Female sexual dysfunction: therapeutic options and experimental challenges

Abstract

Female sexual dysfunction (FSD) is a prevalent problem, afflicting approximately 40% of women and there are few treatment options. FSD is more typical as women age and is a progressive and widespread condition. Common symptoms associated with FSD include diminished vaginal lubrication, pain and discomfort upon intercourse, decreased sense of arousal and difficulty in achieving orgasm. Only a small percentage of women seek medical attention. In comparison to the overwhelming research and treatment for erectile dysfunction in males, specifically with the development of phosphodiesterase type 5 inhibitors, significantly less has been explored regarding FSD and treatment is primarily limited to psychological therapy. Several cardiovascular diseases have been linked with FSD including atherosclerosis, peripheral arterial disease and hypertension, all of which are also pathological conditions associated with aging and erectile dysfunction in men. Using animal models, we have expanded our understanding of FSD, however a tremendous amount is still to be learned in order to properly treat women suffering from FSD. The aim of this review is to provide the most current knowledge on FSD, advances in basic science addressing this dysfunction, and explore developing therapeutic options.

Fig. (1)

The psychogenic and hemodynamic events of the normal female sexual cycle. Psychosexual responses from arousal, orgasm and post orgasm frame approximate vaginal and labial pressures as well as clitoral volume. Increasing arousal that culminates in orgasm demonstrates increases in vaginal and labial pressures and filling of the clitoris. Data are compiled from several sources referenced in the text.

Fig. (2)

Representative trace showing changes in force (contraction and relaxation) of a female internal pudendal artery stimulated with increased concentrations of endothelin-1 (ET-1) and acetylcholine (ACh), respectively. The internal pudendal artery supplies blood to the clitoris and labia minora of the vagina. Relaxation of the internal pudendal artery is essential to achieve tumescence during sexual stimulation. A compromised state of relaxation in this artery may play a role in female sexual dysfunction.

Fig. (3)

Mechanism of smooth muscle relaxation and peripheral inhibition sites. Abbreviations: nitric oxide (NO), neuronal NO synthase (nNOS), endothelial NOS (eNOS), prostaglandin (PGE1), PGE1 receptor (EP2), guanosine triphosphate (GTP), guanylyl cyclase (GC), cyclic guanosine monophosphate (cGMP), phosphodiesterase type 5 (PDE5), adenosine triphosphate (ATP), cGMP-dependent protein kinase type I (cGKI), protein kinase A (PKA), cyclic adenosine monophosphate (cAMP), vasoactive intestinal peptide (VIP), VIP receptor (VIPR) and neutral endopeptidase (NEP).