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Try out PMC Labs and tell us what you think. Learn More. 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, ificantly 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.
Human sexual function is an essential component of life, both in species propagation as well as quality of life. Sexual dysfunction can lead to reduced quality of life and potentially procreative advancement. Male sexual dysfunction, especially erectile dysfunction, has been extensively studied and effective therapies are available for men with this disorder.
However, female sexual dysfunction FSD is more complicated and ificantly less is understood in comparison to male sexual dysfunction. Therefore, the present review focuses on therapies available or in development as well as challenges faced by investigators in the study of FSD. Other recent reviews articles may be useful for understanding additional aspects of FSD [ 1 — 3 ].
Sexual function from a complex neurovascular process that is controlled by Lady looking sex Camp Smith and hormonal inputs. Like any coordinated physiological response, multiple systems are involved in this function. In respect to proper vaginal and clitoral function, a sufficient blood supply is required for a satisfying sexual experience. Vaginal and labial data were derived from partial oxygen pressures detected at each tissue site [ 4 ] while magnetic resonance imaging of the clitoris measured changes in volume during neutral and stimulating visual imagery [ 5 ]. FSD is a multifaceted disorder, comprising anatomical, psychological, physiological, as well as social-interpersonal components.
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. Appreciating the uniqueness of each FSD facet is critical in our understanding and potential treatment of FSD in general terms. Female sexual arousal disorders FASD can be defined as a recurrent inability to attain, or maintain until completion, sexual activity.
The arousal response consists of vasocongestion in the pelvis, vaginal lubrication, and expansion and swelling of external genitals. Orgasmic disorders can be categorized with FASD and are described as the persistent or recurrent difficulty, delay in, or absence of, attaining orgasm following sufficient sexual stimulation and arousal that le to personal distress. Sexual pain disorders are another form of FSD and are diagnosed as followed: dyspareunia, the recurrent or persistent genital pain associated with sexual intercourse, vaginismus, the recurrent or persistent involuntary spasm of the musculature of the outer third of the vagina that interferes with vaginal penetration, and noncoital sexual pain disorder, the recurrent or persistent genital pain induced by noncoital sexual stimulation.
By comparison, the Massachusetts Male Aging Study found that However, FSD remains relatively understudied and therapeutic breakthroughs, such as phosphodiesterase type 5 PDE 5 inhibitors used for erectile dysfunction, have yet to be discovered.
Throughout society, sexual disorders for women are influenced by both health-related and psychosocial factors. Taken together, this dynamic is associated with impaired quality of life and interpersonal relationships [ 11 ]. ificant improvements in overall clinical care have allowed the management of quality of life complications and not just the treatment of life-threatening diseases.
Importantly, several studies have linked cardiovascular diseases with sexual dysfunction, in both females [ 12 ] and males [ 13 ]. Therefore, the treatment of FSD as purely a lifestyle disorder may severely underestimate the seriousness of the situation. Recently, Schwarz et al. Indeed, the prevalence of sexual dysfunction in women with chronic compensated heart failure suggests a reduction in quality of life. Compared to the extensive sexual function studies conducted in diabetic men [ 15 ], substantially less is known regarding diabetic women. However, recent studies have demonstrated that diabetic women experience increased incidences of sexual dysfunction [ 16 — 18 ], including reduced sex drive, little to no arousal, vaginal dryness, difficulty in achieving orgasm and overall diminished sexual satisfaction [ 16 ].
Despite these observations, correlation between FSD and diabetes is not without controversy. A report on the frequency of psychosexual difficulties from diabetic women found secondary sexual dysfunction was reported in These authors concluded that, in diabetic women, sexual dysfunction was prominently a psychogenic complication.
Therefore, a more comprehensive understanding of the etiology and treatment options of FSD is crucial for improving existing conditions seen in women, as well as preventative measures of future, more fatal, pathologies. Animal models have been used to investigate female sexual function and dysfunction over the past 20 years and several experimental approaches have been developed. Particular aspects of female sexual function, more specifically desire and peripheral arousal, are currently under investigation in Lady looking sex Camp Smith science laboratory settings.
Accurately modeling FSD is an experimental challenge. However, investigating comorbid diseases, such as diabetes, cardiovascular disease and depression models, allows end-point measurements involved in FSD to be examined. This section will describe techniques currently in use and the challenges that investigators face studying FSD. Sexual desire in humans can be described as the presence of desire for sexual activity. Desire in animal models can be assessed by monitoring particular appetitive behaviors that occur during copulation as well as from certain unconditioned copulatory determinants [ 20 ].
In female rats, increased dopamine release in the striatum and nucleus accumbens le to repetitive voluntary return by depressing an access lever to attain access to male rats [ 2122 ]. These authors also showed that cage pacing an animalistic sexual desire response was increased when the same central pathways were stimulated [ 2324 ]. Translating findings similar to these to the clinical setting has revealed that dopamine agonists discussed further in the following section indeed increase sexual desire in women and is a viable treatment option for women that suffer from HSDD.
Sexual arousal encompasses a variety of outputs, including vaginal blood flow, clitoral, labial and vestibular bulb engorgement [ 20 ]. These physiological responses are neuronally controlled, which affects the contractility of vascular smooth muscle cells throughout the genitals.
Pelvic nerve stimulation PNS is a common technique used to induce tumescence of erectile tissue. Intracavernous pressure and blood flow can be measured by inserting a probe into vaginal tissue and the corpus cavernosum, and als to a laser Doppler blood flow monitor and thus, following PNS, changes in vaginal and clitoral blood flow can be measured. Recently, Angulo and colleagues demonstrated that treatment with vardenafil, a PDE5 inhibitor, increased vaginal and clitoral blood flow following PNS, which was assessed by laser Doppler, in a FSD-rabbit model where Lady looking sex Camp Smith animals were treated with anti-depressants [ 25 ].
The use of the female New Zealand white rabbit has given tremendous insight into genital hemodynamic measurements. Additionally, Giuliano and coworkers demonstrated using a scanning laser Doppler system that rat vaginal blood flow, as well as contractions and temperature were increased following PNS [ 27 ]. Ex vivo investigation of clitoral and vaginal strips, as well as the vasculature that delivers blood to these end-organs, have revealed contractility and relaxation states of these tissues. By using wire myographs, we have begun to characterize the contractile properties of internal pudendal arteries as well as the clitoral arteries, the vasculature that feed blood to the clitoris and labia minora, in female rats [ 28 ].
Using this technique, we have measured alterations in contraction, relaxation, aling, and drug effectiveness in physiological and pathological conditions Fig. Other researchers have demonstrated that experimentally-induced diabetic rats have diminished adrenergic- cholinergic- and NANC-neurotransmitter mechanisms in the smooth muscle of the vagina compared to control [ 29 ]. As well, Myung and colleagues demonstrated that an overactive bladder model in female rabbits deteriorated clitoral engorgement, which was associated with greater force generation through increased calcium sensitization and subsequently decreased relaxation, via activation of endothelin-1 ET-1 and Rho-kinase system [ 30 ], which support our findings [ 28 ].
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 AChrespectively. 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. These basic science techniques have and continue to advance our understanding of FSD, however several experimental challenges still remain.
Due to Lady looking sex Camp Smith anatomical characteristics and limitations in structure, physiological and pharmacological aspects of the rat clitoris have not been thoroughly investigated. In contrast, clitoral function and characteristics have been studied in larger animal studies rabbits and dogshowever these species are limited in experimental de when compared to rat. The investigation of FSD is complicated by many factors. Experimentally, modeling FSD is challenging due to the multifaceted and varied inputs that define this disorder.
Therefore endpoint measurements such as clitoral and vaginal blood flow, internal pudendal artery compliance and nerve-stimulated increases in pressure assist in the quantification of animal responses.
Direct study of FSD in animal models has proven difficult and therefore the disorder has been investigated in the study of other comorbid conditions diabetes, hypertension, ect. This approach could complicate the study of FSD in that the researcher must interpret data in conjunction with an additional disease condition. However, this may be a more realistic approach due to the commonalities between FSD and some cardiovascular diseases.
Currently there are few pharmacological options available in the treatment of FSD. Historically, FSD patients were Lady looking sex Camp Smith through psychological therapy; however as we have come to understand the extensiveness of the disorder, more basic science research and clinical recognition have been developed to address the problem. Several pharmacological initiatives are in development aimed at increasing blood flow to the genitals, improving androgen deficiencies and enhancing central nervous system stimulation.
Table 1 summarizes the potential and current treatment options available for FSD. Increasing blood delivery to the genitals with the development of the first marked PDE5 inhibitor, sildenafil revolutionized the treatment of erectile dysfunction in men. See Fig. NO produced by the sexual stimuli passes through the plasma membrane of the smooth muscle cell and Lady looking sex Camp Smith to guanylyl cyclase GS and soluble GS sGS. Other recent reviews articles regarding NO aling may be useful for understanding additional aspects of this mechanism [ 3233 ].
Mechanism of smooth muscle relaxation and peripheral inhibition sites. Several PDE5 inhibitors sildenafil, vardenafil and tadalafil are available for the treatment of erectile dysfunction. Though success of PDE5 inhibitors in males with sexual dysfunction did stimulate interest in treating FSD, the same effectiveness of this drug class has not been found across genders. Early clinical trials conducted by questionnaires in women with HSDD and FSAD showed some promise, revealing that sildenafil improved the ability to achieve orgasm and state of arousal [ 3435 ]. In addition, Cavalcanti et al showed that sildenafil ificantly improved clitoral blood flow in postmenopausal women with orgasmic dysfunction, measured by color and pulse Doppler [ 36 ].
Conversely however, an additional study investigating a broad spectrum of sexual dysfunction in women did not report beneficial effects of the PDE5 inhibitor [ 37 ]. Inconsistent reports on the effects of sildenafil between male and females may be explained by the different definitions or states of arousal between the genders.
PDE5 inhibitors increase genital engorgement [ 35 ] and blood flow [ 36 ] and recently, expression of numerous PDE isoforms were found in the human clitoris, vagina, and labia minora [ 38 ]. Prostaglandins PG are found in virtually all tissues and organs. They are autocrine and paracrine lipid molecules, which are quickly metabolized, and participate in a variety of physiological events, including blood flow regulation. Specifically, the PG isoform PGE1 aling through its EP2 receptor causes smooth muscle relaxation in the vaginal, uterine, as well as penile smooth muscle [ 39 ].
Prostaglandins have been used in male sexual dysfunction, especially erectile dysfunction administered through penile injectionfor some time and have displayed positive outcomes for certain women with genital sexual arousal disorder, most likely through increasing vaginal secretion and arterial smooth muscle relaxation [ 40 ]. Administered topically, thereby not resulting in systemic side effects, application of alprostadil demonstrated positive responses in genital vasocongestion, vaginal erythema, and transudate volume; however these effects were not consistently superior to placebo effects [ 41 ].
In a recent randomized, double blind, placebo-controlled study, female patients pre- and post-menopausal with FSAD displayed an improved sexual arousal rate when topical alprostadil was applied prior to vaginal intercourse [ 42 ]. Although topical alprostadil is a potential new therapy for the treatment of FSAD, more conclusive from ongoing clinical studies are needed to further validate the use of topical alprostadil in the treatment of FSAD.
It is well established that the production of NO is essential in vascular relaxation to numerous stimuli. PDE5 inhibitors augment NO-initiated dilation by propagating the downstream mediator, cGMP, through the activation of guanylate cyclase. Pacher et al. Some NO-donor creams are available Sensua! NO-independent stimulators and activators of sGS, including YC-1, BAY and A, have shown the ability to improve erectile function in rodents and could be targeted towards the treatment of FSD as well [ 44 ].
In a 4-week, placebo-controlled study, women in the pre, peri or post menopausal state who reported lack of sexual desire exhibited statistically ificant increases in clitoral sensitivity, sexual satisfaction, increased frequency of sexual intercourse and decreased vaginal dryness, compared to women in the control group [ 4748 ]. The authors reported that the changes in sexual satisfaction and elevated state of desire were stronger in pre-menopausal and less in the post-menopausal group, potentially due to alterations in hormonal levels.
Vasoactive intestinal peptide VIP is a polypeptide hormone containing 28 amino acid residues and is produced in many areas of Lady looking sex Camp Smith human body. VIP has potent vasorelexant effects and has been suggested to contribute to vaginal blood flow control [ 4950 ]. Like many peptidic therapies, oral administration of VIP is complicated by low bioavailability and high rate of clearance. Therefore, an alternative approach using an inhibitor of neutral endopeptidase NEPthe primary enzyme responsible for the degradation of VIP, has been in development under the assumption that inhibition of NEP will lead to more VIP in the circulation, which can increase clitoral and vaginal blood flow when sexually stimulated [ 2 ].Lady looking sex Camp Smith
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Female Sexual Dysfunction: Therapeutic Options and Experimental Challenges