrient intake on premenstrual depression

We examined the occurrence and coincidence of depressed mood and excessive carbohydrate intake in 19 patients who claimed to suffer from severe premenstrual syndrome and in nine control subjects, all as inpatients, during the early follicular and late luteal phases of their menstrual cycles. Mood was assessed with the Hamilton Depression Scale and an addendum that evaluated fatigue, sociability, appetite, and carbohydrate craving. Calorie and nutrient intakes were measured directly. The subjects with premenstrual syndrome significantly increased calorie intake during the late luteal phase (from 1892 +/- 104 to 2395 +/- 93 kcal, mean +/- SEM); carbohydrate intake increased by 24% from meals and by 43% from snacks. Protein intake failed to change, whereas intake of fat, a fixed constituent of all of the test foods, rose in proportion to calorie intake. The Hamilton Depression Scale and addendum scores rose from 2.0 +/- 0.5 to 21.2 +/- 0.8 (Hamilton Scale) and from 0.5 +/- 0.5 to 10.2 +/- 0.6 (addendum) among subjects with premenstrual syndrome during the luteal phase but failed to change among the controls (2.1 +/- 0.8 to 2.4 +/- 0.8, and 0.4 +/- 0.3 to 0.6 +/- 0.3). Consumption of a carbohydrate-rich, protein-poor evening test meal during the late luteal phase of the menstrual cycle improved depression, tension, anger, confusion, sadness, fatigue, alertness, and calmness scores (p less than 0.01) among patients with premenstrual syndrome. No effect of the meal was observed during the follicular phase or among the control subjects during either phase. Because synthesis of brain serotonin, which is known to be involved in mood and appetite, increases after carbohydrate intake, premenstrual syndrome subjects may overconsume carbohydrates in an attempt to improve their dysphoric mood state.

Effects of hormone replacement therapy on weight, body composition, fat distribution, and food intake in early postmenopausal women: a prospective study.

OBJECTIVE To evaluate the effects of hormone replacement therapy (HRT) on body weight and composition, fat distribution, and food intake in women entering the climacteric. DESIGN Prospective clinical study. SETTING Outpatient menopause clinic at a tertiary medical center. PARTICIPANTS Sixty-three early postmenopausal women (44 to 54 years old) were prospectively studied for 1 year. They consisted of two groups: group A, 34 subjects who initiated continuous estrogen and progestin treatment (daily oral conjugated estrogen 0.625 mg and medroxyprogesterone acetate 2.5 mg), and group B, 29 women who refused hormonal therapy and served as controls. The age, menopausal status, initial anthropometric measurements (weight, body mass index [BMI], fat mass, and waist-to-hip girth ratio), and daily food intake (total caloric intake and food composition) were similar in both groups. INTERVENTIONS Anthropometric measurements were performed before commencement of HRT use and after 12 months. MAIN OUTCOME MEASURES Anthropometric measurements included BMI, waist-to-hip girth ratio, and body composition (the percentage of body fat and water) estimated by means of infrared interactance. Daily food intake was also recorded. RESULTS The body weight and fat mass increased significantly in both the treatment (73.22 +/- 2.01 [mean +/- SE] to 75.57 +/- 1.12 kg) and the control group (71.45 +/- 3.11 to 73.51 +/- 1.23 kg). However, a significant shift from gynoid to android fat distribution was observed only in the control group (waist-to-hip ratio shifted from 0.80 +/- 0.01 to 0.85 +/- 0.01), whereas no significant change was observed in the treatment group (0.81 +/- 0.01 to 0.82 +/- 0.01). Caloric and macronutrient intake did not change in either group. CONCLUSIONS These results indicate that continuous daily estrogen and progestin replacement therapy neither prevents nor increases early postmenopausal weight gain and fat accumulation. However, it does minimize the shift from gynoid to android fat distribution.

Ritualistic female genital mutilation: current status and future outlook.

Ritualistic sexual mutilation of females dates back to the fifth century B.C. This traditional practice is a social as well as a health issue that affects the physical and mental well being of the women who undergo it. Although practiced mostly in African countries north of the equator and the Middle-East, concern has recently been expressed that female genital mutilation is also being practiced in the U.S., Europe, and other western countries by immigrants from these countries. This review describes the various types of female genital mutilation and presents the historical and cultural background of the tradition, outlines the medical, psychological and sexual problems, and discusses the current status and future outlook for this tradition, emphasizing social, medical, and legislative aspects.

Gradual discontinuation of hormone therapy does not prevent the reappearance of climacteric symptoms: a randomized prospective study.

kappaB activity and nitric oxide production in rejecting cardiac allografts. Transplantation 1998; 66: 838. 28. Boyd JH, Mathur S, Wang Y, et al. Toll-like receptor stimulation in cardiomyoctes decreases contractility and initiates an NF-kappaB dependent inflammatory response. Cardiovasc Res 2006; 72: 384. 29. Andrade CF, Kaneda H, Der S, et al. Toll-like receptor and cytokine gene expression in the early phase of human lung transplantation. J Heart Lung Transplant 2006; 25: 1317. 30. Krieger NR, Yin DP, Fathman CG. CD4 but not CD8 cells are essential for allorejection. J Exp Med 1996; 184: 2013. 31. Phillips NE, Markees TG, Mordes JP, et al. Blockade of CD40-mediated signaling is sufficient for inducing islet but not skin transplantation tolerance. J Immunol 2003; 170: 3015. 32. Smiley ST, Csizmadia V, Gao W, et al. Differential effects of cyclosporine A, methylprednisolone, mycophenolate, and rapamycin on CD154 induction and requirement for NFkappaB: Implications for tolerance induction. Transplantation 2000; 70: 415.

Periurethral Injection for the Treatment of Urinary Incontinence

Periurethral injection of substrates that compress, support, or narrow the bladder neck for the treatment of stress incontinence is not new. Several injectable compounds have been used in a small number of patients during the 1940s and through the 1960s; however, the results were not very successful and often led to significant complications. More recently, two major materials have been developed that seem to be useful in treating stress incontinence by periurethral injection: Polytef paste and GAX collagen. Other injectables include autologous fat tissue and silicone microimplants. The most suitable patients for periurethral injection are elderly women, patients who constitute high operative risk, and those with stress incontinence due to intrinsic sphincter failure. Patients with stress incontinence due to a combination of urethral hypermobility and intrinsic sphincter deficiency with failure of suspension procedure may also benefit from the procedure. The reported long-term (more than 24 months) success rates according to the various substances are as follows: Teflon (Polytef) (E.I.du Pont de Nemours and Co, Wilmington, DE): 30 to 38 percent cured or improved; repeated injections usually do not improve the outcome; mostly minor complications with case reports of more serious side effects such as periurethral granuloma formation and bladder outlet obstruction. GAX collagen: 69 to 77 percent subjectively cured or improved after 24 months; 54 to 57 percent objectively cured or improved, the reported morbidity in these procedures is minimal; repeated injections can improve the outcome. The experience with autologous fat and silicone microimplants is insufficient, with an overall success rate of 70 percent (1-40 months follow-up; mean 12 months) and 58 to 70 percent (17-36 months), respectively. Most of the procedures are performed as outpatient cases, and some under local anesthesia. These procedures are minimally invasive, usually safe and well tolerated, require shorter hospitalization, and are cost effective. In conclusion, in carefully selected patients, periurethral injection seems to be a reasonable option in the modern treatment of female stress incontinence.

The pineal gland - Its possible roles in human reproduction

The paper discusses the role of the pineal gland in controlling mammalian reproduction, with particular attention given to the role of melatonin in polyestrus mammals, like humans and laboratory rodents. Evidence is cited indicating the influence of melatonin production and blood content on the age of puberty, the timing of the ovulatory cycle, gonadal steriodogenesis, and patterns of reproductive behavior. It is suggested that abnormal patterns of melatonin might be associated with amenorrhea, anovulation, unexplained infertility, premature menopause, and habitual abortions.

The effect of hormone therapy on the risk for age-related maculopathy in postmenopausal women.

Objective To evaluate the effect of postmenopausal hormone therapy (HT) as well as the use of oral contraceptives and lifetime endogenous hormone exposure on the risk for age-related maculopathy (ARM) in postmenopausal women. Design This was a cross-sectional, controlled study. A total of 102 women from 60 to 80 years of age who were receiving HT and 100 controls underwent a detailed clinical funduscopic evaluation and stereoscopic fundus photography for the presence and grading of ARM. All participants completed a standardized questionnaire regarding vascular risk factors, HT, and lifetime exogenous and endogenous estrogen and progesterone exposure. Statistical analysis was performed using Students t test, &khgr;2 test, and a multivariate logistic regression model. Results The HT and the non-HT groups did not differ in terms of early (11% v 15%), late (6% v 6%), or wet (2% v 2%) ARM prevalence rates. Women with ARM were significantly older than controls (69 v 66 years; P = 0.001, 95% CI = 0.008 − 0.027) and were more likely to have ischemic heart disease (21% v 9%; OR = 2.86, P = 0.03, 95% CI = 0.020 – 0.360). Lifetime exogenous and endogenous hormone exposures and other cardiovascular risk factors were not significantly different among women with ARM as compared with controls. Conclusion Postmenopausal HT may not affect the risk for either early or late ARM in women aged 60 to 80 years. The risk for both entities is not necessarily affected by either exogenous or endogenous lifetime hormone exposure. A history of ischemic heart disease may be associated with an increased risk for ARM.

Does postmenopausal hormone replacement therapy affect intraocular pressure

Purpose:To assess the effects of postmenopausal hormone replacement therapy (HRT) on intraocular pressure (IOP). Patients and Methods:This was a cross-sectional controlled study, including 107 women aged 60 to 80 years receiving HRT and 107 controls who have never received HRT. All subjects underwent IOP assessment and funduscopic photography for cup-to-disc (C/D) ratios, and completed questionnaires regarding personal and family history of glaucoma, hormone replacement therapy, lifetime estrogen and progesterone exposure, and cardiovascular risk factors. Main Outcome Measures included IOP, prevalence of increased IOP, and C/D ratios. Results:The groups did not differ in mean IOP (15.3 versus 15.3 mm Hg), mean vertical (0.18 versus 0.21) and horizontal (0.17 versus 0.14) C/D ratios, and in prevalence of increased IOP (15% versus 14%), C/D ratio (7% versus 7%), or glaucoma (9% versus 11%). A personal history of ischemic heart disease was the only risk factor associated with increased IOP (O.R. = 4.63, P = 0.003). Lifetime estrogen and progesterone exposure, including pregnancies, deliveries, menstruation years, and the use of oral contraceptives did not significantly affect the risk for increased IOP. Conclusion:Hormone replacement therapy and lifetime estrogen and progesterone exposure do not seem to affect IOP or the risk for increased IOP. A personal history of ischemic heart disease may be associated with a higher risk for this disorder.

???Melatonin Replacement Therapy??? for Postmenopausal Women: Is It Justified?

ObjectiveAging, sleep, and breast cancer are important concerns of postmenopausal women. There now is evidence that melatonin, the hormone secreted by the pineal gland, may have a role in the regulation of various human biological processes including sleep, tumor growth, and perhaps aging. The current knowledge concerning these questions is briefly and critically reviewed. Conclusions Melatonin might be implicated in menopause-associated processes such as insomnia, breast cancer, and general aging. Its beneficial effect on sleep has been demonstrated in controlled clinical trials, however, “melatonin replacement therapy” for all postmenopausal women is currently unjustified.