Jill M. Krapf

The role of testosterone in the management of hypoactive sexual desire disorder in postmenopausal women.

At least 16 million women over the age of 50 currently experience low sexual desire, with approximately 4 million women exhibiting hypoactive sexual desire disorder (HSDD). Although early research established that testosterone therapy improves sexual desire in postmenopausal women, safer and more efficacious administration routes were explored. Large randomized, double-blinded placebo-controlled studies demonstrate that transdermal testosterone improves sexual function and activity in postmenopausal women with HSDD. Large multi-center Phase III trials further confirm the positive effects of the testosterone patch in the treatment of HSDD. More recent studies are exploring the utility of testosterone gels. Based upon data from two recent clinical relevance studies, physicians can be reassured that postmenopausal women with HSDD report a meaningful benefit with testosterone therapy, and further, women will only continue therapy if they experience a meaningful benefit. Although most trials combined testosterone with estrogen/progesterone therapy, the recent APHRODITE trial examined testosterone alone, showing increased sexual desire with mild adverse events. Concerns regarding the long-term safety profile of transdermal testosterone must be addressed before the FDA will approve a testosterone product for women. Although some fear an increased risk of breast cancer with exogenous testosterone administration, recent studies support the idea that androgens can play a role in suppressing the proliferative effects of estrogen and progesterone. Long-term safety data is now being collected and analyzed and Phase III trials focusing on long-term risks are underway. In the meantime, transdermal testosterone appears to be a safe and effective therapy for postmenopausal women with HSDD [Swanson S, DeRogatis L, Snabes M, Simes S, Zborowski J. Treatment of HSDD in surgically menopausal women: a newly initiated Phase III, randomized, double-blind, placebo-controlled, multi-center study of the safety and efficacy of LibiGel. Presented at the Annual Meeting of the International Society for the Study of Womens Sexual Health, February 22-25, Orlando, FL; 2007].

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.

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.

Two Case Presentations of Profound Labial Edema as a Presenting Symptom of Hypermobility-Type Ehlers–Danlos Syndrome

INTRODUCTION Hypermobility-type Ehlers-Danlos syndrome (EDS), an often-missed diagnosis with the potential for serious sequelae, may have a variety of uncommon presentations, some of which may be gynecologic. AIM The aim of this case report is to present two cases of profound labial edema associated with intercourse as a presenting symptom of hypermobility-type EDS. METHODS A 25-year-old female presented with severe labia minora swelling and bladder pressure associated with intercourse, in addition to persistent genital arousal. History revealed easy bruising, joint pain, and family history of aneurysm. A 22-year-old female presented with intermittent profound labial swelling for 6 years, associated with sensitivity and pain with intercourse. The patient has a history of joint pain and easy bruising, as well a sister with joint hypermobility and unexplained lymphedema. The presenting symptom of profound labial edema led to the diagnosis of hypermobility-type EDS. RESULTS Patients with hypermobility syndrome exhibit an increased ratio of type III collagen to type I collagen, causing tissue laxity and venous insufficiency. Abnormal collagen may lead to gynecologic manifestations, including unexplained profound labial edema, pelvic organ prolapse in the absence of risk factors, and possibly persistent genital arousal. CONCLUSIONS This case report highlights the need for further research to determine incidence of labial edema in hypermobility-type EDS and to further elucidate a potential correlation between profound labial edema and collagen disorders.

A Sex-Specific Dose-response Curve for Testosterone: Could Excessive Testosterone Limit Sexual Interaction in Women?

Abstract Testosterone treatment increases sexual desire and well-being in women with hypoactive sexual desire disorder; however, many studies have shown only modest benefits limited to moderate doses. Unlike men, available data indicate women show a bell-shaped dose-response curve for testosterone, wherein a threshold dosage of testosterone leads to desirable sexual function effects, but exceeding this threshold results in a lack of further positive sexual effects or may have a negative impact. Emotional and physical side-effects of excess testosterone, including aggression and virilization, may counteract the modest benefits on sexual interaction, providing a possible explanation for a threshold dose of testosterone in women. In this commentary, we will review and critically analyze data supporting a curvilinear dose-response relationship between testosterone treatment and sexual activity in women with low libido, and also explore possible explanations for this observed relationship. Understanding optimal dosing of testosterone unique to women may bring us one step closer to overcoming regulatory barriers in treating female sexual dysfunction.

Curricular response to increase recall and transfer of anatomical knowledge into the obstetrics/gynecology clerkship.

Deficits in retention of anatomy knowledge from the preclinical years to clinical application on the wards have been well documented in the medical education literature. We developed and evaluated a web and laboratory‐based curriculum to address deficits in anatomy knowledge retention and to increase anatomy knowledge recall through repetition and application of clinical concepts during the obstetrics and gynecology (Ob/Gyn) core clinical clerkship. Using principles of adult learning and instructional design, a curriculum was designed consisting of (1) interactive, case‐based e‐modules reviewing clinically relevant anatomical topics and (2) a hands‐on laboratory session reinforcing the content of the e‐modules, with the practice of clinical techniques using anatomical cadaveric dissections. The curriculums effectiveness was evaluated by using multiple choice testing and comparing baseline and final test scores. For questions testing content directly covered in this curriculum, mean final scores increased by 14.3% (P < 0.001). In contrast, for questions not directly addressed in this curriculum, mean final scores did not increase significantly, only by 6.0% (P = 0.31). Questions related to the uterus showed the greatest gains in final scores (30.3% improvement, P = 0.002). A curriculum with web‐based preparatory material and a hands‐on gross anatomy laboratory session effectively addresses deficits in anatomy retention and improves anatomical knowledge recall for medical students on a clinical clerkship. In the future, the authors plan to conduct a multicenter study to further evaluate the ability of this curriculum to improve clinically relevant anatomical knowledge. Anat Sci Educ 9: 337–343.

Current and Emerging Treatment Options for Vulvovaginal Atrophy

Vulvovaginal atrophy in postmenopausal women is common and manifests in vaginal dryness, irritation, itching, dysuria, and dyspareunia. Treatment used to be limited to estrogen-containing regimens which pose safety concerns. Today, however, practitioners are becoming better equipped to offer a wider range of treatment options due to increased reassurance of safety for existing therapies and advances in novel treatment options. Novel options include selective estrogen receptor modulators (SERMs), tissue-selective estrogen complexes (TSECs), local androgens such as testosterone and dehydroepiandrosterone (DHEA), the peptide hormone oxytocin, as well as phytoestrogens such as genistein and daidzein found in soybeans. Nonhormonal, over-the-counter vaginal lubricants and moisturizers are additional treatment options, in particular, for women contraindicated to estrogen use.

A Resource and Cost Analysis on the Impact of Reduced Visits for Prenatal Care [29F]

INTRODUCTION: Prenatal care is resource intensive, marked by frequent provider visits. Several studies have demonstrated reduced prenatal visits show no difference of outcomes in low risk pregnancies, yet are subject to decreased patient satisfaction. Our objective was to perform a resource analysis of reduced visits supplemented by the use of digital tools during prenatal care for improved satisfaction. METHODS: As accurate data on resource consumption during prenatal care is lacking, we first gathered these data from interviews of over 100 clinicians representing a variety of practice settings (private practices, academic centers & large systems). We then studied an alternative prenatal schedule with reduced visits supplemented with mobile technology and home monitoring. Finally, we extrapolated the impact of visit reduction from an individual pregnancy to a large system. RESULTS: On average, outpatient prenatal care was

Family history repeats itself Pain and swelling triggered by sexual intercourse had a genetic basis

1,164.66. With a modified visit schedule, the cost for a low risk pregnancy is reduced to

Preventing Excessive Gestational Weight Gain by Using Connected Weight Scales Paired With Mobile Apps [22L]

665.52, leading to a cost savings of