Association between serotonin 2A receptor (HTR2A), serotonin transporter (SLC6A4) and brain-derived neurotrophic factor (BDNF) gene polymorphisms and citalopram/sertraline induced sexual dysfunction in MDD patients.

Sexual dysfunction (SD) is a troublesome adverse effect of selective serotonin reuptake inhibitors (SSRIs). A variety of mechanisms might be involved in the occurrence of SD but the exact mechanism is still not clear. Genetic variations among patients treated with SSRIs are strong determinants of intolerance and poor compliance. The present study aimed to determine the relationship between serotonin-2A receptor (HTR2A) gene -1438A/G and 102T/C polymorphisms, serotonin transporter gene (SLC6A4) 5-HTT-linked polymorphic region (5-HTTLPR) insertion/deletion variant and brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphisms and the occurrence of SD adverse effect in major depressive disorder patients treated with citalopram (CIT) or sertraline (SERT). The result from this investigation revealed that the -1438A/G and 102T/C polymorphisms appear to be associated with the SD induced by CIT. It was also demonstrated that patients receiving SERT, carrying T allele of HTR2A or L allele of 5-HTTLPR more likely to experience SD. Most important overall finding of the study is the combined effects of -1438A/G, 102T/C, and 5-HTTLPR polymorphisms. In a logistic regression model, the occurrence of SD increased with the number of risky alleles. As compared with subjects receiving SERT with few risky (≤2) alleles, those with had 5-6 alleles had an increased SD risk. After all, according to these findings, -1438A/G, 102T/C, and 5-HTTLPR polymorphisms could be considered as promising pharmacogenetic biomarkers in CIT/SERT treatment in major depressive disorder (MDD) patients to avoid the occurrence of SD.

Circular RNA Expression Profiles in Vaginal Epithelial Tissue of Women With Lubrication Disorders.

INTRODUCTION: Recently, circular RNA (circRNA) has been proved to occupy a vital pathological position in many diseases by acting as microRNAs sponges. However, the role of circRNA in female sexual dysfunction (FSD), especially in lubrication disorders (LDs), remains unclear. AIM: The aim of this study was to detect circRNA expression in LDs, analyzed target genes, and pathways regulated by the differently expressed circRNAs. METHODS: In this study, next-generation sequencing was first conducted to produce circRNA expression profiles of FSD groups and normal control groups. Furthermore, differences in expression of 6 randomly selected circRNAs were confirmed through real-time quantitative polymerase chain reaction. Kyoto Encyclopedia of Genes and Genomes biological pathway analysis and Gene Ontology showed that immune processes and infection could be involved in the development of FSDs. MAIN OUTCOME MEASURE: CircRNA expression in vaginal epithelial tissue obtained from women with LDs have been detected. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes biological pathway analysis, and circRNA-microRNA interaction predictions were investigated. RESULTS: Totally, 7,746 circRNAs of vaginal epithelial tissue from women of 2 groups were sequenced. Preliminary judgment revealed that there were 73 circRNAs that have significant differential expression, including 53 downregulated circRNAs and 20 upregulated circRNAs. Research results also displayed that the majority of circRNAs has multiple binding sites of microRNAs, including miR-137, which has been reported to be linked to FSD. CLINICAL IMPLICATIONS: We predicted 10 circRNAs paired with hsa-miR-137-5p, but the mechanism of circRNA involvement in disease development remains to be further explored. STRENGTHS & LIMITATIONS: For the first time, the research disclosed the potential pathogenesis of LDs. However, we only analyzed the expression profile of circRNA in FSD, no specific mechanism was further confirmed or proposed. We still have a preliminary understanding, and more research is needed to explore the target of FSD treatment. CONCLUSION: The results suggest that circRNAs have different expression in the FSD groups and play a vital part in the occurrence and development of FSD. Zhang J, Xia H, Zhang A, et al. Circular RNA Expression Profiles in Vaginal Epithelial Tissue of Women With Lubrication Disorders. J Sex Med 2019;16:1696-1707.

Risk factors for sexual dysfunction in BRCA mutation carriers after risk-reducing salpingo-oophorectomy.

OBJECTIVE: The aim of the study was to identify risk factors for sexual dysfunction in BRCA mutation carriers who have undergone risk-reducing salpingo-oophorectomy (RRSO). METHODS: A cross-sectional study was performed. BRCA1/2 mutation carriers with and without RRSO were surveyed to determine sexual function (Female Sex Function Index [FSFI]), demographics, medical history, sleep quality, depression, and anxiety scores. Characteristics of patients with the lowest quartile of FSFI scores (<14 ±â€Š8.8) were analyzed to identify risk factors for the most severe phenotype. RESULTS: In the 804 women surveyed, 764 underwent RRSO. Of the 529 (69%) carriers with completed FSFI questionnaires in the RRSO cohort, sexual dysfunction was reported in 77.3%. Poor sleep (P = 0.002), hot flashes (P = 0.002), lack of current systemic hormone therapy (HT) use (P = 0.002), depression (P < 0.001), and anxiety (P = 0.001) were associated with sexual dysfunction. In adjusted analyses, depression (adjusted odds ratio [aOR] 2.4, 95% CI, 1.4-4.1) and hot flashes (aOR 1.9, 95% CI, 1.2-3.0) remained significantly associated with sexual dysfunction. Depression was also a significant risk factor for the most severe degree of sexual dysfunction (OR 2.1, 95% CI, 1.3-3.5) and had the greatest impact on Arousal and Satisfaction domain scores of the FSFI. Current systemic HT use seemed to decrease the risk for sexual dysfunction (aOR 0.6, 95% CI, 0.4-1.0). CONCLUSIONS: Sexual dysfunction is highly prevalent in BRCA mutation carriers after RRSO. Depression seems to be a significant risk factor for sexual dysfunction in this patient population and may be under-recognized and undertreated. Patient and provider education on sexual side effects after surgery and risk factors for sexual dysfunction is necessary to decrease postoperative sexual distress. HT may be associated with improved sexual function after surgery.

Differential DNA Methylation in Monozygotic Twins Discordant for Female Sexual Functioning.

BACKGROUND: Research has repeatedly suggested genetic and environmental factors in the etiology underlying female sexual dysfunction (FSD). Because sexual functioning is a highly variable trait, epigenetics could provide a promising approach to tackle the origins of FSD and consequently offer a step-change in our understanding of these problems. AIM: To identify differentially methylated CpG positions for sexual functioning in a sample of monozygotic twin pairs discordant for sexual functioning. METHODS: The sample consisted of 33 trait-discordant monozygotic twin pairs (mean age = 54.1 years, SD = 9.05) from the Twins UK Registry. Phenotypic data on sexual desire, arousal, lubrication, orgasm, satisfaction, and pain were collected using the Female Sexual Function Index-Lifelong (FSFI-LL). The Illumina Infinium HumanMethylation 450 DNA BeadChip was used for epigenome-wide analyses of DNA methylation in whole-blood samples. OUTCOMES: Comparison of DNA methylation patterns associated with the FSFI-LL total score and its six subdomains. RESULTS: Two differentially methylated CpG positions (cg09580409 and cg14734994) reaching experiment-wide statistical significance were found for overall sexual functioning, mapping to MGC45800 and the threonine synthase-like 2 gene (THNSL2), respectively. Furthermore, potential biologically relevant candidates for sexual desire (CUB and zona pellucida-like domains 1, CUZD1) and satisfaction (solute carrier family 6 member 19, SLC6A19) were identified. CLINICAL TRANSLATION: THNSL2 and SLC6A19, which have been linked to weight and adiposity, might represent novel candidates for sexual problems in women. STRENGTHS AND LIMITATIONS: This is the first study to investigate epigenetic mechanisms underlying FSD. The study used a relative small sample of monozygotic female twins. The cutoff to determine discordance in sexual problems was chosen based on a 10% FSFI score difference. Therefore, the results have to be interpreted with caution and need replication in larger clinical samples. CONCLUSION: Understanding how genes and environment interact to influence our sexuality might inform clinical practice and lead to new treatments for women experiencing FSD. Burri A, Leupin M, Spector T, Marinova Z. Differential DNA Methylation in Monozygotic Twins Discordant for Female Sexual Functioning. J Sex Med 2017;14:1357-1364.

Female Sexual Dysfunction in Presymptomatic Mutation Carriers and Patients with Huntington's Disease.

BACKGROUND: Although in Huntington's disease (HD) movement, cognition, and personality are most significantly affected, autonomic dysfunction should not be neglected. In women with HD sexual dysfunction has not been adequately studied yet. OBJECTIVE: To report sexual dysfunction in a systematically studied cohort of female HD patients and compare it with controls of a similar age. METHODS: In female HD patients and presymptomatic HD mutation carriers, we compared the Female Sexual Function Index (FSFI) questionnaire, neurologic assessment using the Unified Huntington's Disease Rating Scale (UHDRS) and the Total Functional Capacity (TFC). RESULTS: Of 44 female HD patients and 9 presymptomatic HD mutation carriers, 30 HD patients and 8 HD mutation carriers responded our invitation to complete FFSI questionnaire. Finally, 23 HD women with a partner were compared to 47 controls with a partner. HD patients had more problems with sexual arousal, lubrication, orgasm and sexual satisfaction. By contrast, we found no difference in sexual desire and pain. Sexual dysfunction progressed in parallel with the decline in the TFC; severe sexual dysfunction occurred with TFC <7/13. CONCLUSIONS: Our study demonstrated a significant impact of HD on female sexual function that progressed with patients' functional decline and impaired patients' quality of life. Sexual dysfunction may be caused by progression of the disease itself, side effects of medication, and comorbidities like depression or dementia.

Association of brain-derived neurotrophic factor valine to methionine polymorphism with sexual dysfunction following selective serotonin reuptake inhibitor treatment in female patients with major depressive disorder.

INTRODUCTION: The occurrence of female sexual dysfunction (FSD) in patients with major depressive disorder (MDD) receiving selective serotonin reuptake inhibitors (SSRIs) treatment gives negative impacts on patients' quality of life and causes treatment discontinuation. We aimed to investigate whether genetic polymorphism of identified candidate gene is associated with FSD in our study population. METHODS: This is a cross-sectional study. A total of 95 female patients with MDD who met the criteria of the study were recruited and were specifically assessed on the sexual function by trained psychiatrists. Patients' DNA was genotyped for BDNF Val66Met polymorphism using real-time polymerase chain reaction. RESULTS: The prevalence of FSD in this study is 31.6%. In the FSD group, patients with problematic marriage were significantly more frequent compared with patients who did not have problematic marriage (P = 0.009). Significant association was detected in the lubrication domain with BDNF Val66Met polymorphism (P = 0.030) using additive genetic model, with even stronger association when using the recessive model (P = 0.013). DISCUSSION: This study suggested that there was no significant association between BDNF Val66Met with FSD. However, this polymorphism is significantly associated with lubrication disorder in patients treated with SSRIs.

Neurobiological Basis of Hypersexuality.

Until now, hypersexuality has not found entry into the common diagnostic classification systems. However it is a frequently discussed phenomenon consisting of excessive sexual appetite that is maladaptive for the individual. Initial studies investigated the neurobiological underpinnings of hypersexuality, but current literature is still insufficient to draw unequivocal conclusions. In the present review, we summarize and discuss findings from various perspectives: neuroimaging and lesion studies, studies on other neurological disorders that are sometimes accompanied by hypersexuality, neuropharmacological evidence, genetic as well as animal studies. Taken together, the evidence seems to imply that alterations in the frontal lobe, amygdala, hippocampus, hypothalamus, septum, and brain regions that process reward play a prominent role in the emergence of hypersexuality. Genetic studies and neuropharmacological treatment approaches point at an involvement of the dopaminergic system.

[Chinese herbal medicine enhances sexual function and c-Fos/nNOS expression in the nucleus accumbens of orchidectomized rats].

RESULTS: There was a decrease in accessory genital organ weight, plasma testosterone, and sexual behavior, as well as a low number of c-Fos-positive cells and a large nNOS-positive cell area in orchidectomized rats. Administration of the herbal medicine increased accessory genital organ weight, testosterone level, mating behavior, and c-Fos-positive cell number, while it decreased the nNOS-positive cell area in orchidectomized rats. CONCLUSION: An increase of plasma testosterone after administration of "kidney-nourishing" herbal medicine might contribute to the elevated sexual function and activity in orchidectomized rats. In addition, a central nervous system mechanism, such as the functional alteration of NAc, might be involved. Abstract OBJECTIVE: To determine whether the central nervous system is involved in the effect of Chinese herbal medicine on sexual function recovery in orchidectomized rats. METHODS: Orchidectomized rats were administered intragastrically with a decoction of "kidney-nourishing" Chinese herbal medicine once per day for 28 days. Accessory genital organ weight, plasma testosterone, and mating behavior were investigated. The expression of c-Fos and neuronal nitric oxide synthase (nNOS) in neuronal cells in the nucleus accumbens (NAc) was analyzed by immunohistochemistry.

Male sexual function in presymptomatic gene carriers and patients with Huntington's disease.

AIMS: To report sexual dysfunction in a systematically studied cohort of men with Huntington's disease (HD), and compare them with control men of a similar age. METHODS: In men with HD and asymptomatic HD gene carriers, the male sexual dysfunction questionnaire (International Index of Erectile Function--IIEF, covering erectile and orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction), neurologic assessment using the Unified Huntington's Disease Rating Scale (UHDRS) and the Total Functional Capacity (TFC) Score were utilized. RESULTS: Responses were obtained from 23 HD patients and 2 HD gene carriers. HD patients reported more problems with erection, intercourse satisfaction and overall satisfaction (p<0.05) compared to 41 controls. HD patients generally reported reduced sexual desire and performance. Sexual dysfunction progressed in parallel with patients' decline in motor (UHDRS) and TFC, but was not related to patients' age and duration of disease. CONCLUSIONS: Our study demonstrated a significant impact of HD on male sexual function that progressed in parallel with motor and total patient (TFC) dysfunction. Physicians helping HD patients should also consider this largely neglected aspect of the disease.

Reduced melanocortin production causes sexual dysfunction in male mice with POMC neuronal insulin and leptin insensitivity.

Proopiomelanocortin (POMC)-derived peptides like α-melanocyte-stimulating hormone (MSH) substantially improve hepatic insulin sensitivity and regulate energy expenditure. Melanocortinergic agents are also powerful inducers of sexual arousal that are being investigated for a possible therapeutic role in erectile dysfunction. It is currently unclear whether reduced melanocortin (MC) activity may contribute to the sexual dysfunction accompanying obesity and type 2 diabetes. Male rodents with leptin and insulin resistance targeted to POMC neurons (leptin receptor [LepR]/insulin receptor [IR]POMC mice) exhibit obesity, hyperinsulinemia, hyperglycemia, and systemic insulin resistance. In this study, we demonstrate that LepR/IRPOMC males are also subfertile due to dramatic alterations in sexual behavior. Remarkably, these reproductive changes are accompanied by decreased α-MSH production not present when a single receptor type is deleted. Unexpectedly, behavioral sensitivity to α-MSH and MC receptor expression are also reduced in LepR/IRPOMC males, a potential adaptation of the MC system to altered α-MSH production. Together, these results suggest that concurrent insulin and leptin resistance in POMC neurons in individuals with obesity or type 2 diabetes can reduce endogenous α-MSH levels and impair sexual function.

Gene expression profile of the neonatal female mouse brain after administration of testosterone propionate.

INTRODUCTION: Clinical care decisions for peripubertal adolescents with gender dysphoria (GD) should be made carefully. Furthermore, the identification of biomarkers is very important for rapid and accurate diagnosis of GD in young people. AIM: The aim of this study was to investigate gene expression profiles during masculinization of the neonatal female mouse brain by testosterone and to identify biomarkers related to GD. METHODS: Microarray analysis was performed using RNAs extracted from the brains of neonatal mice treated by intraperitoneal injection of testosterone propionate during the sexual determination period. Sequence motif enrichment analysis for sex hormone receptor responsive elements was performed for the flanking regions of genes that showed significant expression changes following administration of testosterone propionate. MAIN OUTCOME MEASURES: We revealed a gene set with marked changes in expression during brain masculinization of neonatal female mice following administration of testosterone propionate. RESULTS: We identified 334 genes that showed differential expression in the masculinized neonatal female brain after testosterone propionate treatment. Interestingly, most of these genes are not reported to be expressed in a sexually dimorphic manner. Moreover, sequence motif enrichment analysis suggested that masculinization of the neonatal female brain by testosterone was controlled more by estrogen receptors than androgen receptors. CONCLUSIONS: Differences in genes that are expressed differentially following administration of testosterone injection from known sexually dimorphic genes suggest that many GD-related genes are upregulated during female brain masculinization. The gene set identified in this study provides a basis to better understand the mechanisms of GD and delineate its associated biomarkers.

Androgen receptor gene CAG repeat polymorphism independently influences recovery of male sexual function after testosterone replacement therapy in postsurgical hypogonadotropic hypogonadism.

INTRODUCTION: Few and contradictory studies have evaluated the possible influence of androgen receptor (AR) gene CAG repeat polymorphism on male sexual function. AIM: In this study we evaluated the role of AR gene CAG repeat polymorphism in the recovery of sexual function after testosterone replacement therapy (TRT) in men affected by postsurgical hypogonadotropic hypogonadism, a condition which is often associated with hypopituitarism and in which the sexual benefits of TRT must be distinguished from those of pituitary-function replacement therapies. METHODS: Fifteen men affected by postsurgical hypogonadotropic hypogonadism were retrospectively assessed before and after TRT. MAIN OUTCOME MEASURES: Main outcome measures included sexual parameters as assessed by the International Index of Erectile Function questionnaire, levels of pituitary dependent hormones (total testosterone, free T3, free T4, cortisol, insulin-like growth factor-1 [IGF-1], prolactin), and results of genetic analysis (AR gene CAG repeat number). RESULTS: Plasma concentrations of free T3, free T4, cortisol, and prolactin did not vary significantly between the two phases, while testosterone and IGF-1 increased significantly after TRT. A significant improvement in all sexual parameters studied was found. The number of CAG triplets was negatively and significantly correlated with changes in all the sexual parameters, while opposite correlations were found between changes in sexual parameters and changes in testosterone levels; no correlation of change in IGF1 with change in sexual parameters was reported. On multiple linear regression analysis, after correction for changes in testosterone, nearly all the associations between the number of CAG triplets and changes in sexual parameters were confirmed. CONCLUSIONS: Shorter length AR gene CAG repeat number is associated with the recovery of sexual function after TRT in postsurgical male hypogonadotropic hypogonadism, independently of the effects of concomitant pituitary-replacement therapies.

Female sexual dysfunction in patients with major depressive disorder (MDD) treated with selective serotonin reuptake inhibitor (SSRI) and its association with serotonin 2A-1438 G/A single nucleotide polymorphisms.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) are known for their sexual side effects. Different SSRIs may affect different areas of sexual function at different rates. AIMS: The study aimed to determine the prevalence of female sexual dysfunction (FSD), its clinical correlates, and association with 5HT2A (rs6311) single nucleotide polymorphisms (SNPs) in patients with major depressive disorder (MDD) who were on SSRI therapy. METHODS: This was a cross-sectional study on 95 female outpatients with MDD treated with SSRI. The patients were in remission as determined by Montgomery-Asberg Depression Rating Scale. Genomic DNA was isolated from buccal swabs and samples were processed using a real time polymerase chain reaction. MAIN OUTCOME MEASURES: The presence or absence of FSD as measured by the Malay Version of Female Sexual Function Index and 5HT2A-1438 G/A (rs6311) SNP. RESULTS: The overall prevalence of FSD was 32.6%. After controlling for age, number of children, education level, total monthly income, SSRI types, and SSRI dosing, being employed significantly enhanced FSD by 4.5 times (odds ratio [OR] = 4.51; 95% confidence interval [CI] 1.00, 20.30; P = 0.05). Those having marital problems were 6.7 times more likely to have FSD (OR = 6.67; 95% CI 1.57, 28.34). 5HT2A-1438 G/A (rs6311) SNP was not significantly associated with FSD. CONCLUSION: There was no significant association between FSD and the 5HT2A (rs6311) SNP in patients with MDD on SSRI therapy. Employment status and marital state were significantly associated with FSD among these patients.

Trastornos del desarrollo sexual / Disorders of sex development

Antecedentes. Los trastornos del desarrollo sexual (TDS), que tienen la posibilidad de poner en riesgo vital las emergencias endocrinológicas del recién nacido, precisan un cuidadoso enfoque multidisciplinar. Objetivos. El objetivo de nuestro estudio es consolidar la propuesta de clasificación, evaluación y tratamiento de los TDS. Materiales y métodos. Se revisaron las literaturas relativas a TDS, a fin de hallar el mejor enfoque para esta enfermedad. Resultados. Se precisan la historia clínica detallada, la exploración física sistémica del paciente, el laboratorio concreto y las evaluaciones de imágenes para tratar urgentemente las anormalidades con riesgo vital y la asignación de género. Conclusión. Deberá asignarse el género dependiendo del diagnóstico definitivo, el potencial de fertilidad, el aspecto de los genitales, las opciones quirúrgicas y la opinión de los padres(AU)

Background. Disorders of sex development (DSD), which has the possibility of the risk of life-threatening endocrinologic emergencies of the newborn, require a careful multidisciplinary approach. Objectives. The aim of our study is to consolidate the proposed classification, evaluation and management of DSD. Materials and methods. The literatures related with DSD were reviewed to find the best approach for this disease. Results. The detailed history, systemic physical examination of the patient, particular laboratory and imagine evaluations are needed for the urgent treatment of life-threatening abnormalities and the gender assignment. Conclusion. The gender should be assigned depending on the definitive diagnosis, fertility potential, genital appearance, surgical options, and the parents’ opinion(AU)

Pharmacogenomics and sexuality: a vision.

Female sexual dysfunction (FSD) is multidimensional with a complex interplay of biopsychosocial factors modulating the clinical expression of sexual symptoms and associated distress. During the entire reproductive lifespan, intra- and interpersonal experiences shape human neuroendocrine and neurovascular sexual pathways. These are dependent on genetic and epigenetic mechanisms, including acquired medical conditions. Understanding the genetic basis of FSD can help to determine clinical phenotypes of women and therefore postulate the most effective intervention according to biological, psychological or environmental determinants. However, there is a paucity of studies demonstrating a genetic contribution to FSD and a diverse modulation of innate and acquired factors on discrete domains of sexual response and distress. This is evident from menarche to menopause. Pharmacogenomics is still in its infancy in the field of sexual medicine and most data regarding genetic polymorphisms of drug targets associated with susceptibility to sexual dysfunction have been obtained in males. Pharmacogenomics may be the future of medical practice in women with FSD and may guide an individualized approach by predicting both therapeutic effects at varying dosages of hormonal and non-hormonal agents, and disadvantageous side-effects and drug interactions.

A discordant monozygotic twin approach to testing environmental influences on sexual dysfunction in women.

The present study explored the causal role played by putative environmental factors on variation in female sexual dysfunction (FSD) by investigating FSD discordant monozygotic (MZ) twins, which permits a control over genetic confounders. In a population-based sample of female twins aged 25-69 years (M = 55 years), MZ twins discordant for recent and lifelong FSD were selected. Sample sizes varied depending on the specific sexual problem (N = 33-90 pairs). The Female Sexual Function Index (FSFI) score was used to discriminate cases from controls. Once genetic factors were controlled for, relationship satisfaction emerged as the strongest independent predictor for recent and lifelong FSD, being associated with FSFI dimensions measuring desire, arousal, and lubrication problems. The association with orgasm problems was especially strong (OR 7.1, 95% CI: 1.9-25.3) as was the association with sexual dissatisfaction (OR 5.1, 95% CI: 2.1-12.1). Furthermore, obsessive-compulsive symptomatology was weakly associated with desire problems (OR 1.5, 95% CI: 1.4-1.8) and anxiety-sensitivity with orgasm problems (OR 1.1, 95% CI: 0.9-1.3). Negligible effects were found for personality factors and small effects for self-reported abusive experiences. These data indicate, for the first time, that in women at identical genetic risk, relationship factors play a key role in the development of sexual problems. These findings require replication in prospective designs which can provide additional powerful tests of the direction of causality between interpersonal factors and later sexual dysfunction.

Bringing sex research into the 21st century: genetic and epigenetic approaches on female sexual function.

Behavioral genetic evidence offers a useful way to disentangle some of the multifactorial etiological pathways toward the now clearly multidimensional construct of female sexual dysfunction (FSD) and has already shown its potential in providing a better understanding of the heterogeneous factors underlying FSD. Understanding the genetic basis and therefore physiologic key mechanisms of sexual function and dysfunction has the potential for improved treatments (i.e., the development of new medication) and ultimately prevention. However, genetic epidemiologic research into FSD is scarce and highlights the need for more in-depth exploration using larger samples and more accurate phenotypes. Knowledge gained from genetic studies also highlights the importance of environmental factors and gene-environment interactions in disease development and maintenance. Exploration of DNA epigenetic patterns that regulate gene expression profiles could therefore provide the missing link between epigenomic state and FSD, and as such may offer a new biological framework for the multifactorial pathoetiology underlying FSD.