Candace S. Brown

THE FEMALE SEXUAL FUNCTION INDEX (FSFI): A MULTIDIMENSIONAL SELF-REPORT INSTRUMENT FOR THE ASSESSMENT OF FEMALE SEXUAL FUNCTION

This article presents the development of a brief, self-report measure of female sexual function. Initial face validity testing of questionnaire items, identified by an expert panel, was followed by a study aimed at further refining the questionnaire. It was administered to 131 normal controls and 128 age-matched subjects with female sexual arousal disorder (FSAD) at five research centers. Based on clinical interpretations of a principal components analysis, a 6- domain structure was identified, which included desire, subjective arousal, lubrication, orgasm, satisfaction, and pain. Overall test-retest reliability coefficients were high for each of the individual domains (r=0.79 to 0.86) and a high degree of internal consistency was observed (Cronbach’s alpha values of 0.82 and higher) Good construct validity was demonstrated by highly significant mean difference scores between the FSAD and control groups for each of the domains (p<0.001). Additionally, divergent validity with a scale of marital satisfaction was observed. These results support the reliability and psychometric(as well as clinical) validity of the Female Sexual Function Index (FSFI) in the assessment of key dimensions of female sexual function in clinical and nonclinical samples. Our findings also suggest important gender differences in the patterning of female sexual function in comparison with similar questionnaire studies in males.This article presents the development of a brief, self-report measure of female sexual function. Initial face validity testing of questionnaire items, identified by an expert panel, was followed by a study aimed at further refining the questionnaire. It was administered to 131 normal controls and 128 age-matched subjects with female sexual arousal disorder (FSAD) at five research centers. Based on clinical interpretations of a principal components analysis, a 6-domain structure was identified, which included desire, subjective arousal, lubrication, orgasm, satisfaction, and pain. Overall test-retest reliability coefficients were high for each of the individual domains (r = 0.79 to 0.86) and a high degree of internal consistency was observed (Cronbachs alpha values of 0.82 and higher) Good construct validity was demonstrated by highly significant mean difference scores between the FSAD and control groups for each of the domains (p < or = 0.001). Additionally, divergent validity with a scale of marital satisfaction was observed. These results support the reliability and psychometric (as well as clinical) validity of the Female Sexual Function Index (FSFI) in the assessment of key dimensions of female sexual function in clinical and nonclinical samples. Our findings also suggest important gender differences in the patterning of female sexual function in comparison with similar questionnaire studies in males.

Testosterone patch for low sexual desire in surgically menopausal women: a randomized trial.

OBJECTIVE: To assess the efficacy and safety of a 300 μg/d testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women on concomitant estrogen therapy. METHODS: Five hundred thirty-three women with hypoactive sexual desire disorder who had undergone previous hysterectomy and bilateral oophorectomy were enrolled in a 24-week, multicenter, double-blind, placebo-controlled trial. Patients were randomly assigned to receive placebo or the testosterone patch twice weekly. The primary efficacy endpoint was change from baseline at week 24 in the frequency of total satisfying sexual activity, measured by the Sexual Activity Log. Secondary measures included sexual desire using the Profile of Female Sexual Function and personal distress as measured by the Personal Distress Scale. Hormone levels, adverse events, and clinical laboratory measures were reviewed. RESULTS: Total satisfying sexual activity significantly improved in the testosterone patch group compared with placebo after 24 weeks (mean change from baseline, 1.56 compared with 0.73 episodes per 4 weeks, P = .001). Treatment with the testosterone patch also significantly improved sexual desire (mean change, 10.57 compared with 4.29, P < .001) and decreased personal distress (P = .009). Serum free, total, and bioavailable testosterone concentrations increased from baseline. Overall, adverse events were similar in both groups (P > .05). The incidence of androgenic adverse events was higher in the testosterone group; most androgenic adverse events were mild. CONCLUSION: In surgically menopausal women with hypoactive sexual desire disorder, a 300 μg/d testosterone patch significantly increased satisfying sexual activity and sexual desire, while decreasing personal distress, and was well tolerated through up to 24 weeks of use. LEVEL OF EVIDENCE: I

Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder

Objective: To compare the efficacy of a new low-dose oral contraceptive pill (OCP) formulation with placebo in reducing symptoms of premenstrual dysphoric disorder. Methods: This multicenter, double-blind, randomized clinical trial consisted of 2 run-in and 3 treatment cycles with daily symptom charting; 450 women with symptoms of premenstrual dysphoric disorder were randomized to either placebo or an OCP formulation containing drospirenone 3 mg and ethinyl estradiol 20 &mgr;g. Hormones were administered for 24 days, followed by 4 days of inactive pills (24/4). Results: Scores on the total Daily Record of Severity of Problems decreased by –37.49 in the drospirenone/ethinyl estradiol group and by –29.99 in the placebo group (adjusted mean difference –7.5, 95% confidence interval [CI] –11.2 to –3.8; P < .001 by rank analysis of covariance). Mood symptom scores were reduced by –19.2 and –15.3 in active-treatment and placebo groups, respectively (adjusted mean difference –3.9, 95% CI –5.84 to –2.01; P = .003); physical symptom scores were reduced by –10.7 and –8.6 in active-treatment and placebo groups, respectively (adjusted mean difference –2.1, 95% CI –3.3 to –0.95; P < .001); and behavioral symptom scores were reduced by –7.7 and –6.2 in active-treatment and placebo groups, respectively (adjusted mean difference –1.5, 95% CI –2.251 to –0.727; P < .001). Response, defined as a 50% decrease in daily symptom scores, occurred in 48% of the active-treatment group and 36% of the placebo group (relative risk 1.7, 95% CI 1.1 to 2.6; P = .015) and corresponds to a number-needed-to-treat of 8 patients. Conclusion: A 24/4 regimen of drospirenone 3 mg and ethinyl estradiol 20 &mgr;g improves symptoms associated with premenstrual dysphoric disorder. Level of Evidence: I

Atypical Antipsychotics Part I: Pharmacology, Pharmacokinetics, and Efficacy

OBJECTIVE: To compare the pharmacology, pharmacokinetics, and efficacy of the newer atypical antipsychotics with those of conventional agents and existing atypical agents. DATA SOURCES: Information was retrieved from a MEDLINE English-literature search from July 1986 to June 1998 and by review of references. Indexing terms included neuroleptics, atypical antipsychotics, clozapine, risperidone, olanzapine, sertindole, quetiapine, and ziprasidone. STUDY SELECTION: Comparative studies were selected when possible; placebo-controlled studies were included when data were limited on newer atypical antipsychotics. DATA EXTRACTION: Emphasis was placed on properly designed clinical trials that assessed dosage, expanded efficacy, enhanced adverse effect profile, and cost. DATA SYNTHESIS: Like other atypical antipsychotics, the newer agents have an enhanced 5-hydroxytryptophan/dopaminergic receptors (5-HT2/D2) affinity ratio and undergo extensive biotransformation. Risperidone and olanzapine demonstrate more favorable efficacy/adverse effect ratios than clozapine, sertindole, and conventional antipsychotics in nonrefractory and refractory schizophrenics. Future studies will more clearly define the role of quetiapine and ziprasidone in antipsychotic therapy. CONCLUSIONS: Data from controlled trials on efficacy and extrapyramidal side effects support risperidone or olanzapine as first-line agents for the treatment of schizophrenia. Pharmacologic and pharmacokinetic factors do not distinguish between agents sufficiently for drug selection.

Evaluation of a unique oral contraceptive in the treatment of premenstrual dysphoric disorder.

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS). This is the first trial of a unique oral contraceptive containing a combination of drospirenone (DRSP, 3 mg) and ethinyl estradiol (EE, 30 microg) for the treatment of PMDD. DRSP is a spironolactone-like progestin with antiandrogenic and antimineralocorticoid activity. Spironolactone has been shown to be beneficial in PMS, whereas oral contraceptives have shown conflicting results. In this double-blind, placebo-controlled trial, 82 women with PMDD (Diagnostic and Statistical Manual of Mental Disorders, 4th ed. [DSM IV]) were randomized to receive DRSP/EE or placebo for three treatment cycles. The primary end point was change from baseline in luteal phase symptom scores as assessed on the Calendar of Premenstrual Experiences (COPE) scale. Patients treated with DRSP/EE showed a numerically greater change from baseline compared with those treated with placebo on each of the 22 COPE items and each of the 4 symptom factors. Between-group differences in symptom improvement reached statistical significance in factor 3 only (appetite, acne, and food cravings, p = 0.027). The secondary end points, Beck Depression Inventory (BDI) and Profile of Mood States (PMS), were consistent with the primary end point in that patients treated with the oral contraceptive showed a numerically greater improvement from baseline compared with those treated with placebo. The results of this study show a consistent trend in the reduction of symptoms that suggested a beneficial effect of DRSP/EE for the treatment of PMDD, despite limitations of the study design.

Towards a consensus on diagnostic criteria, measurement and trial design of the premenstrual disorders : the ISPMD Montreal consensus

Premenstrual disorders (PMD) are characterised by a cluster of somatic and psychological symptoms of varying severity that occur during the luteal phase of the menstrual cycle and resolve during menses (Freeman and Sondheimer, Prim Care Companion J Clin Psychiatry 5:30–39, 2003; Halbreich, Gynecol Endocrinol 19:320–334, 2004). Although PMD have been widely recognised for many decades, their precise cause is still unknown and there are no definitive, universally accepted diagnostic criteria. To consider this issue, an international multidisciplinary group of experts met at a face-to-face consensus meeting to review current definitions and diagnostic criteria for PMD. This was followed by extensive correspondence. The consensus group formally became established as the International Society for Premenstrual Disorders (ISPMD). The inaugural meeting of the ISPMD was held in Montreal in September 2008. The primary aim was to provide a unified approach for the diagnostic criteria of PMD, their quantification and guidelines on clinical trial design. This report summarises their recommendations. It is hoped that the criteria proposed here will inform discussions of the next edition of the World Health Organisation’s International Classification of Diseases (ICD-11), and the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) criteria that are currently under consideration. It is also hoped that the proposed definitions and guidelines could be used by all clinicians and investigators to provide a consistent approach to the diagnosis and treatment of PMD and to aid scientific and clinical research in this field.

Atypical Antipsychotics: Part II Adverse Effects, Drug Interactions, and Costs

OBJECTIVE: To compare the adverse effects, drug interactions, and costs of conventional and atypical agents, and to provide a summary of therapeutic guidelines. Part I compared the pharmacology, pharmacokinetics, and efficacy of atypical and conventional agents. DATA SOURCES: Information was retrieved from a MEDLINE English-language literature search from June 1986 to June 1998 and by review of references. Indexing terms included atypical antipsychotics, neuroleptics, clozapine, risperidone, olanzapine, sertindole, quetiapine, and ziprasidone. STUDY SELECTION: Comparative studies were selected when possible; placebo-controlled studies were included when data were limited on newer atypical antipsychotics. DATA EXTRACTION: Emphasis was placed on properly designed clinical trials that assessed dosage, expanded efficacy, enhanced adverse effect profile, and cost. DATA SYNTHESIS: Significant adverse effects are agranulocytosis with clozapine, dose-dependent extrapyramidal side effects (EPS) with risperidone, and neuroleptic malignant syndrome with clozapine and risperidone. Clinically relevant drug interactions may occur with clozapine–lorazepam, clozapine–fluvoxamine, and sertindole– quinidine. Newer atypical agents have high acquisition costs but may reduce noncompliance and rehospitalization rates. CONCLUSIONS: Risperidone or olanzapine are recommended as first-line agents for schizophrenia due to accumulating controlled trials and clinical experience. Quetiapine should be considered with partial response or if EPS develop, and clozapine is an option with treatment-refractory patients. Atypical agents may contribute to a better quality of life, but conventional neuroleptics are the first choice for strictly cost considerations.

Profile of Female Sexual Function: A patient-based, international, psychometric instrument for the assessment of hypoactive sexual desire in oophorectomized women

Objective:The purpose of this study was to develop a self-administered, patient-based questionnaire to assess loss of sexual desire and associated symptoms in postmenopausal women with hypoactive sexual desire disorder (HSDD) experiencing distress. Design:Preliminary items and domains of sexual function were identified through individual and focus group interviews with postmenopausal women in the United States and Europe. A subset of items was selected for translation and further analysis. Cognitive interviews were conducted with women with HSDD and non-HSDD women in eight countries to ensure items would have the same meaning in seven languages. The resulting instrument was tested in 325 oophorectomized women with HSDD and 255 age-matched nonoophorectomized control women in the United States, Canada, Europe, and Australia. Results:Psychometric item reduction analyses resulted in 37 items organized into seven domains characterizing female sexual function in postmenopausal women with HSDD. Excellent reliability and validity of the domains of the Profile of Female Sexual Function (PFSF) were observed in all geographic areas tested. Statistically significant differences between oophorectomized women with low libido and control women were found for all domains and all geographic areas. Conclusions:The PFSF is a new instrument specifically designed for measurement of sexual desire in oophorectomized women with low libido. Robust psychometric properties have been established in a large number of geographic regions and languages, making it useful for assessing therapeutic change in multinational clinical trials.

DEPRESSION AND ANXIETY DISORDERS

Depressive and anxiety disorders are common problems facing obstetrician-gynecologists. Although psychiatric disorders are equally common in men and women, women are at least twice as likely to present with depressive disorders and most anxiety disorders. The depressive disorders include major depression, dysthymia, seasonal affective disorder, and premenstrual dysphoric disorder. The anxiety disorders are panic disorder (with and without agoraphobia), generalized anxiety disorder, social phobia, obsessive compulsive disorder, and PTSD. One must diagnose and manage depressive and anxiety disorders during pregnancy, the purpureum, and while breastfeeding. General treatment principles include assessing suicide risk, psychotherapy, pharmacologic treatment, and an appropriate medical work-up for depressive and anxiety disorders. The SSRIs are the first-line treatment for most depressive and anxiety disorders because of data supporting their efficacy, the minimal need for dosage titration, the overall favorable side-effect profile, and the length of available clinical experience. Newer antidepressants, such as venlafaxine, bupropion, nefazodone, and mirtazapine, are options for patients unresponsive to, or intolerant of, the SSRIs. Treatment considerations include acute, maintenance, and continuation therapy, dosage regimens, adverse effects, and drug interactions. Specific guidelines are available for referring patients to a mental health specialist.

ISPMD consensus on the management of premenstrual disorders

The second consensus meeting of the International Society for Premenstrual Disorders (ISPMD) took place in London during March 2011. The primary goal was to evaluate the published evidence and consider the expert opinions of the ISPMD members to reach a consensus on advice for the management of premenstrual disorders. Gynaecologists, psychiatrists, psychologists and pharmacologists each formally presented the evidence within their area of expertise; this was followed by an in-depth discussion leading to consensus recommendations. This article provides a comprehensive review of the outcomes from the meeting. The group discussed and agreed that careful diagnosis based on the recommendations and classification derived from the first ISPMD consensus conference is essential and should underlie the appropriate management strategy. Options for the management of premenstrual disorders fall under two broad categories, (a) those influencing central nervous activity, particularly the modulation of the neurotransmitter serotonin and (b) those that suppress ovulation. Psychotropic medication, such as selective serotonin reuptake inhibitors, probably acts by dampening the influence of sex steroids on the brain. Oral contraceptives, gonadotropin-releasing hormone agonists, danazol and estradiol all most likely function by ovulation suppression. The role of oophorectomy was also considered in this respect. Alternative therapies are also addressed, with, e.g. cognitive behavioural therapy, calcium supplements and Vitex agnus castus warranting further exploration.