Regulatory issues in female sexual dysfunction.

Female sexual dysfunction (FSD) remains an enigmatic area to some, a controversial area to others and the subject of continued, intense debate in the literature. Questions remain regarding the legitimacy of FSD as a bona fide disease; the definition of FSD; the methods of diagnosis; and, the treatment of FSD. In this timely perspective, Jean Fourcroy, Consultant in Urology, Endocrinology and Regulatory Issues, discusses the controversies that continue to plague FSD.

The role of neuromodulation in the management of urinary urge incontinence.

OBJECTIVE: To examine the benefit-risk profile of neuromodulation in treating refractory urinary urge incontinence and other voiding disorders. PATIENTS AND METHODS: The outcome measures from all patients in pivotal clinical trials who had undergone sacral nerve stimulation were analysed retrospectively. RESULTS: Neuromodulation was effective in several clinical studies; the response is durable and the benefit-risk profile good. CONCLUSION: Sacral nerve stimulation is becoming the standard of care for refractory overactive bladder and retention problems. The potential benefit of neuromodulation should be included in female urology and gynaecology training programmes.

Definitions of women's sexual dysfunction reconsidered: advocating expansion and revision.

In light of various shortcomings of the traditional nosology of women's sexual disorders for both clinical practice and research, an international multi-disciplinary group has reviewed the evidence for traditional assumptions about women's sexual response. It is apparent that fullfilment of sexual desire is an uncommon reason/incentive for sexual activity for many women and, in fact, sexual desire is frequently experienced only after sexual stimuli have elicited subjective sexual arousal. The latter is often poorly correlated with genital vasocongestion. Complaints of lack of subjective arousal despite apparently normal genital vasocongestion are common. Based on the review of existing evidence-based research, many modifications to the definitions of women's sexual dysfunctions are recommended. There is a new definition of sexual interest/desire disorder, sexual arousal disorders are separated into genital and subjective subtypes and the recently recognized condition of persistent sexual arousal is included. The definition of dyspareunia reflects the possibility of the pain precluding intercourse. The anticipation and fear of pain characteristic of vaginismus is noted while the assumed muscular spasm is omitted given the lack of evidence. Finally, a recommendation is made that all diagnoses be accompanied by descriptors relating to associated contextual factors and to the degree of distress.

Report of the international consensus development conference on female sexual dysfunction: definitions and classifications.

PURPOSE: Female sexual dysfunction is highly prevalent but not well defined or understood. We evaluated and revised existing definitions and classifications of female sexual dysfunction. MATERIALS AND METHODS: An interdisciplinary consensus conference panel consisting of 19 experts in female sexual dysfunction selected from 5 countries was convened by the Sexual Function Health Council of the American Foundation for Urologic Disease. A modified Delphi method was used to develop consensus definitions and classifications, and build on the existing framework of the International Classification of Diseases-10 and DSM-IV: Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association, which were limited to consideration of psychiatric disorders. RESULTS: Classifications were expanded to include psychogenic and organic causes of desire, arousal, orgasm and sexual pain disorders. An essential element of the new diagnostic system is the "personal distress" criterion. In particular, new definitions of sexual arousal and hypoactive sexual desire disorders were developed, and a new category of noncoital sexual pain disorder was added. In addition, a new subtyping system for clinical diagnosis was devised. Guidelines for clinical end points and outcomes were proposed, and important research goals and priorities were identified. CONCLUSIONS: We recommend use of the new female sexual dysfunction diagnostic and classification system based on physiological as well as psychological pathophysiologies, and a personal distress criterion for most diagnostic categories.

Urogynecology update: incontinence.

Physicians need to be more sensitive to urinary incontinence, because patients are unlikely to introduce the subject unless the symptoms are incapacitating. Failure to discuss the issue prevents patients from taking advantage of the many new drugs and mechanical devices that have become available. The vast majority of cases are treatable, often by relatively simple means.

Flutamide hepatotoxicity.

PURPOSE: Observed and expected reporting rates were compared in patients who died or were hospitalized due to hepatotoxicity associated with the use of flutamide. MATERIALS AND METHODS: Case series were submitted to the MedWatch Spontaneous Reporting System of the Food and Drug Administration. Reporting rates for serious hepatotoxicity due to flutamide were calculated and compared to rates for hospitalized patients with acute idiopathic hepatitis in the medical literature. RESULTS: After the marketing of flutamide in the United States, between February 1989 and December 1994 the Food and Drug Administration received reports of 20 patients who died and 26 who were hospitalized for hepatotoxicity due to flutamide. The rate of approximately 3 per 10,000 flutamide users exceeds by 10-fold or more the expected rate of hospitalizations for acute noninfectious liver injury of 2.5 per 100,000 men 65 years and older. Autopsies in 6 cases revealed marked to massive hepatic necrosis as the predominant feature. CONCLUSIONS: Flutamide is a potent hepatotoxin in certain patients. Serial blood aminotransferase levels should be monitored during the first few months of flutamide treatment. Before beginning use of this drug patients should be instructed to report immediately to physicians any episodes of nausea, vomiting, fatigue and jaundice so that flutamide can be promptly discontinued to avoid progression of possible liver injury.

Women and the development of drugs: why can't a woman be more like a man?

Most health providers and researchers would agree that the FDA provides the finest and safest methods to ensure safety and efficacy for the consumer. All proposed regulations or changes are published in the Federal Register (Title 21 Code of Federal Regulations). The 70 kg white male is no longer considered the norm. Any differences in race, gender, and ethnic composition need to be identified. Accessibility of clinical trial subjects has been a key factor in the inclusion of patients in studies as exemplified by the use of male medical students, male prison subjects, and male Veterans' Administration patients. This is no longer satisfactory; efforts now must be made to encourage and include representative women in each study. Woman scientists must now accept this challenge in education and leadership roles to ensure the proper representation of women in clinical studies.

Fibrous hamartoma of infancy in the genital region: findings in 15 cases.

Fibrous hamartoma of infancy is a benign myofibroblastic proliferation that typically occurs in the axillary or shoulder region of male infants. We describe 15 cases of this condition, which involved the inguinal region in 5, scrotum in 5, spermatic cord in 1, perineum in 1, labium majus in 1, the suprapubic region in 1 and the pubic area in 1. Patient median and mean ages were 10 and 6.7 months, respectively (range 2 to 24). No case was reported to be congenital. Median and mean tumor size was 3 cm. (range 0.5 to 6). The microscopic features were identical to those seen in fibrous hamartoma of infancy occurring in more typical sites and consisted of 3 components: 1) fascicles of myofibroblasts, 2) disorganized mature adipocytes and 3) small rounded primitive mesenchymal cells. Immunohistochemically, the myofibroblastic component expressed muscle specific actin and vimentin, and the primitive component expressed vimentin only. There was no evidence of increased cellular proliferation in the primitive cell component using proliferating cell nuclear antigen antibodies. Of the 15 lesions 1 recurred locally and 14 were apparently cured by local excision. Awareness of this presentation of fibrous hamartoma of infancy may avert misdiagnosis of more aggressive lesions, especially infantile fibromatosis or rhabdomyosarcoma.

Laboratory methods for assessing human semen in epidemiologic studies: a consensus report.

It is clear that additional methodologic work needs to be performed. Some data gaps described above are being actively investigated. Other standards were not addressed at this meeting; statistical handling of the data, differences among CASA machines, and factors to consider as potential confounders in analysis are just a few. These may be the subject of future workshops, which will also review progress made in the existing knowledge base. For now, this effort represents a first attempt to share information and to use it to encourage investigators in different laboratories to employ similar methods. In this way more direct comparisons among studies can be made, and our collective data base can be strengthened.

Food and Drug Administration guidelines for reproductive toxicity testing.

The Food and Drug Administration generally requires reproductive toxicity testing of all new drugs to be used by pregnant women or women or men of reproductive potential. These requirements may vary among the centers within the FDA. Reproductive and developmental toxicity is usually tested in one or two animal species and is divided into three segments to represent treatment throughout the reproductive process. The FDA monitors adverse drug effects on human reproduction through postmarketing surveillance.