Physical Activity and Female Sexual Dysfunction: A Lot Helps, But Not Too Much.

BACKGROUND: Research on the relationship between physical activity (PA) and female sexual dysfunction (FSD) is lacking. AIM: To investigate the clinical, psychological, and sexual correlates of PA in women with FSD. METHODS: A non-selected series of n = 322 pre- and post-menopausal patients consulting for FSD was retrospectively studied. Regular involvement in PA and its frequency (<1 hour/week: sedentary, 1-3 hours/week: active, 4-6 hours/week: very active, >6 hours/week: extremely active) were investigated with a specific question. OUTCOMES: FSDs, including HSDD (Hypoactive sexual desire disorder) and FGAD (Female genital arousal disorder), were diagnosed according to a structured and clinical interview. Participants underwent a physical examination and a clitoral Doppler ultrasound, and were asked to complete the Female Sexual Function Index, Female Sexual Distress Scale-Revised, Body Uneasiness Test, and Middlesex Hospital Questionnaire. RESULTS: At multivariate analysis, women engaging in PA (67.4%, n = 217) scored significantly higher in several Female Sexual Function Index domains - including desire, arousal and lubrication - and showed lower sexual distress and lower resistance of clitoral arteries, as compared to sedentary women. A significant, inverse association between PA and HSDD was observed. Mediation analysis demonstrated that the negative association between PA and HSDD was partly mediated by body image concerns (Body Uneasiness Test Global severity index), psychopathological symptoms (Middlesex Hospital Questionnaire total score) and sexual distress (Female Sexual Distress Scale-Revised score). These latter 2 factors also partly mediated the association between PA and a reduced risk of FGAD, whilst a lower BMI was a full mediator in the relationship between PA and FGAD. Finally, extreme PA was associated with significantly worse scores in several psychosexual parameters (i,e, sexual satisfaction and histrionic/hysterical symptoms), even compared to a sedentary lifestyle. CLINICAL IMPLICATIONS: Women consulting for FSD may gain benefits on desire, arousal, lubrication and sex-related distress from regular PA; however, physicians should remain alert to the downsides of excessive exercise. STRENGTHS & LIMITATIONS: The main strength lies in the novelty of the findings. The main limitations are the cross-sectional nature, the clinical setting, the small sample size of the different PA groups, and the use of self-reported instruments for the evaluation of PA. CONCLUSION: In women with FSD, PA was associated with better sexual function and clitoral vascularization, lower sexual distress and reduced odds of HSDD and FGAD; the benefits of PA on sexuality were mediated by both psychological and organic determinants; excessive PA was related with a poor overall sexual function and with a low sexual satisfaction. Maseroli E, Rastrelli G, Di Stasi V, et al. Physical Activity and Female Sexual Dysfunction: A Lot Helps, But Not Too Much. J Sex Med 2021;18:1217-1229.

SHBG as a Marker of NAFLD and Metabolic Impairments in Women Referred for Oligomenorrhea and/or Hirsutism and in Women With Sexual Dysfunction.

PCOS is one of the most common endocrine disorders and NAFLD is one of its most dangerous metabolic consequences. The diagnosis of NAFLD is not a practical task and the condition is at risk of being overlooked. The use of simpler but still reliable surrogate markers is necessary to identify women with a high likelihood of NAFLD. The aim of this study was to evaluate the clinical correlates of NAFLD Liver Fat Score (NAFLD-LFS) in women with oligomenorrhea and/or hirsutism. Furthermore, the study aimed to evaluate whether, among the hormonal parameters evaluated in such women, possible hallmarks of NAFLD may be identified. To this purpose, 66 women who attended our Outpatient Clinic for oligomenorrhea and/or hyperandrogenism were included in the study. In order to validate the results obtained in the first cohort, a second independent sample of 233 women evaluated for female sexual dysfunction (FSD) was analyzed. In cohort 1, NAFLD-LFS positively correlated with metabolic and inflammatory parameters. Among the hormone parameters, NAFLD-LFS showed no significant relationships with androgens but a significant negative correlation with SHBG (p<0.0001) that therefore appeared as a candidate hallmark for pathologic NAFLD-LFS. The ROC analysis showed a significant accuracy (81.1%, C.I.69.1-93.0, p <0.0001) for SHBG in identifying women with a pathological NAFLD-LFS. In particular, a SHBG 33.4 nmol/l was recognized as the best threshold, with a sensitivity of 73.3% and a specificity of 70.7%. In order to validate this SHBG as a marker of metabolic impairment possible related with the presence of NAFLD, we tested this threshold in cohort 2. FSD women with SHBG <33.4 nmol/l had worse metabolic parameters than women with SHBG ≥33.4 nmol/l and a significantly higher NAFLD-LFS even after adjusting for confounders (B=4.18 [2.05; 6.31], p=0.001). In conclusion, this study provides a new evidence in the diagnostic process of NAFLD, showing that the measurement of SHBG, which is routinely assessed in the workup of women referred for possible PCOS, could identify women at higher metabolic risk, thus detecting those who may deserve further targeted diagnostic assessment.

Insight on the Intracrinology of Menopause: Androgen Production within the Human Vagina.

In this study, we investigated steroidogenic gene mRNA expression in human vaginas and verified the ability of human vagina smooth muscle cells (hvSMCs) to synthesize androgens from upstream precursor dehydroepiandrosterone (DHEA). As a readout for androgen receptor (AR) activation, we evaluated the mRNA expression of various androgen-dependent markers. hvSMCs were isolated from vagina tissues of women undergoing surgery for benign gynecological diseases. In these cells, we evaluated mRNA expression of several steroidogenic enzymes and sex steroid receptors using real time reverse transcription-polymerase chain reaction. Androgen production was quantified with liquid chromatography tandem-mass spectrometry (LC-MS/MS). In vaginal tissues, AR mRNA was significantly less expressed than estrogen receptor α, whereas in hvSMCs, its mRNA expression was higher than progestin and both estrogen receptors. In hvSMCs and in vaginal tissue, when compared to ovaries, the mRNA expression of proandrogenic steroidogenic enzymes (HSD3ß1/ß2, HSD17ß3/ß5), along with 5α-reductase isoforms and sulfotransferase, resulted as being more abundant. In addition, enzymes involved in androgen inactivation were less expressed than in the ovaries. The LC-MS/MS analysis revealed that, in hvSMCs, short-term DHEA supplementation increased Δ4-androstenedione levels in spent medium, while increasing testosterone and DHT secretion after longer incubation. Finally, androgenic signaling activation was evaluated through AR-dependent marker mRNA expression, after DHEA and T stimulation. This study confirmed that the human vagina is an androgen-target organ with the ability to synthesize androgens, thus providing support for the use of androgens for local symptoms of genitourinary syndrome in menopause.

Nomegestrol acetate/17beta-estradiol does not negatively alter the vascular resistance of clitoral arteries: a prospective, exploratory study.

The effect of nomegestrol acetate/estradiol (NOMAC/E2) on clitoral and uterine vascularization has never been evaluated. We aimed to investigate, in women consulting for contraceptive needs, the possible changes in clitoral and uterine arteries hemodynamic parameters after 6 months treatment with NOMAC/E2 as compared with other hormonal contraceptives (HCs). In this observational, prospective pilot study, ten women were enrolled. Color Doppler ultrasound was performed on the clitoral and uterine arteries at baseline and after 6 months treatment with NOMAC/E2 (n = 5) or other HCs (n = 5). NOMAC/E2 did not exert any significant effect on clitoral vascular resistance expressed by the pulsatility index (PI); conversely, treatment with other HCs significantly increased this parameter (p = 0.04). The change in clitoral PI between the two groups retained a statistically significant difference even after adjusting for age. In the NOMAC/E2 group, at follow-up, uterine artery PI and acceleration were significantly reduced (p = 0.04), whereas no significant differences were observed in the HCs group; however, the change in uterine artery parameters did not differ significantly between the two groups. NOMAC/E2, differently from other COCs, does not negatively alter the vascular resistance of clitoral arteries and appears as a good contraceptive choice to protect both cardiovascular and sexual health.

Obesity and hormonal contraception: an overview and a clinician's practical guide.

BACKGROUND: The growing prevalence of obesity among the fertile female population poses a considerable problem to contraceptive providers. Obese women, who are more at risk for venous thromboembolism and cardiovascular events due to their condition, might be at an even higher risk of developing thromboembolic events when on medical contraception. Combined hormonal contraceptives might be less effective in obese women and may lead to unacceptable metabolic side effects for this population. In addition, the lack of safety data for weight loss drugs and the higher risk for complications during and after pregnancy require a close surveillance of the fertility status of obese patients. OBJECTIVE: The aim of this narrative review is to summarize the available medical contraceptive options and to give the readers a practical guidance for a wise contraceptive choice with regards to obesity. METHODS: A general literature review of peer-reviewed publications on the topic "obesity and contraception" was performed using the PubMed database. RESULTS: Nowadays, there are many useful tools that help clinicians in choosing among the wide range of therapeutic possibilities, such as the World Health Organization (WHO) Medical Eligibility Criteria for contraceptive use. Furthermore, the great diversity of hormonal contraceptive formulations (combined hormonal formulations; progestin-only methods) and active substances (different estrogens and progestins) allow physicians to tailor therapies to patients' clinical peculiarities. CONCLUSION: Long-acting reversible contraceptives [progestin-only implants, levonorgestrel-intra-uterine devices (IUDs) and copper IUDs] and progestin-only methods in general are excellent options for many categories of patients, including obese ones. LEVEL OF EVIDENCE: V, narrative review.

Sexual Health in Menopause.

Sexual function worsens with advancing menopause status. The most frequently reported symptoms include low sexual desire (40-55%), poor lubrication (25-30%) and dyspareunia (12-45%), one of the complications of genitourinary syndrome of menopause (GSM). Declining levels of sex steroids (estrogens and androgens) play a major role in the impairment of sexual response; however, psychological and relational changes related with aging and an increase in metabolic and cardiovascular comorbidities should also be taken into account. Although first-line therapeutic strategies for menopause-related sexual dysfunction aim at addressing modifiable factors, many hormonal and non-hormonal, local and systemic treatment options are currently available. Treatment should be individualized, taking into account the severity of symptoms, potential adverse effects and personal preferences.

Outcome of Medical and Psychosexual Interventions for Vaginismus: A Systematic Review and Meta-Analysis.

INTRODUCTION: Although vaginismus is a condition with a great impact on psychosexual well-being, the evidence on the efficacy of interventions is lacking. AIM: To review all information on vaginismus treatment, including data from randomized clinical trials (RCTs) and observational studies. METHODS: A systematic search was conducted of MEDLINE, EMBASE, PsycINFO, and ClinicalTrials.gov. 2 Independent meta-analyses of RCTs and observational studies were performed. For RCTs, only those having no treatment as the comparator were considered eligible. MAIN OUTCOME MEASURE: The primary outcome was the success rate (number of successes/total sample) in the completion of sexual intercourse. RESULTS: 43 Observational studies (n = 1,660) and 3 RCTs (n = 264) were included in the final analyses, respectively. In the meta-analysis of RCTs, the use of psychological interventions showed a trend toward a significantly better result vs waiting list control (OR 10.27 [95% CI 0.79-133.5], P = .075). The combination of the results obtained from the observational studies showed that treating vaginismus is associated with the completion of sexual penetrative intercourse in 79% of cases, independently of the therapy used (success rate 0.79 [0.74-0.83]). When only moderate- or strong-quality studies were considered, the success rate was 0.82 (0.73-0.89). As for the different definitions of vaginismus, studies with unconsummated marriage as the inclusion criterion showed the worst success rate (0.68). The origin of vaginismus (primary, secondary, or both), its duration, the mean age of the participants, the involvement of the partner in the intervention, or the geographic setting did not exert a significant effect on the outcome. Studies enrolling women with unconsummated marriage showed a significantly worse success rate. CLINICAL IMPLICATIONS: No approach is superior to the others in allowing the achievement of penetrative intercourse in women with vaginismus. STRENGTH & LIMITATIONS: Only studies specifically enrolling patients with vaginismus were selected, and analyses were performed on an intention-to-treat approach. The main limitations are the small number of trials in the meta-analysis of RCTs and the lack of a comparison group in the meta-analysis of observational studies, which cannot rule out a placebo effect. Due to the limited evidence available, great caution is required in the interpretation of results. Further well-designed trials, with more appropriate outcomes than penetrative sex, are required. CONCLUSION: The meta-analysis of RCTs documented a trend toward higher efficacy of active treatment vs controls, whereas the meta-analysis of observational studies indicated that women with vaginismus benefit from a range of treatments in almost 80% of cases. Maseroli E, Scavello I, Rastrelli G, et al. Outcome of Medical and Psychosexual Interventions for Vaginismus: A Systematic Review and Meta-Analysis. J Sex Med 2018;15:1752-1764.

Psychosexual Correlates of Unwanted Sexual Experiences in Women Consulting for Female Sexual Dysfunction According to Their Timing Across the Life Span.

BACKGROUND: Comparative data on the psychopathologic and sexual correlates of unwanted sexual experiences (USEs) occurring during childhood, adolescence, or adult life are lacking. AIM: To investigate the prevalence of USEs in a setting of female sexual dysfunction (FSD) and to examine whether they are associated with different psychosexual parameters depending on the timing of occurrence. METHODS: A consecutive series of 200 heterosexual women attending our clinic for FSD was consecutively recruited. MAIN OUTCOME MEASURE: Patients underwent a structured interview and completed the Female Sexual Function Index, the Middlesex Hospital Questionnaire, the Female Sexual Distress Scale-Revised, the Body Uneasiness Test, and the Childhood Experience of Care and Abuse questionnaire. USEs were classified as occurring in adult life (≥17), adolescence (<17 and ≥14), or childhood (<14 years). RESULTS: 47 women (23.5%) reported USEs, occurring in childhood, adolescence, and adult life in 38.3% (n = 18), 31.9% (n = 15), and 29.8% (n = 14) of cases, respectively. We observed an association between history of lifetime USEs and indexes of psychopathology, specifically diagnosis of psychiatric diseases, use of psychiatric medications, and anxiety symptoms (Middlesex Hospital Questionnaire free-floating anxiety score). USEs were associated with lower orgasm ability (Female Sexual Function Index orgasm domain), higher sexually related distress levels (Female Sexual Distress Scale-Revised total score), and higher body image concerns (Body Uneasiness Test) including depersonalization symptoms. Notably, women exposed to USEs in adolescence reported a stronger impairment of arousal, orgasm, and satisfaction domains and higher sexual distress when compared to women without a history of USEs or reporting USEs in childhood. Women exposed to USEs in childhood exhibited higher body image concerns and depersonalization symptoms when compared to those not reporting USEs. CLINICAL IMPLICATIONS: USEs should be investigated in women consulting for FSD because patients who had USEs may require unique strategies to optimize the diagnostic and therapeutic work-up of their sexual symptoms. STRENGTH & LIMITATIONS: Our main contribution is that we addressed the different impacts of USEs depending on their timing across the life span. However, the cross-sectional nature of the study does not allow determination of the cause-and-effect nature of the associations, and the selectivity of the sample (women consulting for FSD) limits the generalizability of the results. CONCLUSION: The negative outcomes of USEs vary according to their timing of occurrence: adolescence appears as the most sensitive temporal window for USEs to exert their deleterious effects on female sexuality, whereas childhood USEs are more tightly related to a severe body uneasiness in adult life. Maseroli M, Scavello I, Campone B, et al. Psychosexual Correlates of Unwanted Sexual Experiences in Women Consulting for Female Sexual Dysfunction According to Their Timing Across the Life Span. J Sex Med 2018;15:1739-1751.

Cardiometabolic Risk and Female Sexuality-Part I. Risk Factors and Potential Pathophysiological Underpinnings for Female Vasculogenic Sexual Dysfunction Syndromes.

INTRODUCTION: Erectile dysfunction is recognized as an opportunity for preventing cardiovascular (CV) events, and assessing the impairment of penile vascular flow by Doppler ultrasound is an important tool to ascertain CV risk. Conversely, the role of genital vascular impairment in the pathophysiology of female sexual dysfunction (FSD) remains contentious. AIM: To focus on the current scientific support for an association between CV risk factors and female sexual health in the 1st part of a 2-part review. METHODS: A thorough literature search of peer-reviewed publications on the associations between CV risk factors and FSD and their underlying mechanisms was performed using the PubMed database. MAIN OUTCOME MEASURES: We present a summary of the evidence from clinical studies and discuss the possible mechanisms providing the pathophysiologic bases of vasculogenic FSD syndromes. RESULTS: The peripheral sexual response in women is a vascular-dependent event, and evidence suggests that cardiometabolic-related perturbations in endothelial function can determine vascular insufficiency in female genital tissues. Although epidemiologic and observational studies demonstrate that the prevalence of FSD is higher in women with diabetes mellitus, a cause-effect relation between these clinical conditions cannot be assumed. Evidence on the effect of obesity, metabolic syndrome, and polycystic ovary syndrome on sexual function in women is controversial. Data on the associations of dyslipidemia and hypertension with FSD are limited. CONCLUSION: Common cardiometabolic alterations could affect vascular function in the female genital tract. Based on limited data, there is an association between CV risk factors and female sexual health in women; however, this association appears milder than in men. Maseroli E, Scavello I, Vignozzi L. Cardiometabolic Risk and Female Sexuality-Part I. Risk Factors and Potential Pathophysiological Underpinnings for Female Vasculogenic Sexual Dysfunction Syndromes. Sex Med Rev 2018;6:508-524.

Cardiometabolic Risk and Female Sexuality-Part II. Understanding (and Overcoming) Gender Differences: The Key Role of an Adequate Methodological Approach.

INTRODUCTION: Although basic science and clinical research indicate that the vascular physiopathology of male and female sexual dysfunction (FSD) is similar, to date the association between FSD and cardiovascular (CV) diseases has been only marginally explored. AIM: To discuss the potential reasons for differences in the role of CV diseases and risk factors in sexual function in women vs men in the 2nd part of a 2-part review. METHODS: A thorough literature search of peer-reviewed publications on the topic was performed using the PubMed database. MAIN OUTCOME MEASURES: We present a review of the main factors that could account for this gap: (i) actual physiologic discrepancies and (ii) factors related to the inadequacy of the methodologic approach used to investigate CV risk in patients with FSD. A summary of the available methods to assess female sexual response, focusing on genital vascularization, is reported. RESULTS: The microanatomy and biochemistry of the male and female peripheral arousal response are similar; in contrast, there are differences in the interplay between the metabolic profile and sex steroid milieu, in the relative weighting of cardiometabolic risk factors in the pathogenesis of CV disease, and their clinical presentation and management. CV diseases in women are under-recognized, leading to less aggressive treatment strategies and poorer outcomes. Moreover, evaluation of hemodynamic events that regulate the female sexual response has thus far been plagued by methodologic problems. CONCLUSION: To clarify whether sexuality can be a mirror for CV health in women, the female genital vascular district should be objectively assessed with standardized and validated methods. Studies designed to establish normative values and longitudinal intervention trials on the effect of the treatment of CV risk factors on FSD are urgently needed. Maseroli E, Scavello I, Vignozzi L. Cardiometabolic Risk and Female Sexuality-Part II. Understanding (and Overcoming) Gender Differences: The Key Role of an Adequate Methodological Approach. Sex Med Rev 2018;6:525-534.

Psychobiological Correlates of Vaginismus: An Exploratory Analysis.

BACKGROUND: Evidence concerning the determinants of vaginismus (V), in particular medical conditions, is inconclusive. AIM: To investigate, in a cohort of subjects consulting for female sexual dysfunction, whether there is a difference in medical and psychosocial parameters between women with V and women with other sexual complaints. METHODS: A series of 255 women attending our clinic for female sexual dysfunction was consecutively recruited. V was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Lifelong and acquired V cases were included. OUTCOMES: Patients underwent a structured interview and physical, gynecologic, laboratory, and clitoral ultrasound examinations; they completed the Female Sexual Function Index (FSFI), the Middlesex Hospital Questionnaire, the Female Sexual Distress Scale-Revised (FSDS), and the Body Uneasiness Test. RESULTS: V was diagnosed in 20 patients (7.8%). Women with V were significantly younger than the rest of the sample (P < .05). No differences were found for traditional risk factors such as a history of sexual abuse, relational parameters, or gynecologic diseases or for newly investigated parameters (ie, neurologic, hormonal, and metabolic alterations). Women with V showed significantly higher histrionic-hysterical symptoms and traits (as detected by MHQ-H score; P < .05) compared with subjects with other sexual complaints. When the scores of all MHQ subscales were simultaneously introduced in a logistic model, the association between V and MHQ-H score was confirmed (P = .013). Women with V also showed higher FSFI pain and FSDS total scores, even after adjusting for age (P < .05). In an age-adjusted model, FSDS total score increased as a function of the years of duration of V (P = .032) but not as a function of its severity. All observations were confirmed in a case-control study (ratio = 1:3). CLINICAL IMPLICATIONS: Our data demonstrate that some novel contributors of V should be investigated, namely histrionic-hysterical traits. This psychological comorbidity could offer valuable insights for intervention and managing complications. STRENGTHS AND LIMITATIONS: This is the first study to assess the role of many metabolic and hormonal parameters as potential determinants of V. The main limitation is its exploratory and cross-sectional nature; our data need to be confirmed in larger, more systematic analyses. CONCLUSION: V was associated with histrionic-hysterical traits, FSFI pain domain, and sex-related distress. A history of abuse, relational parameters, gynecologic diseases, and hormonal and metabolic alterations do not seem to play a role in the development of V. Maseroli E, Scavello I, Cipriani S, et al. Psychobiological Correlates of Vaginismus: An Exploratory Analysis. J Sex Med 2017;14:1392-1402.

Cardiometabolic Risk and Female Sexuality: Focus on Clitoral Vascular Resistance.

INTRODUCTION: The relation between sexual and cardiovascular health in women is not well defined. Clitoral color Doppler ultrasound (CDU) with assessment of the pulsatility index (PI), reflecting resistance to blood flow, has been proposed as an objective measurement of sexual functioning. AIM: To investigate associations between clitoral PI and cardiometabolic risk factors, sexual and intrapsychic parameters, and self-perception of body image. METHODS: Seventy-one adult heterosexual women in a stable relationship attending our clinic for sexual dysfunction were consecutively recruited. MAIN OUTCOME MEASURES: Patients underwent physical, laboratory, and clitoral color Doppler ultrasound examinations and completed the Female Sexual Function Index, the Middlesex Hospital Questionnaire, and the Body Uneasiness Test (BUT). RESULTS: Clitoral PI was positively correlated with body mass index (r = 0.441, P < .0001), waist circumference (r = 0.474, P < .0001), glycemia (r = 0.300, P = .029), insulin (r = 0.628, P = .002), homeostatic model assessment index (r = 0.605, P = .005), triglycerides (r = 0.340, P = .011), total cholesterol (r = 0.346, P = .010), and low-density lipoprotein cholesterol (r = 0.334, P = .016). All relations, with the exception of glycemia, retained statistical significance after adjusting for age, smoking habit, and years since menopause (P < .0001 for body mass index, waist circumference, and triglycerides; P < .05 for all other associations). Analysis of covariance, after adjusting for confounders, showed that women with obesity or metabolic syndrome (MetS) showed significantly higher PI values (obesity: F = 17.79, P = .001; MetS: F = 7.37, P = .019). In particular, a stepwise increase of PI was found as a function of increasing MetS components (ß = 0.434, P = .007). Clitoral PI was negatively associated with Female Sexual Function Index arousal (ß = -0.321, P = .014) and satisfaction (ß = -0.289, P = .026) scores and positively associated with Middlesex Hospital Questionnaire somatized anxiety symptoms, even after adjusting for age, smoking habit, years since menopause, and current use of psychiatric medication (ß = 0.354, P = .011). A positive association also was observed between PI and the BUT positive symptom distress index (ß = 0.322, P = .039) and BUT for dislike of the womb, genitals, and breast (ß = 0.538, P < .0001; ß = 0.642, P < .0001; ß = 0.549, P < .0001, respectively). After introducing waist circumference as another covariate, the associations between clitoral PI and the BUT positive symptom distress index and BUT dislike of the womb, genitals, and breast retained statistical significance (P = .038 for positive symptom distress index; P < .0001 for dislike of womb, genitals, and breast). CONCLUSION: Clitoral vascular resistance is positively associated with MetS (in particular insulin resistance), decreased sexual arousal, body image concerns, and increased somatized anxiety symptoms. Further studies are needed to establish whether treatment of metabolic abnormalities might improve clitoral color Doppler ultrasound indices and sexual outcomes.