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Hypoactive sexual desire disorder is the most common cause of sexual dysfunction in women. According to a national survey, approximately a third of all women experience low sexual desire. The etiology of the disorder is often multifactorial. Research in treatment options for hypoactive sexual desire disorder is limited. In this article, treatment options including sex therapy, hormone therapy (estrogen, testosterone, dehydroepiandrosterone, tibolone), non-hormonal medical therapies (buproprion, buspirone, phosphodiesterase-5 inhibitors, amantadine and apomorphine) and herbal therapies (Avlimil(R), Arginmax(R), Zestra(R), yohimbine and Ginkgo biloba) are reviewed.

Background: Oophorectomy reduces serum testosterone levels. We studied the efficacy and safety of transdermal testosterone in treating hypoactive sexual desire disorder in surgically menopausal women., Methods: A 24-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial was conducted in women (aged 24-70 years) who developed distressful low sexual desire after bilateral salpingo-oophorectomy and hysterectomy and who were receiving oral estrogen therapy. Women were randomized to receive placebo (n = 119) or testosterone patches in dosages of 150 microg/d (n = 107), 300 microg/d (n = 110), or 450 microg/d (n = 111) twice weekly for 24 weeks. Sexual desire and frequency of satisfying sexual activity were primary efficacy outcome measures., Results: Of the 447 women randomized, 318 (71%) completed the trial. Compared with placebo, women receiving the 300-microg/d testosterone patch had significantly greater increases from baseline in sexual desire (67% vs 48%; P = .05) and in frequency of satisfying sexual activity (79% vs 43%; P = .049). The 150-microg/d group showed no evidence of a treatment effect. The 450-microg/d group also was not statistically different from the 300-microg/d or placebo groups. Marginally significant linear dose-response trends were observed for total satisfying sexual activity and sexual desire at 24 weeks (P = .06 and .06, respectively). Adverse events occurred with similar frequency in both groups; no serious safety concerns were observed., Conclusions: The 300-microg/d testosterone patch increased sexual desire and frequency of satisfying sexual activity and was well tolerated in women who developed hypoactive sexual desire disorder after surgical menopause.

Dehydroepiandrosterone (DHEA) therapy is controversial due to sensationalized reports of epidemiologic studies and the over-the-counter availability of DHEA. Human clinical trials have investigated the potential efficacy of DHEA therapy in multiple conditions with resultant inconsistencies in findings. DHEA is unique compared with other adrenal steroids because of the fluctuation in serum levels found from birth into advancing age. The lower endogenous levels of DHEA and DHEA sulfate found in advancing age have been correlated with a myriad of health conditions. Also, some studies suggest gender-specific actions of endogenous and exogenous DHEA. We reviewed only pharmacokinetic studies and human clinical trials investigating the efficacy of DHEA therapy that were placebo-controlled as these provided the most reliable scientific basis for the evaluation of DHEA therapy. Pharmacodynamic studies suggest that doses of 30-50mg of oral DHEA may produce physiologic androgen levels, especially in women. These studies report a dose-dependent effect and lack of accumulation of serum androgen levels. Pharmacologic studies also reveal a gender-specific response to DHEA therapy such that testosterone levels are increased in women but not in men. Clinical trials suggest that 50mg of oral DHEA, but not <30mg, can increase serum androgen levels to within the physiologic range for young adults with primary and secondary adrenal insufficiency, possibly improve sexual function, improve mood and self-esteem, and decrease fatigue/exhaustion. Whereas DHEA replacement therapy may be effective in treating patients with adrenal insufficiency, human clinical trials investigating its efficacy in conditions such as systemic lupus erythematosus, HIV, Alzheimer disease, advancing age, male sexual dysfunction, perimenopausal symptoms, depression, and cardiovascular disease have not provided consistent findings.

Background: The role of angiotensin-receptor blockers (ARBs) in treating patients with chronic heart failure and high-risk acute myocardial infarction (MI) has been controversial, and recent clinical trials provide more information on this topic., Purpose: To quantify the effect of ARBs when compared with placebo (with and without background angiotensin-converting enzyme [ACE] inhibitors) and ACE inhibitors on all-cause mortality and heart failure hospitalizations in patients with chronic heart failure and high-risk acute MI., Data Sources: Data from original research published through 13 November 2003., Study Selection: Predefined criteria were used to identify 24 trials., Data Extraction: 2 reviewers independently collected information on study characteristics and data on all-cause mortality and heart failure hospitalization., Data Synthesis: 24 trials involving 38 080 patients were included. Analysis of chronic heart failure trials revealed that 1) ARBs were associated with reduced all-cause mortality (odds ratio [OR], 0.83 [95% CI, 0.69 to 1.00]) and heart failure hospitalizations (OR, 0.64 [CI, 0.53 to 0.78]) as compared with placebo; 2) for ARBs versus ACE inhibitors, all-cause mortality (OR, 1.06 [CI, 0.90 to 1.26]) and heart failure hospitalization (OR, 0.95 [CI, 0.80 to 1.13]) did not differ; 3) and for combinations of ARBs plus ACE inhibitors versus ACE inhibitors alone, all-cause mortality was not reduced (OR, 0.97 [CI, 0.87 to 1.08]) but heart failure hospitalizations were reduced (OR, 0.77 [CI, 0.69 to 0.87]). For patients with high-risk acute MI, 2 randomized trials compared ARBs with ACE inhibitors but did not reveal differences in all-cause mortality or heart failure hospitalization., Limitations: Comparative economic data between ARBs and ACE inhibitors are lacking., Conclusions: Because ACE inhibitors and ARBs do not differ in efficacy for reducing all-cause mortality and heart failure hospitalizations in patients with chronic heart failure and in patients with high-risk acute MI, ARBs should be regarded as suitable alternatives to ACE inhibitors.

Purpose: Accurate classification of menopausal status is important to epidemiological research evaluating the role of reproductive hormones in disease processes. Algorithms relying on repeat hormone assays are unfeasible in large epidemiological studies. This paper summarizes the development of the Women's Ischemia Syndrome Evaluation (WISE) Hormonal menopausal status algorithm for determining premenopausal, perimenopausal, and postmenopausal status using menstrual and reproductive history and reproductive hormone levels obtained at a single clinic visit., Methods: The authors compared the accuracy of this algorithm with two currently used self-report algorithms: Menstrual, based only on months since last menstrual period, and Historical, which adds age and surgical history., Results: The study population consisted of 515 women (329 clearly postmenopausal) enrolled in the WISE study who were undergoing coronary angiography for suspected ischemia. A subgroup of 186, not clearly postmenopausal, was classified by these three algorithms. Results were evaluated against individualized expert consensus classification. The Menstrual and Historical classifications differed significantly (p < 0.0001) from expert consensus, with 32%-26% discordant classifications, respectively. For the WISE Hormonal classification, discordance was 4%., Conclusions: The authors conclude that inaccurate classifications of menopausal status occur frequently in self-report algorithms. Use of the relatively simple WISE algorithm can improve the accuracy of menopausal status classification for epidemiological research.

Objective: Review of literature with regard to androgen replacement therapy in women., Design: Review of the MEDLINE database and references from articles., Conclusions: Androgens affect sexual function, bone health, muscle mass, body composition, mood, energy, and the sense of well-being. Androgen insufficiency clearly has been demonstrated in patients with hypopituitarism, adrenalectomy, oophorectomy, and in some women placed on oral estrogen therapy which increases sex hormone-binding globulin (SHBG) levels and lowers the free and bioavailable forms of T. Symptoms of androgen insufficiency in women may include a diminished sense of well-being, low mood, fatigue, and hypoactive sexual desire disorder with decreased libido, or decreased sexual receptivity and pleasure that causes a great deal of personal distress. The preponderance of evidence from clinical trials supports the correlation of decreased endogenous androgen levels with these symptoms and alleviation of many of the symptoms with the administration of T or, in some cases, DHEA. There are no Food and Drug Administration-approved androgen preparations on the market for treating androgen insufficiency in women. The safety profile of androgens in doses used for the treatment of hypoactive sexual desire disorder has been excellent with only mild acne and hirsutism being noted in a minority of patients.

A 59-year-old African American male with a remote history of Graves' disease presented with a 13-cm sacrococcygeal mass that was resected. Pathologic examination revealed this to be papillary thyroid carcinoma with large areas of hemorrhage and necrosis. No other teratomatous elements were identified. The patient underwent extensive evaluation of the thyroid gland with ultrasound, computed tomography (CT) scan, and laboratory studies without any evidence of thyroid mass or malignancy. In addition, further evaluations with chest/abdominal/pelvic CT as well as a bone scan failed to reveal any evidence of metastatic disease. At 1-year follow-up, the patient has remained euthyroid and without evidence of recurrence. We believe that our patient may represent the first reported case of malignant transformation of mature thyroid tissue in a sacrococcygeal teratoma. The impact of his diagnosis on the decision-making for performing a total thyroidectomy is discussed.

Debates regarding thyroid stunning-a phenomenon whereby a diagnostic dose of radioiodine decreases uptake of a subsequent therapeutic dose by remnant thyroid tissue or by functioning metastases-have been fueled by inconsistent research findings. Quantitative studies evaluating radioiodine uptake and qualitative studies using visual observations both compare thyroid function on the diagnostic scan (DxSCAN) versus the posttreatment whole-body scan (RxWBS). The variability of findings may be the result of a lack of consensus in clinical nuclear medicine regarding many parameters of radioiodine usage including the need to obtain a pretreatment diagnostic scan, appropriate therapeutic dose, time between therapy dose administration and DxSCAN, and how successful ablation is measured. In the studies considered in this review, those that used (123)I rather than (131)I for DxSCAN, allowed less time to elapse between diagnostic and therapy dose, and more time between therapy dose and RxWBS (at least 1 week), did not observe stunning. However, groups that recognized stunning did not demonstrate any difference in outcomes (determined by successful first-time ablation). Whether stunning is a temporary phenomenon whereby stunned tissue eventually rejuvenates, or whether observed stunning actually constitutes "partial ablation," is yet to be delineated.

Objectives: We sought to evaluate hypoestrogenemia of hypothalamic origin and its association with angiographic coronary artery disease (CAD) in premenopausal women., Background: Coronary artery disease in premenopausal women appears to have a particularly poor prognosis. Primate animal data suggest that premenopausal CAD is strongly determined by psychosocial stress-induced central disruption of ovulatory cycling and resulting hypoestrogenemia., Methods: We assessed reproductive hormone blood levels and angiographic CAD using core laboratories in 95 premenopausal women with coronary risk factors who were enrolled in the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation and were undergoing coronary angiography for evaluation for suspected ischemia., Results: Premenopausal women with angiographic CAD (n = 13) had significantly lower estradiol, bioavailable estradiol, and follicle-stimulating hormone (FSH) (all p < 0.05) than women without angiographic CAD (n = 82), even after controlling for age. Hypoestrogenemia of hypothalamic origin, defined as estradiol <184 pmol/l (50 pg/ml), FSH <10 IU/l, and luteinizing hormone <10 IU/l, was significantly more prevalent among the women with CAD than those without CAD (9/13 [69%] vs. 24/82 [29%], respectively, p = 0.01). Hypoestrogenemia of hypothalamic origin was the most powerful predictor of angiographic CAD in a multivariate model (odds ratio [OR] 7.4 [confidence interval (CI) 1.7 to 33.3], p = 0.008). Anxiolytic/sedative/hypnotic and antidepressant medication use were independent predictors of hypoestrogenemia of hypothalamic origin in a multivariate model (OR 4.6 [CI 1.3 to 15.7], p = 0.02, OR 0.10 [CI 0.01 to 0.92], p = 0.04, respectively)., Conclusions: Among premenopausal women undergoing coronary angiography for suspected myocardial ischemia, disruption of ovulatory cycling characterized by hypoestrogenemia of hypothalamic origin appears to be associated with angiographic CAD.

Purpose: Reproductive hormones such as estrogen, progesterone, and testosterone are synthesized from a common cholesterol precursor pathway. We hypothesized that use of statins and the resultant lower blood lipoprotein levels would be associated with lower reproductive hormone levels in women. We also sought to evaluate this association, independent of statin use, particularly among premenopausal women of childbearing age., Methods: We enrolled 453 (114 pre-, 30 peri-, and 309 postmenopausal) women with coronary risk factors (mean [+/- SD] age, 58 +/- 13 years) who were undergoing coronary angiography for suspected ischemia at four academic medical centers. Blood lipoprotein levels (total cholesterol, triglycerides, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein cholesterol) and serum reproductive hormone levels (estradiol, bioavailable estradiol, estrone, progesterone) were measured., Results: Use of statins was associated with lower lipoprotein levels, but not lower reproductive hormone levels, in all women. Mean estradiol levels were not significantly lower among premenopausal women with very low LDL cholesterol levels compared with women with higher LDL cholesterol levels (estradiol: 71 +/- 52 pg/mL vs. 88 +/- 67 pg/mL, P = 0.32)., Conclusion: Among women undergoing coronary angiography for suspected myocardial ischemia, the use of statins, or lower cholesterol levels, are not associated with significantly lower levels of reproductive hormones.

False-positive serum human chorionic gonadotropin results are estimated to occur in 1 in 10(3) to 1 in 10(4) tests. Most of these false-positive results are due to interference by non-human chorionic gonadotropin substances (especially human luteinizing hormone and anti-animal immunoglobulin antibodies) and the detection of pituitary human chorionic gonadotropin. The false-positive human chorionic gonadotropin measurements are characterized by serum levels that are generally <1000 mIU/mL, the absence of human chorionic gonadotropin in the urine, nonparallelism of the human chorionic gonadotropin levels in serial dilutions of the serum with the human chorionic gonadotropin standard, results that are not consistent with the clinical or operative findings, the absence of a substantial change in the serum levels over time or after therapy, and the finding of a negative result when an alternative type of human chorionic gonadotropin assay is used. An algorithm is presented to aid in the recognition of false-positive human chorionic gonadotropin results in patients.

Critical issues concerning the role of androgens in the physical, sexual, and emotional health of women include the following:1. Which androgens best reflect the androgen status of women? 2. What form of T should be measured and how? 3. Do T levels fall after menopause? 4. What effect does oophorectomy have on T levels? 5. What is the relationship between T and sexual dysfunction? 6. What constitutes androgen insufficiency syndrome? 7. What conditions are associated with androgen insufficiency? 8. How should a patient with suspected androgen insufficiency be evaluated? 9. Does androgen replacement therapy improve sexual dysfunction? 10. Do androgens enhance the quality of life? 11. Is estrogen and androgen therapy superior to estrogen therapy alone for low bone mineral density? 12. What are the indications for androgen replacement therapy? 13. What is the best means for delivery of androgen therapy? 14. How should androgen replacement therapy be monitored? Based on our current knowledge, it is clear that some women develop symptomatic androgen insufficiency and that androgen replacement therapy has a beneficial effect on libido, sexual satisfaction, quality of life, and bone mineralization. Androgen replacement therapy should be given the same consideration that we give estrogen replacement therapy.

Background: Studies show that subspecialists can provide better quality care than primary care physicians when working within their subspecialty for patients with some medical conditions. However, many subspecialists care for patients outside of their chosen subspecialty. The present study compared the quality of care provided by subspecialists practicing outside of their specialty, general internists, and subspecialists practicing within their specialty., Methods: The severity-adjusted mortality rate and the severity-adjusted length of stay were used as indexes of quality of care. Data from 5112 hospital admissions (301 different physicians) for community-acquired pneumonia, acute myocardial infarction, congestive heart failure, or upper gastrointestinal hemorrhage at 6 hospitals in the greater Cleveland, Ohio, area were used in this study. The data were severity adjusted with the CHOICE Severity of Illness System., Results: Subspecialists working outside of their subspecialty cared for 25% of hospitalized patients. When comparing patients cared for by subspecialists practicing outside of their subspecialty, severity-adjusted lengths of stay were longer for patients with congestive heart failure (23% longer; 95% confidence interval [CI], 15%-32%), upper gastrointestinal hemorrhage (22% longer; 95% CI, 7%-39%), and community-acquired pneumonia (14% longer; 95% CI, 5%-24%) than for patients cared for by subspecialists practicing within their subspecialty. Patients also had a slightly higher hospital mortality rate when cared for by subspecialists practicing outside of their specialty than by subspecialists practicing within their subspecialty (mortality rate odds ratio, 1.46; P =.047). In addition, patients cared for by subspecialists practicing outside of their subspecialty had longer lengths of stay, and prolongations of stay were observed for patients with congestive heart failure (16% longer; 95% CI, 8%-26%), upper gastrointestinal hemorrhage (15% longer; 95% CI, 2%-30%), and community-acquired pneumonia (18% longer; 95% CI, 9%-28%) than patients cared for by general internists., Conclusions: Subspecialists commonly care for patients outside of their subspecialty, despite the fact that their patients may have longer lengths of stay than those cared for by subspecialists practicing within their specialty or by general internists. In addition, such patients may have slightly higher mortality rates than those cared for by subspecialists practicing within their subspecialty.

Human insulinlike growth factor binding protein-1 (hlGFBP-1) is a secretory protein that modulates the receptor-binding and biological actions of the insulinlike growth factor I (IGF-I). Human endometrium expresses the mRNA for IGFBP-1, and this protein is secreted by the secretory phase and pregnancy endometrium as well as by ovarian granulosa cells in vitro. In this study, we examined the cellular localization of IGFBP-1 in female reproductive tissues by using a purified monoclonal antibody Mab 6303 with an immunoperoxidase technique. Proliferative- and early secretory-phase endometrium as well as all extrauterine tissues except decidualized cells at the implantation site on the ovaries of ovarian pregnancies were negative for IGFBP-1. In midsecretory-phase endometrium, focal staining was first observed in the cytoplasm of glandular epithelial cells, with weaker staining in the stromal cells. In late secretoryphase endometrium, strong immunostaining was observed in predecidualized stromal cells, with weak focal staining remaining in some of the glandular epithelial cells. In early pregnancy, intense staining was detected in the cytoplasm of decidualized stromal cells of zona compacta in each sample, whereas the nondecidualized stromal cells remained unstained. Strong to medium staining was detected simultaneously in the glandular epithelial cells in 70% of the early pregnancy specimens. In term pregnancy, IGFBP-1 was localized in decidual cells of placental bed and decidua parietalis. Immunolocalization of IGFBP-1 to both endometrial epithelial and stromal cells, although only stromal cells express the gene of IGFBP-1 [14], supports the hypothesis of paracrine actions between these cells. The localization of IGFBP-1 to decidualized cells at the extrauterine implantation sites implies its association with decidual differentiation.