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Testosterone deficiency: a key factor in the increased cardiovascular risk to women following hysterectomy or with natural aging?

The ovaries are a critical source not only of estrogen but also of testosterone. On removal of the uterus, even in instances where ovaries have been spared, their function can be compromised. Women who have had a simple hysterectomy (ovaries remaining intact), even if treated postsurgically with supplementary estrogen, have three times the risk of cardiovascular disease compared with women who have not had a hysterectomy. In men, testosterone has been demonstrated to have beneficial fibrinolytic effects and beneficial effects on blood vessel endothelium, in blood sugar and insulin metabolism, and in maintaining coronary artery circulation. Studies on the potential cardiovascular protective effects of physiologic levels of testosterone in women are critically needed. Restoring a physiologic level of testosterone to women after hysterectomy not only can improve quality of life in terms of sexual libido, sexual pleasure, and sense of well-being but also can build bones--and may be a key to protecting cardiovascular health. Women developing testosterone deficiency as a consequence of natural aging/menopause may similarly benefit from physiologic testosterone supplementation.

Aged↗

Differentiation of postpartum thyrotoxicosis by serum thyroglobulin: usefulness of a new multisite immunoradiometric assay.

Destruction-induced thyrotoxicosis and Graves' thyrotoxicosis must be differentiated, since they are treated differently. To find a useful marker, we examined serial changes in serum thyroglobulin (Tg) concentrations in 20 patients with postpartum thyroid disease (9, euthyroid Hashimoto's disease; 11, Graves' disease in remission in early pregnancy). Serum Tg was measured by a new multisite immunoradiometric assay that allows little influence of anti-Tg autoantibodies. Eight women developed destruction-induced thyrotoxicosis 1 to 4 months postpartum, 6 had relapse of Graves' thyrotoxicosis 2 to 4 months postpartum, and 6 remained euthyroid. In destruction-induced thyrotoxicosis, serum Tg 2 months before the onset was 13.3 +/- 11.4 micrograms/L, then clearly increased 1 month before (34.5 +/- 31.9 micrograms/L) and was even higher at the onset of thyrotoxicosis (116.5 +/- 137.1 micrograms/L). In contrast, serum Tg increased only at the onset in Graves' thyrotoxicosis (from 25.9 +/- 25.2 micrograms/L 1 month before to 76.1 +/- 75.3 micrograms/L at the onset, p < 0.05). There was no difference in serum Tg level at the onset between the two disorders. However, when data were expressed as the percent increase from the level one month before, and the cut-off value were taken at 150%, all 7 patients above the cut-off developed destruction-induced thyrotoxicosis, and 6 of 7 below had recurrent Graves' thyrotoxicosis. Thus, serial measurement of serum Tg is useful for the differentiation of destruction-induced thyrotoxicosis from Graves' thyrotoxicosis after delivery.

Adult↗

Serum transferrin receptor: a specific marker of iron deficiency in pregnancy.

BACKGROUND: Current markers of iron deficiency tend to be less reliable in pregnancy. OBJECTIVE: Our aim was to study the usefulness of soluble serum transferrin receptor (sTfR) as a marker for iron deficiency during early and late gestation and to define iron status in 254 pregnant Swedish women. DESIGN: We performed a cross-sectional and longitudinal evaluation of sTfR in comparison with concentrations of serum ferritin and hemoglobin in blood collected around gestational weeks 11 and 36. RESULTS: The specificity of sTfR was 100%. The sensitivity in relation to both anemia and depleted iron stores was approximately 70%, but this figure is less reliable because of few samples. sTfR in early pregnancy was low: 11% of women had a value below the reference interval. sTfR increased significantly from early to late pregnancy even in the group of women with persisting iron stores. In late pregnancy, 14% of women developed tissue iron deficiency and 5% had iron deficiency according to a combination of all 3 markers. CONCLUSIONS: sTfR seems to be a specific and sensitive marker of iron deficiency in pregnancy and may have advantages over serum ferritin and hemoglobin. The low sTfR concentration in early gestation seems to be caused by reduced erythropoiesis, whereas the increase from early to late pregnancy reflects increased erythropoiesis, and in case of iron deficiency, also tissue iron deficiency. Further studies are needed to verify whether decreased erythropoiesis reduces the possibility of detecting iron deficiency during early gestation by sTfR.

Anemia↗

Malignant angioendotheliomatosis. An angiotropic lymphoma?

A 61-year-old women developed progressive neurologic deficits and died with pneumonia and septicemia. An autopsy demonstrated the characteristic intravascular and focal perivascular infiltrate of malignant angioendotheliomatosis (MAE) throughout the body but concentrated in the central nervous system and skin. Ultrastructurally, the neoplastic cells lacked evidence of endothelial differentiation. Immunohistochemical studies showed focal staining for Factor VIII-related antigen, probably on a nonspecific basis, negative staining for Ulex europaeus I lectin (an endothelial cell marker), and intense staining for leukocyte common antigen. The authors' observations provide evidence that at least some examples of MAE are unusual, angiotropic lymphoid neoplasms.

Antigens↗

Incidence of and risk factors for asymptomatic peripheral arterial occlusive disease: a longitudinal study.

The current study describes the age- and sex-specific incidence rates and risk factors for asymptomatic and symptomatic peripheral arterial occlusive disease (PAOD) among 2,327 subjects and the incidence of intermittent claudication in asymptomatic PAOD subjects. The study population was selected from 18 general practice centers in the Netherlands. PAOD was assessed with the ankle-brachial blood pressure index, and intermittent claudication was assessed with a modified version of the Rose questionnaire. After 7.2 years, the overall incidence rate for asymptomatic PAOD, using the person-years method, was 9.9 (95% confidence interval (CI): 7.3, 18.8) per 1,000 person-years at risk. The rate was 7.8 (95% CI: 4.9, 20.3) for men and 12.4 (95% CI: 7.7, 24.8) for women. For symptomatic PAOD, the incidence rate was 1.0 (95% CI: 0.7, 7.5) overall, 0.4 (95% CI: 0.3, 10.0) for men, and 1.8 (95% CI: 1.0, 10.3) for women. Multivariate analyses showed that increasing age, smoking, hypertension, and diabetes mellitus were the most important risk factors. The overall incidence rate for intermittent claudication among PAOD subjects who were asymptomatic at baseline was 90.5 per 1,000 person-years at risk (95% CI: 36.4, 378.3). The incidence of asymptomatic PAOD was higher than the incidence of symptomatic PAOD, with women developing PAOD more often than men. In the development of preventive strategies, modification of atherosclerotic risk factors, such as smoking, hypertension, and diabetes, should be the main goals.

Adult↗

Human papillomaviruses and cervical cancer in Bangkok. III. The role of husbands and commercial sex workers.

Between September 1991 and September 1993, husbands of women with and without cervical neoplasia and commercial sex workers in one brothel and one massage parlor in Bangkok, Thailand, were interviewed; serologic tests for sexually transmitted infections were performed; and cervical and penile scrapings were tested for human papillomavirus (HPV) DNA. The risks of cervical carcinoma in monogamous women and of oncogenic HPV in their husbands were associated with the men's having unprotected intercourse with prostitutes. The prevalence of oncogenic HPV was higher in commercial sex workers than in women attending gynecologic and family planning clinics. Oncogenic HPV prevalence declined with age in human immunodeficiency virus (HIV)-negative, but not in healthy HIV-positive, commercial sex workers and was weakly associated with hepatitis B antigenemia, suggesting that persistence of HPV infection is due to subtle changes in immunity. Associations of HPV with recent pregnancy and oral contraceptive use suggest that hormonal factors may increase the risk of cervical neoplasia by enhancing persistence of HPV infection. The prevalence of high-grade squamous intraepithelial lesions was strongly related to oncogenic HPV types and weakly to HIV infection only in their presence. Commercial sex workers in Bangkok are reservoirs of oncogenic HPV, and cervical cancer in monogamous Thai women develops in part as a result of transmission of these viruses to them by their husbands from prostitutes.

Adolescent↗

In situ localization of mRNA for the fibrinolytic factors uPA, PAI-1 and uPAR in endometriotic and endometrial tissue.

Endometriotic tissue grows invasively. The plasminogen-activating system is suggested to participate in degradation of extracellular matrix (ECM) and modulation of cell adhesion and migration. We have previously demonstrated elevated levels of the fibrinolytic factors urokinase plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1) in endometriotic tissue and endometrium from women with endometriosis. The aim of the present study was to localize the uPA, PAI-1 and urokinase plasminogen activator receptor (uPAR) mRNA in endometriotic tissue and in endometrium both from women with and without endometriosis. With in situ hybridization, we found that uPA mRNA seems to be up-regulated in endometriotic glands and endometrial stroma as well as PAI-1 mRNA in endometriotic and endometrial stroma from women with endometriosis. uPAR mRNA likewise appears to be up-regulated in both glands and stroma in endometriotic tissue and in endometrial glands from patients compared to endometrial glands and stroma from healthy women. These differences might be important for menstrual shedding and adherence of endometrial fragments to peritoneal lining in women developing endometriosis and for the invasive growth of endometriotic tissue.

Endometriosis↗

Prospective study of diet and ovarian cancer.

Evidence on dietary risk factors for ovarian cancer is inconsistent, but some studies have suggested positive associations with dietary fat, lactose, and cholesterol and negative associations with green and yellow vegetable intake. By using information from the Iowa Women's Health Study, the authors investigated the association of epithelial ovarian cancer with dietary factors in a prospective study of 29,083 postmenopausal women. Dietary information was ascertained via a food frequency questionnaire mailed to participants in 1986. During 10 years of follow-up (1986-1995), 139 of the women developed incident epithelial ovarian cancer. Incidence of the disease was not associated with dietary fat intake. Lactose and cholesterol showed moderately elevated risks. Multivariable-adjusted relative risks for the lowest to highest quartiles of lactose intake were 1.00, 1.38, 1.25, and 1.60 (p for trend = 0.12). For cholesterol, the corresponding values were 1.00, 1.34, 1.86, and 1.55 (p for trend = 0.06). Consumption of eggs was also associated with an increased risk of ovarian cancer. Multivariable-adjusted relative risks for increasing frequency of egg consumption were 1.00 (<1/week), 1.12 (1/week), 2.04 (2-4/week), and 1.81 (>4/week) (p for trend = 0.04). Total vegetable intake was modestly and inversely associated with the risk of ovarian cancer (p for trend = 0.21). Green leafy vegetable intake was more strongly associated with a decreased risk: multivariable-adjusted relative risks for the lowest to highest intake levels were 1.00, 0.80, 0.87, and 0.44 (p = 0.01). These findings are generally in agreement with the results from previous, mostly case-control studies of diet and epithelial ovarian cancer.

Aged↗

Chapter 18: Statistical issues in the design and analysis of studies of human papillomavirus and cervical neoplasia.

Appropriately sophisticated statistical approaches are crucial for addressing the increasingly complex set of critical questions that follow from the recognition that human papillomavirus (HPV) is a necessary causal factor for cervical cancer. Cervical cancer researchers have defined the major stages of cervical carcinogenesis, with HPV infection as the necessary cause. Focus of etiologic studies is shifting from establishing causality to determining risk factors for HPV persistence and neoplastic progression using serially collected biomarkers. Prevention-oriented epidemiology and trials of new screening strategies and vaccines will rely on surrogate endpoints because we cannot let women develop cancer when it can be prevented. Future epidemiologic and prevention studies of HPV infection and cervical carcinogenesis will exploit subtle pathologic distinctions and will employ improved measurements of complex molecular biologic phenomena. The anticipated statistical issues are highlighted in this discussion.

Case-Control Studies↗

Postirradiation pseudosclerodermatous panniculitis.

Pseudosclerodermatous panniculitis is an unusual variant of panniculitis that results as a complication of megavoltage radiotherapy. Four women developed this unusual entity on the anterior chest and abdominal skin after receiving megavoltage therapy for either breast carcinoma or painful bone metastases from breast carcinoma. Histopathologically, the epidermis and dermis of the involved area showed little or no evidence of radiodermatitis. The main findings were confined to the subcutaneous tissue and consisted of thickened, sclerotic septa composed of both thick and thin collagen bundles, and a lobular panniculitis characterized by lipophagic granulomas and scattered lymphocytes and plasma cells. Additionally, one of the cases showed markedly dilated vascular spaces with the appearance of lymphatics in the upper part of the dermis. Pseudosclerodermatous panniculitis after irradiation is an unusual cutaneous complication of megavoltage radiotherapy that should be distinguished from subcutaneous metastatic disease, cellulitis, or connective tissue diseases involving the subcutaneous fat. The differential diagnosis can be established on the basis of the characteristic histopathologic features of postirradiation pseudosclerodermatous panniculitis.

Adult↗

Screening for breast cancer.

Mammography is of real assistance to the surgeon in evaluating breast problems not associated with a breast mass. Use of mammography in the detection of early breast cancer in breast demonstration projects has brought forth the time honored value judgement of benefit vs risk. This report introduces an additional aspect in the consideration of benefit vs risk, the interval cancer. From the demonstration project at KUMC, 326 biopsies were performed and 65 proved to be cancer. However, 24 additional women developed cancer before their next recommended screening date. This reduces the accuracy of mammography and physical examination by trained nurses in screening for breast cancer to 73%.

Adult↗

A personal experience with 100 consecutive total colectomies and straight ileoanal endorectal pull-throughs for benign disease of the colon and rectum in children and adults.

In 1974 total colectomy and ileoanal straight endorectal pull-through (ERPT) were first used at our institution for the definitive management of total colonic Hirschsprung's disease in infants and children. Early success with this operation encouraged us to use this procedure in children and adults with ulcerative colitis and familial polyposis in 1977. Since 1974 we have performed total colectomy and straight ileoanal ERPT on 100 consecutive patients with ulcerative colitis (79), familial polyposis (19), and total colonic Hirschsprung's disease (10). Patients who have undergone a colectomy and ERPT but have not had their temporary ileostomy closed have been excluded from this report. This group of patients represents the only large series of straight ERPTs available for comparison with the various reservoir modifications that have been reported. All operations were performed under the direction of the author. The mean age at surgery was 20.6 +/- 9.8 years, with a range of 1 to 48 years. Forty-six patients were younger than 18 years at the time of operation. All patients with ulcerative colitis and familial polyposis underwent a temporary loop ileostomy with total abdominal colectomy with ERPT; the 10 infants and children with Hirschsprung's disease underwent the total colectomy and ERPT without a back-up ileostomy. There were two deaths in this series, one from fulminate hepatic failure in the late postoperative period and the other from multiple bowel fistulas and sepsis in a teenager with Crohn's disease, in whom the initial diagnosis was ulcerative colitis. Follow-up has ranged from 3 months to 15 years. There were 13 cases of adhesive bowel obstruction, seven of which required an enterolysis. Pelvic sepsis occurred in three patients, two of whom required operative drainage. Two women developed rectovaginal fistulas, which healed with temporary diversion. Minor wound infections occurred in five patients. There were no anastomotic leaks, nor were any cases of pouchitis encountered. In five patients permanent conversion to a Brooke ileostomy was required. Mean stool frequency 3 years after surgery was 7.7 per 24 hours. Daytime continence was achieved in all patients. Occasional nocturnal soiling occurred in 11.1% of patients at 1 year and was absent by 3 years. Neither age nor diagnosis (ulcerative colitis versus familial polyposis) affected stool frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Pelvic inflammatory disease: how should it be managed?

PURPOSE OF REVIEW: To review the published literature on pelvic inflammatory disease over the past year and put into context the major findings. RECENT FINDINGS: remains the commonest identified cause of pelvic inflammatory disease, and yet our understanding of how it causes mucosal damage and the factors explaining why only a subgroup of women develop pelvic inflammatory disease are not known. The increasing evidence for a chlamydial toxin may help to explain how tissue damage occurs and the indolent nature of many chlamydial infections. The evidence for as an important sexually transmitted cause of pelvic inflammatory disease is growing, with implications for treatment regimens and diagnostic testing. Power Doppler ultrasound has been reported to be both sensitive and specific in diagnosing pelvic inflammatory disease, although larger studies are needed to confirm these early results. Outpatient treatment with cefoxitin and doxycycline appears to be as effective when given in an outpatient setting compared with inpatient management with the same agents in a large randomized controlled trial with almost 3 years' follow-up. SUMMARY: There remain many gaps in our knowledge of pelvic inflammatory disease, but the reviewed studies increase our understanding of the pathogenesis of infection, and offer the possibility of better diagnosis and reassurance about the long-term success of antibiotic treatment.

Centers for Disease Control and Prevention, U.S.↗

Spontaneous remission of Cushing syndrome after termination of pregnancy.

A 27-year-old women developed Cushing syndrome during pregnancy. The course of pregnancy was characterized by abnormally low urine and plasma estrogen levels despite the presence of a living fetus. The signs and symptoms of Cushing syndrome disappeared spontaneously within 2 months after delivery. Hormonal studies, however, suggested the presence of an adrenal tumor. An adrenocortical adenoma was found at surgery and removed.

Adenoma↗

Serum prolactin levels following augmentation mammaplasty.

A prospective study to evaluate the possible relationship between augmentation mammaplasty, a chronic irritant to the breast, and serum prolactin levels was carried out. Eleven healthy female subjects were studied. Serum prolactin levels were determined twice prior to surgery and at 1 and 3 weeks after surgery. No significant change was detected in the postoperative prolactin values. In four subjects evaluated 3 months following surgery, the prolactin levels also remained unchanged. In addition, none of the women developed galactorrhea during their observation period. These results suggest that the placement of a Silastic implant for augmentation mammaplasty may not be a chronic stimulus leading to either galactorrhea or elevation of prolactin levels.

Adult↗

Acute macular neuroretinopathy following intravenous sympathomimetics.

Three young women developed acute macular neuroretinopathy with persistent paracentral scotomas following acute hypertension caused by intravenous sympathomimetics. The temporal relationship of the acute onset of symptoms suggests either acute hypertension or a direct retinal effect of sympathomimetics as the cause of the retinal changes.

Acute Disease↗

Symptomatic carpal tunnel syndrome after orthotopic liver transplantation: a retrospective analysis.

BACKGROUND: Carpal tunnel syndrome (CTS) is an entrapment neuropathy of the median nerve and has been reported after renal transplantation; there are no reports of CTS after liver transplantation. METHODS: The incidence of and the risk factors for CTS were assessed in 1350 liver allograft recipients. RESULTS: Seventeen women and two men with CTS were identified. Women developed symptoms at a median time of 6.8 months, and all but one received transplants because of primary biliary cirrhosis (PBC). All 17 patients were taking cyclosporine. The only risk factor for CTS was the pretransplant diagnosis of PBC (6.7% of 240 PBC patients surviving 6 months or more compared with 0.4% of 717 patients who received grafts for other indications). CONCLUSIONS: CTS may occur in patients early after liver transplantation; because in many cases the symptoms were attributed to cyclosporine neurotoxicity, the diagnosis should be considered, especially in patients who received grafts because of PBC.

Aged↗

An earlier age of breast cancer diagnosis related to more frequent use of antiperspirants/deodorants and underarm shaving.

Breast cancer incidence suggests a lifestyle cause. A lifestyle factor used near the breast is the application of antiperspirants/deodorants accompanied by axillary shaving. A previous study did not support a link with breast cancer. If these habits have a role in breast cancer development, women using antiperspirants/deodorants and shaving their underarms frequently would be expected to have an earlier age of diagnosis than those doing so less often. An earlier age of diagnosis would also be expected in those starting to use deodorants and shaving at an earlier age. This is the first study to investigate the intensity of underarm exposure in a cohort of breast cancer survivors. Four hundred and thirty-seven females diagnosed with breast cancer were surveyed. Once grouped by their frequency of underarm hygiene habits, the mean age of diagnosis was the primary end point. Secondary end points included the overall frequency of these habits, and potential usage group confounding variables were evaluated. All statistical tests were two-sided. Frequency and earlier onset of antiperspirant/deodorant usage with underarm shaving were associated with an earlier age of breast cancer diagnosis. Combined habits are likely for this earlier age of diagnosis. In conclusion, underarm shaving with antiperspirant/deodorant use may play a role in breast cancer. It is not clear which of these components are involved. Reviewed literature insinuates absorption of aluminium salts facilitated by dermal barrier disruption. Case-controlled investigations are needed before alternative underarm hygiene habits are suggested.

Adult↗