Showing papers in "International journal of fertility and women's medicine in 2001"

Circadian rhythm chaos: a new breast cancer marker.

Abstract: The most disappointing aspect of breast cancer treatment as a public health issue has been the failure of screening to improve mortality figures. Since treatment of late-stage cancer has indeed advanced, mortality can only be decreased by improving the rate of early diagnosis. From the mid-1950s to the mid-1970s, it was expected that thermography would hold the key to breast cancer detection, as surface temperature increases overlying malignant tumors had been demonstrated by thermographic imaging. Unfortunately, detection of the 1-3 degrees C thermal differences failed to bear out its promise in early identification of cancer. In the intervening two-and-a-half decades, three new factors have emerged: it is now apparent that breast cancer has a lengthy genesis; a long-established tumor-even one of a certain minimum size-induces increased arterial/capillary vascularity in its vicinity; and thermal variations that characterize tissue metabolism are circadian ("about 24 hours") in periodicity. This paper reviews the evidence for a connection between disturbances of circadian rhythms and breast cancer. Furthermore, a scheme is proposed in which circadian rhythm "chaos" is taken as a signal of high risk for breast cancer even in the absence of mammographic evidence of neoplasm or a palpable tumor. Recent studies along this line suggest that an abnormal thermal sign, in the light of our present knowledge of breast cancer, is ten times as important an indication as is family history data.

Studies on the significance of positive bacterial semen cultures in male fertility in Nigeria

Abstract: Early warning signals (EWS) of altered reproductive potential may be very important in the prevention and management of male infertility. The presence of bacteria in semen (bacterisemia) may be an EWS. This was evaluated by determining the incidence of bacteria in semen of males with fertility problems in Benin City by culturing their semen. Diluted semen samples were cultured on blood agar chocolate agar MacConkey agar nutrient agar and sabouraud dextrose agar slants for the isolation of microorganisms. Colonies of a single type of microorganism (>1000 cfu/ml) were picked for identification and sensitivity tests using antibacterial agents. Each semen sample was further processed for spermatozoal morphology and motility presence of peroxidase-positive cells and other accompanying cells. Correlative studies on the relationship between bacterisemia and semen/spermatozoa variables such as total number and motility were also done. Pathogenic microorganisms were present in 78/163 (47.1%) semen samples. The microbial isolates were Staphylococcus aureus 35 (43.7%) Klebsiella species 22 (28.2%) Escherichia coli 9 (11.5%) and Candida albicans 6 (7.7%). The bacterial isolates were most sensitive to ceftazidime and pefloxacin and least to amoxycillin and tetracycline. There was a positive correlation (r = 0.9774) between azoospermia in males and presence of Candida albicans in semen as well as between the presence of microorganisms and poor semen quality (r = 0.8563) and the presence of microorganisms and reduced motility (r = 0.8246). Presence of pathogenic microorganisms in semen which may be related to a breach in the integrity of the blood-testes barrier may provide early warning signals of impairment of male fertility. (authors)

Cervical dysplasia in pregnancy: progression versus regression post-partum.

Abstract: OBJECTIVE To assess the natural history of cervical dysplasia during pregnancy and determine the rates for progression or regression post-partum by the severity of the lesion. METHOD This was a retrospective study of 100 patients screened by PAP smear. Lesions were graded by colposcopy and biopsy, and followed post-partum. RESULTS Lesions were graded as ASCUS, LGSIL, and HGSIL. The majority of lesions showed a tendency to regress post-partum (approximately 64%), a trend that was statistically significant (P < .003). A substantial minority (approximately 34%) showed no change in severity of the lesion. The tendency for lesions to progress in severity was very low (approximately 3%). No patient had microinvasive disease. Of patients who had CIS, persistence of this lesion post-partum was present in 67%. CONCLUSION Patients with cervical dysplasia in pregnancy may be followed conservatively with colposcopy and biopsy.

Dyslipidemia with particular regard to apolipoprotein profile in association with polycystic ovary syndrome: a study among Indian women.

Abstract: OBJECTIVE To investigate putative dyslipidemia in women with polycystic ovary syndrome (PCOS) with particular emphasis on specific parameters of atherosclerotic risk, and to assess the independent influence of obesity and hyperandrogenemia on these parameters. SUBJECTS Women investigated were among those attending the infertility clinics. Three groups of women were studied: (I) a core study group consisting of oligomenorrhoeic, chronically anovulatory women with or without obesity in whom polycystic ovaries were confirmed through ultrasound evidence, and were established to be the cause of infertility; II) a control group of non-hirsute, non-obese women with regular menstrual cycles; and (III) a group of controls consisting of women with obesity, but with normal ovarian morphology and regular menstrual cycles. METHODS All three study groups were investigated for androgen (total testosterone) and lipid-lipoprotein profile, including apolipoproteins, ApoA1 and ApoB. Retrospective analysis of the data was carried out to assess hyperandrogenism in the study group of women with PCOS as well as to investigate changes in the lipid-lipoprotein profile, particularly the measures of cardiovascular risk, ApoA1 and ApoB. RESULTS Triglycerides showed a significant increase in the PCOS group compared to controls, whereas HDL-cholesterol as well as HDL-carrying ApoA1 showed a significant decrease (P < .05). Also a significant finding was the decrease in ApoA1/ApoB ratio among the women with PCOS compared to both controls and obese women. A direct negative correlation of this decrease in ApoA1/ApoB ratio with the Body Mass Index was also confirmed in the study. Hyperandrogenemia in terms of significantly raised total testosterone levels was found in 30% of the PCOS women. However, no direct correlation of this increase with changes in lipid-lipoprotein profile could be observed. CONCLUSION The study confirms the trend toward dyslipidemia among women with PCOS, particularly in parameters associated with cardiovascular risk. A significant association of obesity rather than raised testosterone with this dyslipidemia was also confirmed by the study.

Comparative cardiovascular effects of different progestins in menopause.

Abstract: Progesterone receptors are present in the arterial wall and it is, therefore, likely that the arterial effects of progestins are mediated through progesterone receptors as well as through down-regulation of the estradiol receptor. Progestin therapy affects arterial function, as it can stabilize arteries in a state of vasomotor instability, but may also induce vasoconstriction of estrogenized vessels. Thus, the cardiovascular effects of progestins may influence the cardioprotective effect of estrogens. There has been some concern that a combined estrogen-progestogen therapy may attenuate some of estrogen's beneficial effects on cardiovascular health. This is a reflection of the past epidemiologic studies which have used primarily unopposed estrogen. The PEPI trial is the only large-scale, long-term study to compare directly the effects of different combined hormone replacement therapy regimens upon plasma lipids in healthy women. This study has shown that the adjunctive clinical impact of different progestogens on the beneficial effect of estrogen replacement therapy is trivial. It has never been proved that in normocholesterolemic women, e.g., those included in the PEPI trial, the increase in HDL reduces cardiovascular mortality or morbidity. Based on the results of PEPI, hormone replacement therapy has positive effects on key heart disease risk factors and endometrial tissue, and the magnitude of those effects does not differ significantly across the hormone replacement therapy regimens used. At present there are only few and inconclusive data available on the vascular effect of progestins in menopausal women. Some studies found that progestins reduced the beneficial effect of estrogens, while others did not. Our group has recently shown that different estrogen-progestin treatments have different effects upon vascular reactivity and that a careful selection of the progestin to be added to estrogen is of capital importance to preserve, or even enhance the positive vascular effects of estrogens. Few epidemiological studies have investigated the effect of adding a progestin to estrogen therapy upon cardiovascular mortality and morbidity, and all have suggested that hormone replacement therapy may be more effective than estrogen replacement alone in reducing cardiovascular events in primary prevention. The results of the recently published Heart and Estrogen/progestin Replacement Study (HERS) have added some critical data on the effect of hormone replacement therapy for secondary prevention in women with coronary artery disease. The study, however, is affected by several important methodological and statistical problems, which make its interpretation difficult and its conclusions useless for clinical practice. The results of the study should be evaluated with caution by physicians who give advice on hormone replacement therapy, and no woman should be taken off hormone replacement therapy because of HERS. Of importance, the results of HERS should not be used to suggest alternative forms of treatment, especially the selective estrogen receptor modulators (SERMs), for cardiovascular protection in postmenopausal women.

Beyond HERS: some (not so) random thoughts on randomized clinical trials.

Abstract: Science is the process of discovering truth, and "truth" is sampled each time we do a study. The results from all of our studies will be distributed around the truth, and different study designs give different amounts and different qualities of sampled material. Truth is ascertained only when sufficient numbers of appropriate studies are conducted, and no one study or one study design has a monopoly on truth. Currently, the randomized clinical trial is considered the penultimate study design and the ultimate test of the hypothesis, but only if it is double-blinded, placebo-controlled, and analyzed by an intention-to-treat protocol. The study design most similar to the randomized controlled trial is the prospective cohort study. In this observational approach, a cohort (group of individuals) is assembled and followed in real time while end points (e.g. breast cancers, heart attacks, fractures) accrue. This is contrasted to the randomized controlled trial, where a group of individuals is assembled, intervened upon, and followed in real time while end points accrue. The major advantage of the randomized controlled trial over an observational study is that the randomization process should eliminate any "bias" in the exposure of interest. However, the randomized controlled trial, like all study designs, has other limitations. Major limitations of the randomized controlled trial include significant financial and other costs, problems with external generalizability, the placebo effect, external monitoring, multi-center differences, and the (frequently problematic) intention-to-treat analysis rule. Many of these limitations do not occur in prospective cohort studies. For example, since a placebo is not administered in an observational study, there is no placebo effect, and since the study is not monitored by a data and safety monitoring board, abrupt truncation of the study duration is not usually seen in observational cohort studies. These limitations of randomized controlled trials are discussed, with specific references to several recently published randomized controlled trials in women (HERS, NSABP P-1, and the Royal Marsden Hospital trials). The HERS trial is significant because despite overwhelming observational evidence that menopausal estrogen therapy prevents heart disease, HERS found no overall difference in heart disease events in women assigned to an estrogen-plus-progestin intervention. The NSABP P-1 and the Royal Marsden Hospital trials are significant in that they were testing the same hypothesis (whether tamoxifen can prevent breast cancer), but came to entirely different conclusions. Two major questions will be posed from this specific review: One: Given conflicting evidence by study design (observational vs. randomized clinical trial), does menopausal estrogen therapy protect against heart disease? Two: Given conflicting evidence within study design (conflicting randomized clinical trials), does tamoxifen prevent breast cancer?

Intermittent versus continuous sertraline therapy in the treatment of premenstrual dysphoric disorders.

Abstract: Objective Premenstrual dysphoric disorder (PMDD) is a combination of mood disturbances and physical symptoms that reduce the quality of individual life and the functionality of the individual. Many women do not consider the complaints arising in the luteal phase of the menstrual cycle as a psychiatric disorder and, thus, do not seek treatment. Those who take their complaints to doctors usually apply to gynecology clinics. The aim of the present study is to analyze the psychiatric disorders observed in patients with PMDD and to compare the continuous and intermittent administration of sertraline. Materials and methods PMDD was investigated in the patients admitted to the Gynecology Clinic of the Medical School of Fatih University. The patients were asked to fill out forms designed in accordance with PMDD diagnosis criteria as defined in DSM IV. Results Among the 267 patients who filled out the forms, 162 (60.7%) were PMDD positive. Of the PMDD-positive patients, 133 accepted a psychiatric interview; 36 (27%) of them had depression, obsessive-compulsive disorder, anxiety and somatoform disorders as an accompanying disorder. Out of 162 PMDD-positive patients 94 accepted medical treatment; 71 patients were given sertraline on a continuous basis, and 23 patients took sertraline intermittently in the luteal phase of the cycle. Because of side effects, 44 (62%) of the continuous therapy and 22 (96%) of the intermittent therapy group stopped medication. At the end of 6-month follow-up, continuous use of sertraline was found to be significantly more tolerated than intermittent therapy in the treatment of PMDD (chi2 = 7.88, p = 0.005). Conclusion In patients with the symptoms of PMDD, psychiatric evaluation should be encouraged by gynecology clinics, and continuous administration of sertraline should be the choice because of patients' greater acceptance of the therapy.

Corticosteroid-induced osteoporosis.

Abstract: Since Harvey Cushing first noted the coexistence of excess cortisol and loss of skeletal mass over 50 years ago, it has been accepted that supraphysiologic doses of corticosteroids cause clinically significant bone loss. Currently, high-dose oral corticosteroids are used to treat people with a variety of medical conditions, including: rheumatic diseases, such as rheumatoid arthritis, polymyalgia rheumatica, systemic lupus erythematosus and vasculitis; inflammatory lung diseases, like asthma; gastrointestinal diseases, such as inflammatory bowel disease and chronic liver disease; skin diseases, in particular pemphigus, and more recently those who have undergone transplantation. Clinically significant bone loss occurs in the vast majority of patients exposed to corticosteroids, and fractures at the spine and hip have been reported with corticosteroid use. Between 30 and 50 percent of patients taking long-term corticosteroids will experience fractures. Today, fractures due to corticosteroid-induced osteoporosis may be prevented. A number of well-designed randomized controlled trials have been conducted that demonstrate preservation and, in some instances, actual increases in bone mass with the use of appropriate drug treatment. Some have even demonstrated reductions in fracture risk. As a result, it is extremely important for clinicians to appreciate the very high risk for vertebral fracture, particularly in postmenopausal women on corticosteroids.

Beta 2-glycoprotein I is a good indicator of certain adverse pregnancy conditions.

Abstract: Objective To compare levels of beta2-glycoprotein I antibodies with six different antiphospholipid antibodies (aPL) in sera from patients with certain adverse pregnancy conditions. Patients and methods aPL levels were examined in pregnant women with anti-phospholipid syndrome (26), pre-eclampsia (32), autoimmune disease (12), or diabetes mellitus (23) and in a group with physiological pregnancy (38). A commercial ELISA was used to determine the serum levels of anti-beta2-GPI (Immunotech) in isotypes IgG and IgA, and anti-cardiolipin levels (Milenia) in IgG and IgM. aPL screening also included L-alpha-phosphatidic acid, L-alpha-phosphatidylethanolamine, L-alpha-phosphatidyl-DL-glycerol, L-alpha-phosphatidylinositol, and L-alpha-phosphatidyl-serine (Sigma, U.S.A.) in IgG and IgM. Statistical analysis of all aPL levels was made by cut-off levels for Ig isotypes by using 3 SD or 95th percentile calculated using STATGRAPHICS. Results Positive levels of antibodies against beta2-GPI in IgA are more frequently associated with a diagnosis of anti-phospholipid syndrome, pre-eclampsia, and autoimmune disease in pregnant women than with diabetes mellitus in pregnancy. Very high interindividual differences in aPLs (against inositol, L-serine, cardiolipin, and beta2-glycoprotein in IgG and IgA) were found in serum from women with pregnancy complicated by anti-phospholipid syndrome, pre-eclampsia, and autoimmune disease. Pregnant patients with diabetes mellitus had higher serum levels in aPLs to DL-glycerol, inositol, L-serine, and beta2-glycoprotein. Positive aPL levels predominate in isotype IgG. Very low levels of aPLs to phosphatidic acid and phosphatidyl-ethanolamine were detected in all groups studied. Conclusion Serum levels of anti-beta2-GPI could serve as a better prognostic marker in complicated pregnancy than the panel of seven different anti-phospholipid antibodies. Detection of anti-beta2-GPI is proposed as a first step of the screening for aPLs.

Serum creatine kinase is not a reliable indicator of ectopic pregnancy.

Abstract: OBJECTIVE It has been reported that elevation in creatine kinase may be used as an indicator of ectopic pregnancy as a consequence of trophoblast invasion of the smooth muscle layer of the Fallopian tube. In this study, we attempt to verify this observation and establish the sensitivity and positive predictive value of the test. METHODS Serum creatine kinase (MM-fraction) was obtained from patients presenting with possible ectopic pregnancy prior to surgical intervention. Ectopic pregnancies were confirmed by laparoscopy. Noted was whether the gestation was ruptured or unruptured, its location in the tube, and estimated cross-sectional tubal distention. Controls consisted of patients with first-trimester pregnancies simulating ectopic pregnancy, i.e., patients having a positive pregnancy test, complicated by vaginal bleeding and/or abdominal pain. RESULTS The distribution of creatine kinase values for both patients with ectopics versus control are positively skewed, with a mode of 10-19 U/L. The mean creatine kinase for ectopic pregnancies was 62.3 U/L, S.D. = 63.1 U/L. For controls, the mean creatine kinase = 40.8 U/L, S.D. = 30.1 U/L. The difference in these means is significant (p = 0.04), but weakly so. In addition, for ectopic gestations there was no significant difference in creatine kinase values with regard to degree of tubal distention, gestation location, or whether rupture had occurred, thereby limiting the clinical value of this test. CONCLUSIONS Although the mean value of serum creatine kinase is statistically significantly higher in ectopic pregnancy relative to controls, the distribution curve for creatine kinase values for ectopics is broad, with much overlap with the control curve. Hence, the sensitivity and positive predictive value for this test is poor.

HRT dosing regimens: continuous versus cyclic-pros and cons.

Abstract: The introduction of new products, lower dosages, and better continuous and cyclic regimens allows for individualized treatment aimed at minimizing risk and side effects, while maximizing confidence and compliance. Since the major side effect of HRT that discourages long-term use is vaginal bleeding, newer regimens are designed to minimize it. The lowest doses of estrogen currently approved by the FDA for prevention of osteoporosis include 0.3 mg esterified estrogens, 0.025 microg transdermal estradiol patch, and 0.5 mg micronized estradiol. In most naturally menopausal women or those over 65 years of age, conjugated estrogen 0.3 mg (with adequate calcium intake) is protective against bone loss and cardiovascular disease. These low doses are often used with cyclic progestins every 3 to 4 months. Advantages of cyclic therapy using low-dose estrogen include minimal progestin exposure, low rate of withdrawal bleeding, lowered side effects, and, often, higher comfort level. Cyclic estrogen regimens with higher doses have been in use longer, but they often necessitate more frequent progestin treatment and may result in cyclic bleeding or breast tenderness. While HDL- and LDL-cholesterol changes are greater and more beneficial during higher-dose oral cyclic therapy, the large increase in triglycerides is of concern. The most commonly used continuous combined regimens include conjugated estrogen plus daily progestin orally or the combination estradiol/norethindrone acetate transdermal patch. Continuous combined regimens are simple and easy-to-use, and are designed to minimize bleeding. Multiple studies suggest that the mechanism of benefit provided by estrogen goes beyond estrogen's favorable impact on lipoproteins, which is blunted by daily use of synthetic progestins.

Endometriosis: traditional perspectives, current evidence and future possibilities.

Abstract: Endometriosis is a disease that is wide-ranging in location and highly varied in clinical presentation, and of probably complex etiology. Since convincing studies on this condition are few, many physicians maintain a traditional perspective in management and treatment. There is new evidence, though, on some aspects of endometriosis. Therefore, this review of many of the better studies outlines treatments that are aimed at pain and/or infertility, plus an assessment of the outcomes obtained. The methods covered are symptomatic treatment; ovarian suppression; surgery; combined ovarian suppression and surgery; ovarian hyperstimulation; assisted reproductive technology; and comprehensive management, including counseling.

A minimally invasive vasectomy with the no suture, inline method for vas occlusion.

Abstract: Objective-The current vasectomy methods including the no scalpel vasectomy (NSV) have received considerable attention in recent years because they are minimally invasive and utilize special instruments to expose the vas. However at least 28 different methods for vas occlusion have been utilized with these procedures and some postoperative complications have been attributed to the method of vas occlusion. Therefore in this report we will critique the existing methods for vas occlusion and introduce a new and rapid method. Patients and Methods-The NSV instruments were used to expose the vas but in addition a fine skin hook a short-bladed tenotomy scissors and a hand-held hotwire cautery were used for the new no suture inline method of vas occlusion. No ligatures were placed around the vas no portion of the vas was removed and the mesentery behind the vas was not disturbed. The vas sheath was disrupted there was luminal cautery on both the abdominal and testicular sides a section of vas was detubularized and trimmed and its epithelium was destroyed by cautery. This technique has been performed in 158 consecutive cases. Results-All patients have demonstrated complete azoospermia on two follow-up semen analyses with no pregnancies reported. Conclusion-This new method of vas occlusion seems to be rapid and compatible with the NSV instruments. (authors)

New aspects of injectable contraception.

Abstract: Despite the availability of efficacious and safe contraceptive agents, not all women's contraceptive needs are being met. An injectable contraceptive method offers convenience and encourages compliance, both very important aspects for women seeking ideal contraception. Depot medroxyprogesterone acetate (DMPA) is a long-acting injectable, and is highly effective; one injection provides 3 months of contraception. Drawbacks of DMPA include irregular bleeding and a slow return to fertility. A new monthly injectable contraceptive agent is medroxyprogesterone acetate/estradiol cypionate suspension (Lunelle). It provides menstrual regulation and a rapid return to fertility. The estrogen ensures a withdrawal bleed monthly; however, women with contraindications to estrogen-containing contraception are not candidates for Lunelle.

Changes in symptoms, lipid and hormone levels after the administration of a cream with phytoestrogens in the Climacteric--preliminary report.

Abstract: OBJECTIVE To establish the changes in lipid and hormone levels, as well as in symptoms, after topical application of a cream with phytoestrogens in postmenopausal women. METHODS 30 postmenopausal women were studied. At baseline and 1 month after the beginning of treatment, levels of FSH, estradiol, estrone, testosterone, androstenedione, dehydroepiandrosterone, total cholesterol, HDL-C, LDL-C, and triglycerides were measured. Climacteric symptoms were evaluated with a modified Kupperman's index (KI). The subjects received a cream with phytoestrogens (n = 15) or placebo (cold cream) (n = 15) in a randomized, double-blind manner. Statistically significant differences were determined by Student's t test. RESULTS No differences were found in hormones, lipids, or in KI between the groups. When comparing each group separately, only a significant decrease in KI was found, in both groups, at the end of the treatment. CONCLUSIONS This cream with phytoestrogens had an effect only in climacteric symptoms, but similar to the placebo. The lack of effect in the other variables was probably due to the administration route, or to a lack of effect of this product.

Effects of two oral contraceptives, containing 30 or 20 microg of ethinyl estradiol in combination with gestodene, on blood coagulation and fibrinolysis in Brazilian women.

Abstract: Blood coagulation and fibrinolytic variables were evaluated in 46 Brazilian women treated with either of two monophasic oral contraceptives (OCs) containing 30 or 20 mcg of ethinyl estradiol and 75 mcg of gestodene. The effects on procoagulants anticoagulants pro-fibrinolytics and antifibrinolytics and fibrin turnover were evaluated after treatment for six consecutive cycles the impact of reduction of ethinyl estradiol dosage on these effects being assessed. The OC containing 30 mcg of ethinyl estradiol significantly increased the activities of factors VIII and X whereas the one containing 20 mcg of ethinyl estradiol caused no changes in clotting factors. Neither treatment altered fibrinogen levels or factor VII IX or XII activity. There were no changes in antithrombin levels but treatment with 30 mcg ethinyl estradiol increased protein C levels and treatment with 20 mcg decreased total protein S levels. Concerning the fibrinolytic parameters both OCs increased plasminogen activity whereas no changes in plasminogen activator inhibitor-1 tissue plasminogen activator alpha-2-antiplasmin or fibrin degradation products were observed. The reduction in ethinyl estradiol dosage from 30 to 20 mcg eliminated the effects on factors VIII and X. The results show that the OC studied did not cause sufficient changes to indicate that there may be a correlation between these laboratory alterations and clinical results. The lack of reports concerning the hemostatic effects of OCs on Brazilian women hinders comparison of the present data with those obtained for other ethnic groups at different geographical locations and emphasizes the importance of such a study for future epidemiological investigation of the prothrombotic effects of OCs in Brazilian women. (authors)

The diagnosis and treatment of male infertility in the new millennium.

Abstract: Treatment of male infertility accomplished far-reaching advances in the past decade. Semen analysis has given rise to sperm function tests. Microsurgery, e.g., reversal of vasectomy, has reached new heights in sperm retrieval directly from the testis/epididymis and in intracytoplasmic sperm injection (ICSI). Furthermore, genetic testing-for an ever-widening range of anomalies-is the norm in modern clinical practice. This review of what is possible, and now even common, in male infertility treatment focuses on sperm function, and then deficits/anomalies and their treatment; and testicular function and dysfunction, with descriptions of hormonal and surgical techniques that now offer fatherhood to men with types of infertility that strongly imply the need for genetic counseling.

Estrogens and hormone replacement therapy: is there a role in the preservation of cognitive function?

Abstract: Alzheimer's disease affects as many as 40% of Americans over the age of 80 and, as such, is a major public health issue. Interestingly, there is a two- to threefold greater prevalence in women than in men. It has been estimated that the prevalence of Alzheimer's disease will quadruple over the next half century. There have been implications of an effect of estrogen on neurological function for many years. As long as 50 years ago a study published in the gerontology literature suggested that the administration of i.m. estrogen in a nursing home population was associated with improvement in memory and a delay in progression of memory loss. Most recently there has been great interest in the effect of estrogen on both neurons and the CNS vasculature. A study evaluating verbal memory and abstract reasoning in over 700 women without dementia demonstrated that women who had used estrogen for as little as 1 year had significant improvements in baseline cognitive testing. The pathogenesis of Alzheimer's disease and neurodementia is better understood today but remains incompletely elucidated. It has been suggested that inflammation exists both within the neurovasculature and the stroma and that beta-amyloid creates an inflammatory reaction. In Alzheimer's patients there are abnormal deposits of proteins such as beta-amyloid, presenelin, and apolipoprotein E-4. Estrogen may act as a protectant against these inflammatory mediating proteins. While a recent trial demonstrated no impact of estrogen in patients diagnosed with mild to moderate Alzheimer's, other studies have suggested that estrogen use significantly delays disease onset. One study followed over 1,100 subjects who were free of disease at trial initiation over a period of 1 to 5 years. Even short-term use of estrogen imparted protection, although longer-term estrogen use was associated with greater protection. Unfortunately, most women are unaware of the potential beneficial effect of estrogen on cognitive function. Prospective studies are under way to try to delineate how estrogen impacts Alzheimer's disease.

Hypothalamic-pituitary-thyroidal axis dysfunction and cortisol secretion in patients with nonclassical congenital adrenal hyperplasia.

Abstract: Objective-The purpose of this study was to evaluate thyroid function and TSH and cortisol (F) secretion in hyperandrogenemic women with nonclassical congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency (Group A) when compared with women with hyperandrogenemic symptoms (menstrual irregularities, hirsutism, acne, seborrhea and sterility) of other etiologies (Group B). Methods-Seventy-two women were subjected to stimulation of the adrenal cortex with i.v. ACTH administration in the early proliferative phase of the menstrual cycle. Basal plasma TSH, T 3 , T 4 , and FTI as well as basal and ACTH-stimulated plasma F and 17-hydroxyprogesterone levels were determined. Results-According to internationally accepted criteria and HLA haplotyping, we diagnosed 28 NC-CAH patients as well as affected heterozygotes of the disease. No significant difference was found in the plasma T 3 , T 4 , or FTI or F concentrations between the women of the two groups. On the contrary, plasma TSH levels were significantly lower in patients with 21-hydroxylase deficiency when compared to the women with hyperandrogenemic symptoms of other etiologies. Conclusion-The results of this study support a dysfunction of the hypothalamic-pituitary-thyroidal axis due to altered ACTH secretion patterns.

STD update: screening and therapeutic options.

Abstract: Sexually transmitted diseases (STDs) are some of the most common causes of illness worldwide. Prevention and educational programs have helped to curb the rise of syphilis, gonorrhea, non-gonococcal urethritis, chancroid, granuloma inguinale and lymphogranuloma venereum within most of the United States. However, there are still "hot spots" in the southern U.S. and in non-Caucasian and urban populations, and these diseases continue to be prevalent in underdeveloped countries. Molluscum contagiosum and condyloma acuminata are increasing throughout the world. Herpes simplex is in the midst of an epidemic, having increased in the United States by 30% in the last 15 years. The failure of preventive programs to halt or reverse these epidemics stems from a combination of factors involving both patients and the medical profession. Patient and sexual partner ignorance, denial and deliberate deception play an important role. However, healthcare professional ignorance and failure to keep a high index of suspicion are also crucial. These issues are compounded by the quick-visit concept propagated by managed care, which dilutes most educational efforts. Teens particularly suffer from the lack of an unhurried discussion of sexual practices, and the sharp rise in STDs in this population reflects failure in the medical system. This paper will review the classical presentations of the various STDs, and will detail in what ways the coexistence of HIV disease alters clinical appearance and disease progress. Subtle variations in presentations that often lead to misdiagnosis are discussed. Diagnosis and treatment of STDs change rapidly as new developments occur, and the latest recommendations are examined. The ways in which these therapies differ in special need groups such as HIV and pregnancy are specifically detailed. The goal of this review is to arm the clinician with all of the necessary ingredients for timely and accurate diagnosis and treatment, as well as ways to assist the patient in dealing with these difficult topics. Patient education is highlighted, as it, along with practitioner expertise, is the key to disease eradication. We are the missing link in STD eradication.

The hormone continuum: accrual of women's health benefits.

Abstract: The hormone continuum is a treatment strategy that advocates maintaining hormone continuity, from the reproductive years into menopause and beyond. This entails the use first of oral contraceptives (OCs), which confer well-known health benefits--especially reductions in ovarian and endometrial cancers--besides effective contraception, and later, hormone replacement therapy (HRT), which provides relief of perimenopausal and menopausal symptoms and protects older women from (a) decreasing bone mineral density; (b) cardiovascular disease, according to several studies; and (c) Alzheimer's disease, as suggested by a number of studies. In perimenopause, use of OCs declines by about one-half, and then by a further four-fifths up to menopause. This is unfortunate, because in these later reproductive years women are subject to unintended pregnancy, which in 65% of cases is terminated by abortion. Furthermore, women are thereby deprived also of alleviation of dysmenorrhea and even vasomotor symptoms that often characterize the perimenopause. After menopause is well established, a "seamless" transition to HRT can be made, often with the same progestin that was contained in the OC. This paper discusses risks as well as benefits of hormone therapy, especially of HRT, with an emphasis on patient counseling and individualizing of therapy.

Breast cancer and HRT--what are the data?

Abstract: Breast cancer remains one of women's greatest concerns. When asked regarding the likelihood of contracting a specific disease, most women believe their greatest risk of death is from breast cancer. Interestingly, we have gone from a time when estrogen was utilized as a treatment regimen in advanced breast cancer, to the current question of hormone replacement therapy increasing the risk of breast cancer. When one searches earlier data, it is noted that estrogen in several different forms, including ethinyl estradiol, as well as DES, was used as a therapeutic agent in the management of advanced breast cancer. Indeed, some of the original trials evaluating tamoxifen for adjunctive treatment of breast cancer used estrogen as the "gold-standard" treatment arm. Numerous publications have attempted to address the relationship between hormone replacement therapy and breast cancer. In the last quarter of a century, at least 50 epidemiological studies have been published, with some studies demonstrating slight increases in patients who used hormone replacement therapy for an extended time, while others demonstrated no evidence of a change in incidence. The "Nurses' Health Study" suggested that current users of hormone replacement therapy of 5 or more years' duration have a relative risk of greater than 1.4. While a well-performed and conceived trial, it suffers from limitations like all other studies. In the same time period, multiple additional studies have cast doubt on the likelihood of hormone replacement therapy markedly increasing the risk of breast cancer. When the multitude of studies is combined, the evidence seems to demonstrate that in ever-use of hormone replacement therapy the increase in relative risk is small. It is interesting that, in almost all studies published (even those demonstrating increases such as the "Nurses' Health Study") discontinuation of 2 to 5 years evaporates the increased risk. This seems biologically implausible, given the prior exposure. A recent study by Sellers et al evaluated over 41,000 patients in a prospective cohort. In this study, they closely evaluated patients who were at a higher risk of breast cancer based on a positive family history in first-degree relatives. Interestingly, they, like others, found that HRT was not associated with a significantly increased incidence of breast cancer, but did note a significantly reduced total mortality rate. When one evaluates the sum total data in the world literature regarding hormone replacement therapy and breast cancer, it is difficult to ascertain that any substantial clinical risk exists with the use of hormone replacement therapy and breast cancer. Multiple ongoing trials, including the Women's Health Initiative-a Prospective Protocol, will help to define better if any appreciable risk exists.

Female reproductive endocrinology at the turn of the millennium.

Abstract: The mainstays of female reproductive endocrinology, even as the millennium occurs and we cite highly technological advances in assisted reproduction, continue to be-as for the past decade-and-a-half-the use of GnRH analogs, both agonists and antagonists; the use of other gonadotropins, both alone and in combination, as well as with other types of drugs; testing for "ovarian reserve," as we attempt infertility treatment for populations that now include more nulliparous women of older reproductive age; and diagnosing and treating polycystic ovarian syndrome (PCOS), for both its reproductive and general health effects, especially as concerns insulin resistance. These topics are covered in detail, with reviews of well-controlled, and sometimes contrasting, studies.

New possibilities for diagnosis and treatment of osteoporosis.

Abstract: Postmenopausal osteoporosis is preventable and treatable. Women need not lose bone mineral density (BMD) after the menopause. Without intervention, all women lose bone after menopause, regardless of the amount of calcium, vitamin D, and exercise they undertake. Postmenopausal women need estrogen replacement, a selective estrogen receptor modulator (SERM), or a bisphosphonate to prevent bone loss. Alendronate, risedronate (bisphosphonates) and raloxifene (SERM) are approved for the prevention of bone loss. The diagnosis of at-risk postmenopausal women can best be accomplished by measuring BMD in all postmenopausal women age 65 years and older regardless of their risk profile and in all postmenopausal women under 65 years with one or more risk factors. Treatment guidelines direct physicians to treat postmenopausal women with T-scores lower than -2.0 SD regardless of their risk profile and postmenopausal women with T-scores lower than -1.5 SD with one or more risk factors. The lower the BMD, the greater the fracture risk, particularly in individuals with increased age, existing fragility fractures, or high bone turnover. The best intervention for a patient should be individually selected, based on careful clinical assessment. Although calcitonin is not approved for prevention, it is approved for treatment. The labeling of estrogens has been modified to state that they may be used to "manage" osteoporosis. The lack of efficacy of calcitonin to prevent bone loss during the first 5 years after menopause, and the lack of prospective fracture reduction data for estrogen, have resulted in these labeling restrictions. Alendronate, risedronate, and raloxifene are currently approved for the treatment of osteoporosis. Both of these compounds have been shown to increase BMD and decrease fracture risk. Monitoring of a patient's response to treatment may be accomplished using serial BMD testing and biomarkers of bone turnover.

A critical assessment of generic substitution for the obstetrician-gynecologist.

Abstract: In the past decade, generic drugs have increased in market share severalfold. There are drugs used in obstetrics/gynecology that are of concern with regard to generic substitution, because they are believed to be well tested and essentially not dangerous. The present review is mainly of the use of generics in oral contraception and assisted reproduction. It seeks to answer the question, whether cost advantages, great or slight, offered by the generics are well worth the attendant need for increased vigilance by clinicians and, possibly, taking care of increased side effects or even mishaps resulting from lack of effectiveness (or excessive "effectiveness"). The discussion is based on the concepts of bioavailability and therapeutic equivalence.

IVF: the new era.

Abstract: In-vitro fertilization (IVF) has made great strides in the past 25 years including the development of micromanipulation techniques. Intracytoplasmic sperm injection (ICSI) for treatment of severe male factor infertility paved the way for the use of the micromanipulator. Micromanipulation techniques are now an integral part of an IVF program and are now also employed to biopsy embryos from patients harboring genetic abnormalities. Micromanipulation has also been used in the development of nuclear transfer techniques--a potential solution for creating "younger" oocytes for women of advanced maternal age and spermatozoa for azoospermic men. Other recent developments include the sequential media enabling the embryo to survive to blastocyst stage and also successful oocyte vitrification to preserve future fertility. This paper describes the latest technologies in in-vitro fertilization and relates them to the total problem of infertility, age-related and otherwise.

Laparoscopic Fertility-Promoting Procedures of the fallopian tube and the uterus.

Abstract: Assisted reproductive technology and reproductive surgery can be complementary, and the feasibility of laparoscopic suturing has facilitated conducting reproductive surgery entirely by laparoscopy. Young women with tubal disease can be offered surgery, whereas older women, with their rapid decline in fertility, are better treated with in vitro fertilization (IVF). IVF should be the first line of treatment for women with a severe degree of hydrosalpinx, or with extensive and dense adhesions. However, the presence of hydrosalpinx decreases IVF pregnancy rates. In those whose hydrosalpinx is seen on ultrasound, especially after failed IVF cycles, a laparoscopic salpingectomy can be done. For tubal anastomosis, the superior results of this procedure are well established. The association between uterine myoma and infertility is unclear. However, in those with a distorted uterine cavity, and no other cause of infertility, myomectomy can be considered; myomectomy can be done by laparoscopy. Because of the risks of uterine rupture, proper closure of the uterine incision is of utmost importance.

Local and systemic options for hormone replacement therapy.

Abstract: Women now have an array of options for hormone replacement therapy (HRT) Yet, the medical practitioner faces many challenges in helping women explore these options Which therapy is right for which woman? What are the risks and benefits of each therapy? Providing hormone replacement therapy entails assessing the individual woman's need for hormone replacement therapy given her cardiovascular health, bone health, vasomotor symptoms, bleeding patterns, and attitudes A woman who chooses to use HRT has many options, including therapies that vary in preparation, dosing schedule, route of administration, and systemic or local effects This paper reviews the variety of preparations Healthcare practitioners now can individualize HRT The challenge is to evaluate, counsel, and treat women in a way that will promote satisfaction, and thus long-term use of HRT

The relationship between the duration of menopause and lower urinary tract symptoms in women aged 40 to 59.

Abstract: Objective-To evaluate lower urinary tract symptoms in pre- and perimenopausal women. Method-Four hundred seventy-one women between 40 and 59 years of age with perimenopausal complaints attending our menopause clinic were evaluated for lower urinary tract symptoms by using the International Prostate Symptom Score questionnaire. The women were categorized by subgroups as being in premenopause, early menopause (1-<5 years' duration) and late menopause (≥5 years' duration), and by decade. Statistical evaluations were done by unpaired t test, one-way ANOVA, and simple and multiple regression analyses. Results-The premenopausal women in their forties had more severe lower urinary tract symptoms when compared with early and late menopausal women. In comparisons the nocturia score tended to rise with age. Conclusion-Lower urinary tract symptoms appear to be affected by both age and the duration of menopause in women in their forties and fifties, and this observation might be taken into consideration while evaluating this age group for lower urinary tract symptoms.

Evaluation of the subfertile couple: the fine points.

Abstract: The basic fertility evaluation depends more on the history than findings at the initial visit. The previous reproductive history of both partners, the duration of infertility in this union, frequency of coitus, and a complete menstrual history often point to the diagnosis and correct therapy. Previous medical records pertaining to the problem are another source of information, and recent studies such as semen analysis results, ultrasound and salpingographic reports should be sought; the actual films are preferable to the reports. Previous surgeries, thought to be unrelated to fertility, may have been performed--try to get the operative report. There are myriad drugs that can interfere with fertility in either gender; therefore, a thorough history of past and present use as well as environmental toxin exposure is necessary. Often the routine prenatal tests for titers against common viral illnesses which can cause fetal damage have not been performed. Specific ethnic groups will need special testing. No invasive test or therapy should be performed on the female partner in the absence of a recent semen analysis. Ovulation evaluation can take the form of a basal body temperature chart; it's free, doesn't hurt, and is accurate in detecting the presence of ovulation, except for the exact timing. The over-the-counter urinary LH detection kits are highly reliable in predicting the actual day of ovulation. Serial ultrasounds to do this are not cost effective. This paper will discuss these points and the commonly performed evaluations such as salpingography and endoscopy. Specific hormonal evaluations of the amenorrheic patient and those with suspected polycystic ovarian syndrome will also be discussed.