Drugs in early clinical development for the treatment of female sexual dysfunction.

INTRODUCTION: There is growing recognition of female sexual dysfunction (FSD) as an important women's health concern. Despite an increased awareness of the pathophysiologic components to FSD, currently, there are no drugs approved for the most common sexual complaint in women-decreased sexual desire. In response to an overwhelming demand for therapy for FSD, several drugs are undergoing development and testing. AREAS COVERED: The aim of this paper is to provide the latest data on pharmacological treatments for FSD currently in Phase I and II clinical trials. These include topical alprostadil, bremelanotide (BMT), intranasal testosterone (TBS-2), intravaginal dehydroepiandrosterone (DHEA), sublingual testosterone with sildenafil, apomorphine (APO), bupropprion and trazodone. It should be noted that the definitions of FSD have recently been revised in the diagnostic and statistical manual for mental disorders (DSM) 5, with merging of hypoactive sexual desire disorder (HSDD) and female sexual arousal disorder (FSAD) into female sexual interest/arousal disorder (FSIAD). However, it is noted that the majority of clinical trials discussed in this paper use the DSM IV-R diagnoses of HSDD and FSAD. EXPERT OPINION: Medications in early phase trials show promise for the treatment of FSD. These therapies focus on treating many possible causes of FSD. Concerns over gender bias within the FDA need to be resolved given the need for new treatment options for FSD.

Polymorphisms of the androgen receptor gene and hormonal contraceptive induced provoked vestibulodynia.

AIM: Women who developed vestibulodynia (vulvar vestibulitis) while taking combined hormonal contraceptives (CHCs) and a control group of women were tested for polymorphisms of the gene coding for the androgen receptor (AR) that is located on the X chromosome. STUDY DESIGN: DNA from 30 women who developed vestibulodynia while taking CHCs and 17 control women were tested for the number of cytosine-adenine-guanine (CAG) trinucleotide repeats in the AR. In addition, serum-free testosterone was tested in both groups. RESULTS: The mean number of CAG repeats in the study group was significantly greater than the control group (22.05 ± 2.98 vs. 20.61 ± 2.19, respectively; P = 0.025). This significant difference persisted when analyzing the CAG repeats from the longer allele from each subject. Among those who were taking drospirenone-containing CHCs, the mean calculated free testosterone was 0.189 ± 0.115 ng/dL in the study group and 0.127 ± 0.054 ng/dL in the control group, all of whom were taking drospirenone-containing CHCs (P = 0.042). CONCLUSION: In the study cohort, women who developed vestibulodynia while taking CHCs are more likely to have longer CAG repeats in the AR than women who took the same type of CHC but did not develop vestibulodynia. We speculate that the risk of developing CHC-induced vestibulodynia may be due to lowered free testosterone combined with an inefficient AR that predisposes women to vestibular pain.

Influence of treatments on prognosis for vulvar lichen sclerosus: facts and controversies.

Lichen sclerosus (LS) is an inflammatory dermatosis with a predilection for the anogential skin. Vulvar LS can be a debilitating disease, causing pruritus and pain, and it carries the potential for atrophy, scarring, and significant functional impairment. Recently, many advances have been made regarding the etiology and natural history of the disease process; however, much debate still exists regarding the most advantageous medical and surgical management of this disorder. In an effort to provide a comprehensive review on current vulvar LS literature, the following three controversies will be discussed: (1) optimal disease treatment, (2) theories behind LS's oncogenicity and treatments for minimizing malignancy, and (3) the value of surgical treatment for LS. Ultra-potent topical corticosteroids (TCSs) are the first-line treatment for vulvar LS, while topical calcineurin inhibitors (TCIs) remain second-line agents for patients for whom TCS treatment resulted in incomplete resolution of symptoms or adverse events. Due to the relapsing nature of the disease, long-term maintenance therapy is often required. In addition, recent advances have contributed to the understanding of the association between LS and squamous cell carcinoma (SCC). While the exact mechanism responsible for LS-associated SCC is not known, immune dysregulation and inflammation may play an important role; therefore, successful treatment of LS should be directed towards alleviation of symptoms and reversal of the underlying histopathologic changes. Patients with LS-associated malignancy, as well as patients who need correction of functionally restrictive, scarring processes, can successfully undergo surgical intervention with tissue conservation.