Peter Leusink

Efficacy and Safety of Flibanserin for the Treatment of Hypoactive Sexual Desire Disorder in Women: A Systematic Review and Meta-analysis

IMPORTANCE In August 2015, the US Food and Drug Administration (FDA) approved flibanserin as a treatment for hypoactive sexual desire disorder (HSDD) in premenopausal women, despite concern about suboptimal risk-benefit trade-offs. OBJECTIVE To conduct a systematic review and meta-analysis of randomized clinical trials assessing efficacy and safety of flibanserin for the treatment of HSDD in women. DATA SOURCES Medical databases (among others, Embase, Medline, Psycinfo) and trial registries were searched from inception to June 17, 2015. Reference lists of retrieved studies were searched for additional publications. STUDY SELECTION Randomized clinical trials assessing treatment effects of flibanserin in premenopausal and postmenopausal women were eligible. No age, language, or date restrictions were applied. Abstract and full-text selection was done by 2 independent reviewers. DATA EXTRACTION AND SYNTHESIS Data were extracted by one reviewer and checked by a second reviewer. Results were pooled using 2 approaches depending on the blinding risk of bias. MAIN OUTCOMES AND MEASURES Primary efficacy outcomes included number of satisfying sexual events (SSEs), eDiary sexual desire, and Female Sexual Function Index (FSFI) desire. Safety outcomes included, among others, 4 common adverse events (AEs): dizziness, somnolence, nausea, and fatigue. RESULTS Five published and 3 unpublished studies including 5914 women were included. Pooled mean differences for SSE change from baseline were 0.49 (95% CI, 0.32-0.67) between 100-mg flibanserin and placebo, 1.63 (95% CI, 0.45-2.82) for eDiary desire, and 0.27 (95% CI, 0.17-0.38) for FSFI desire. The risk ratio for study discontinuation due to AEs was 2.19 (95% CI, 1.50-3.20). The risk ratio for dizziness was 4.00 (95% CI, 2.56-6.27) in flibanserin vs placebo, 3.97 (95% CI, 3.01-5.24) for somnolence, 2.35 (95% CI, 1.85-2.98) for nausea, and 1.64 (95% CI, 1.27-2.13) for fatigue. Womens mean global impression of improvement scores indicated minimal improvement to no change. CONCLUSIONS AND RELEVANCE Treatment with flibanserin, on average, resulted in one-half additional SSE per month while statistically and clinically significantly increasing the risk of dizziness, somnolence, nausea, and fatigue. Overall, the quality of the evidence was graded as very low. Before flibanserin can be recommended in guidelines and clinical practice, future studies should include women from diverse populations, particularly women with comorbidities, medication use, and surgical menopause.

Comorbidities Among Women With Vulvovaginal Complaints in Family Practice.

BACKGROUND The lifetime prevalence of women suffering from provoked vestibulodynia (PVD) is estimated to be approximately 15%. The etiology of PVD is not yet clear. Recent studies approach PVD as a chronic multifactorial sexual pain disorder. PVD is associated with pain syndromes, genital infections, and mental disorders, which are common diseases in family practice. PVD, however, is not included in the International Classification of Primary Care. Hence, the vulvovaginal symptoms, which could be suggestive of PVD, are likely to be missed. AIM To explore the relationship between specific vulvovaginal symptoms that could be suggestive of PVD (genital pain, painful intercourse, other symptoms/complaints related to the vagina/vulva), and related diseases such as pain syndromes, psychological symptom diagnoses, and genital infections in family practice. METHODS A retrospective analysis of all episodes from 1995 to 2008 in 784 women between 15 and 49 years were used to determine the posterior probability of a selected diagnosis in the presence of specific vulvovaginal symptoms suggestive of PVD expressed in an odds ratio. Selected comorbidities were pain syndromes (muscle pain, general weakness, irritable bowel syndrome [IBS]), psychological symptom diagnoses (anxiety, depression, insomnia), vulvovaginal candidiasis, and sexual and physical abuse. RESULTS Women with symptoms suggestive of PVD were 4 to 7 times more likely to be diagnosed with vulvovaginal candidiasis and 2 to 4 times more likely to be diagnosed with IBS. Some symptoms suggestive of PVD were 1 to 3 times more likely to be diagnosed with complaints of muscle pain, general weakness, insomnia, depressive disorder, and feeling anxious. CONCLUSION Data from daily family practice showed a clear relationship between symptoms suggestive of PVD and the diagnoses of vulvovaginal candidiasis and IBS in premenopausal women. Possibly, family doctors make a diagnosis of vulvovaginal candidiasis or IBS based only on clinical manifestations in many women in whom a diagnosis of PVD would be more appropriate.

Toward Personalized Sexual Medicine: Where is the Evidence?

Last year, this journal published three articles of the same research group on the potential efficacy of two different drug combinations (testosterone/phosphodiesterase inhibitor [T + PDE5i] and testosterone/buspirone [T + HT1ara]), in women with hypoactive sexual desire disorder [1–3]. T + PDE5i is hypothesized to activate excitatory mechanisms in the brain during sexual stimulation, and T + HT1ara is thought to block a hypothesized phasic increase in inhibitory serotonergic activity in the prefrontal cortex in response to negatively valenced sexual stimuli. The Dual Control model is used as a theoretical framework for this study [4]. A close reading of the three articles revealed a number of concerns that seriously question the validity of both the theoretical claims and the findings. We will address the following issues: (i) statistical analysis strategy; (ii) clinical significance of findings; (iii) placebo control; and (iv) conflicts of interest.

Is uncertain vulvovaginal candidiasis a marker of vulvodynia? A study in a Dutch general practice research database.

Background A recent Dutch study in general practice showed a clear relationship between the diagnosis of vulvovaginal candidiasis (VVC) and symptoms suggestive of provoked vulvodynia (PVD). PVD accounts for the largest group of vulvar pains, but is often not recognised by GPs. Aim To investigate whether diagnostic uncertainty about VVC in general practice could also point to the diagnosis of PVD, and whether and how this diagnostic uncertainty affects management. Design & setting An observational study in 2014 in Dutch general practices of the NIVEL Primary Care Database. Method Women with an uncertain diagnosis of VVC were distinguished from those with certain VVC based on the occurrence of recurrent episodes and persisting complaints, despite treatment. Factors known to be associated with PVD were hypothesised to be more prevalent in women with uncertain VVC. Data on symptom management by GPs were collected. Results In total 7066 women with VVC or uncertain VVC were included. Uncertain VVC was found to account for 28% of these patients. Compared to VVC, the group uncertain VVC included significantly more women with female genital symptoms, tiredness, irritable bowel syndrome (all P<0.001), feeling anxious, reduced sexual desire, depressive disorder, relationship problems, and micturition symptoms (all P<0.05). Compared to VVC, the group uncertain VVC included significantly higher mean numbers of telephone consultations (P<0.001), more referrals to gynaecology (P = 0.009), and higher mean numbers of prescriptions per patient (P<0.001). Conclusion This studys findings indicate that uncertain VVC could be a marker of PVD. GPs might reconsider their diagnostics and management when women present recurrent and persistent vulvovaginal complaints, especially if accompanied by dyspareunia, functional syndromes, micturition symptoms, and psychological conditions.

Incidentie van seksuele functieproblemen

SamenvattingKedde H, Donker G, Leusink P. Incidentie van seksuele functieproblemen. Huisarts Wet 2013;56(2):62-5.AchtergrondVan 2003 tot 2008 hebben de Continue Morbiditeits Registratie (CMR) Peilstations in 46 huisartsenpraktijken gegevens verzameld met betrekking tot de incidentie van seksuele functieproblemen.MethodeDe huisartsen registreerden alle patiënten die seksuele functieproblemen hadden en specificeerden deze op een aanvullende vragenlijst. Hierbij rapporteerden ze of het probleem samenhing met andere problemen, eventueel voor welke interventies ze hadden gekozen en of ze een afspraak hadden gemaakt voor een vervolgconsult en/of een verwijzing.ResultatenDe incidentie van seksuele functieproblemen bedraagt 95 per 100.000 patiënten – 132 per 100.000 mannen en 60 per 100.000 vrouwen. Bij mannen blijkt een erectieprobleem verreweg het meest gemelde probleem te zijn; bij vrouwen is dat dyspareunie (pijn bij het vrijen). Voor de periode 2003 tot 2008 hebben we geen verschillen gevonden in de incidentie van seksuele functieproblemen. Problemen met het seksueel verlangen hangen relatief vaak samen met psychische problemen, relatieproblemen bij mannen en medicijngebruik bij vrouwen. Seksuele pijnproblemen bij vrouwen gaan vaak samen met lichamelijke problemen. Bij vrouwen komen vaker meer seksuele functieproblemen tegelijkertijd voor dan bij mannen. Ook werden zij vaker dan mannen na één consult verwezen naar de tweedelijnszorg. In ongeveer de helft van alle eerste consulten maakte de huisarts een afspraak voor een vervolgconsult.ConclusieEr is geen duidelijk stijgende of dalende trend te zien in het diagnosticeren van seksuele functieproblemen in de huisartspraktijk. De aanwezigheid van comorbide problematiek duidt aan dat huisartsen geregeld te maken krijgen met complexe multifactoriële seksuele functieproblematiek. Een verwijzing naar een geregistreerd seksuoloog heeft dan de voorkeur. Gezien het geringe aantal verwijzingen naar de seksuoloog in dit onderzoek, is het raadzaam huisartsen beter te informeren over de verwijzingsmogelijkheden binnen het seksuologische veld. Hier ligt ook een taak voor de Huisarts Adviesgroep Seksuele Gezondheid (SeksHAG) van het NHG.

Facilitators and barriers in the diagnostic process of vulvovaginal complaints (vulvodynia) in general practice: a qualitative study

Abstract Background: The gap between the relatively high prevalence of provoked vulvodynia (PVD) in the general population and the low incidence in primary care can partly be explained by physicians’ lack of knowledge about the assessment and management of PVD. Objectives: To recognize barriers and facilitators of GPs in the diagnostic process of women presenting with recurrent vulvovaginal complaints. Methods: A qualitative focus group study in 17 Dutch GPs, five men and 12 women. An interview guide, based on the scientific literature and the expertise of the researchers, including a vignette of a patient, was used to direct the discussion between the GPs. The interviews were audiotaped and transcribed verbatim. A systematic text analysis of the transcripts was performed after data saturation was reached. Results: Analysis of the interviews generated three major themes: Identifying and discussing sexual complaints, importance of gender in professional experience, and coping with professional uncertainty. Within these themes, the reluctance regarding sexual complaints, male gender, negative emotional responses when faced with professional uncertainty, as well as lack of education were barriers to the diagnostic process and management of PVD. Female gender and understanding that patients can profit from enquiring about sexual health issues were found to be facilitating factors. Conclusions: To improve the care for women with PVD, attitude and skills of GPs regarding taking a sexual history and performing a vulvovaginal examination should be addressed, as well as GPs’ coping strategies regarding their professional uncertainty.

De rol van de huisarts bij onbedoelde zwangerschap

SamenvattingLeusink P, Folkeringa-de Wijs MA. De rol van de huisarts bij onbedoelde zwangerschap. Huisarts Wet 2017;60(6):298-301. In 2016 ontstond er een maatschappelijke discussie of en onder welke condities de huisarts de abortuspil zou mogen voorschrijven. In een ministerieel voorstel tot wijziging van de Wet afbreking zwangerschap (Waz) en een initiatiefnota van de SGP is een prominente rol weggelegd voor de huisarts. In deze klinische les beschrijven we de huidige rol van de huisarts bij ongewenste zwangerschap en de actuele stand van zaken rondom ‘de abortuspil’. Zodra de abortuspil door de huisarts mag worden voorgeschreven, komen we met een vervolg op deze klinische les.

Meer counseling in de NHG-Standaard Anticonceptie nodig

SamenvattingPicavet C, Leusink P. Meer counseling in de NHG-Standaard Anticonceptie nodig. Huisarts Wet 2017;60(8):393-5. De NHG-Standaard Anticonceptie wordt momenteel herzien. Er zijn niet veel nieuwe anticonceptiemethoden op de markt gekomen sinds de vorige herziening, maar er is wel nieuw onderzoek dat suggesties oplevert voor andere accenten in de standaard. Het gaat dan met name om de begeleiding van vrouwen in het eerste consult, zodat zij beter in staat zijn de kans op ongewenste zwangerschap te verkleinen. Het proefschrift The contraceptive cycle biedt een aantal nieuwe inzichten.

Dyspareunie bij oudere vrouwen (1)

SamenvattingDyspareunie bij oudere vrouwen is een belangrijk onderwerp met duidelijk huisartsgeneeskundige elementen.1 De auteurs slagen er echter in noch de NHG-Standaard De overgang, noch de juiste seksuologische concepten goed te integreren in hun louter urogynaecologische benadering van het probleem.

Seks, dat spreekt vanzelf?

SamenvattingLeusink P. Seks, dat spreekt vanzelf? Huisarts Wet 2015;58(11):582-5. Huisartsen praten weinig met hun patiënten over seksualiteit. In het algemeen doen ze ook weinig genitaal onderzoek en kennen ze hun seksueel actieve patiëntenpopulatie slecht, althans voorzover het gaat om mannen die seks hebben met mannen (MSM), prostituees, vrouwen die een abortus hebben ondergaan of patiënten die anticonceptie gebruiken. Bij diverse aan seksualiteit gerelateerde aandoeningen is het noodzakelijk seksualiteit proactief ter sprake te brengen of erop door te vragen om tot de juiste aanpak te komen. De reden waarom zo’n gesprek vaak toch moeizaam verloopt, is vooral gebrek aan scholing en training bij de huisarts. Seksuele gezondheid zou structureel meer aandacht kunnen krijgen binnen het huisartsgeneeskundig onderzoek en onderwijs.AbstractLeusink P. Talking about sex. Huisarts Wet 2015;58(11):582-5. General practitioners do not often talk with their patients about sexuality. In general, GPs perform few genital examinations and have little knowledge about their sexually active patient population, in terms of men who have sex with men, prostitutes, women who have had an abortion, and patients who use contraception. However, it is essential to actively ask about sexuality in order to adopt the appropriate treatment approach for a number of sex-related conditions. The reason why this type of consultation is often difficult in practice is the lack of training among GPs. More attention should be paid to sexual health in general practice medicine, research, and teaching.