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Impaired Sexual Function in Young Women With PCOS: The Detrimental Effect of Anovulation

Open AccessPublished:October 02, 2021DOI:https://doi.org/10.1016/j.jsxm.2021.09.004

      Abstract

      Background

      Even though polycystic ovary syndrome (PCOS) is a common reproductive disorder affecting young women, its impact on their sexual health is not well known.

      Aim

      To examine the different aspects of female sexuality in young women with PCOS and attempt to associate hormonal changes and ovulatory status with their sexual function.

      Methods

      Anthropometric characteristics, hormonal levels and sexual function based on the Female Sexual Function Index (FSFI) questionnaire were assessed in 76 young women with PCOS and 133 matched controls.

      Outcomes

      Sexual function is significantly impaired in young women with PCOS.

      Results

      Women with PCOS demonstrated lower scores than controls in arousal (5.04 ± 1.19 vs 4.48 ± 1.44, P < .001), lubrication (5.29 ± 1.17 vs 4.69 ± 1.54, P < .001), orgasm (4.78 ± 1.40 vs 4.11 ± 1.61, P = .001), satisfaction (5.22 ± 1.10 vs 4.78 ± 1.31, P = .016), and total score of the FSFI (29.51 ± 5.83 vs 26.76 ± 6.81, P < .001), even after correction for BMI. When corrected for total testosterone, the domains of lubrication, satisfaction, and total score of FSFI remained significantly impaired in women with PCOS (P values .037, .024, & .044 respectively). In multivariate logistic regression analysis, after adjusting for the effect of BMI and hormone levels, dysfunction in orgasm, satisfaction and the total FSFI score were still 3–4 times more common in PCOS (adjusted OR [95% CI]: 3.54, P = .020; 2.96, P = .050; 3.87, P = .027). Even though no statistically significant differences were observed between women with ovulatory PCOS and controls, we detected statistically significant differences in all domains of sexual function apart from pain between controls and PCOS women with anovulation (desire P value .04, arousal P value <.001, lubrication P value <.001, orgasm P value .001, satisfaction P value .001 and FSFI total score P value <.001).

      Clinical Implications

      Women with PCOS have compromised sexual function, which is independent of their BMI and highly dependent on their ovulatory status.

      Strengths and Limitations

      This is the first study in women with PCOS that implicates anovulation as a risk factor for sexual impairment in PCOS. Further studies are needed to elucidate the mechanisms implicated and to examine the effect of PCOS therapy on the patients’ sexual function.

      Conclusion

      The adverse effect of PCOS status on the female sexual function is independent of BMI and only partially dependent on hormonal changes characterizing the syndrome. Anovulation appears to be the major determinant of sexual impairment among women with PCOS.
      Mantzou D, Stamou MI, Armeni AK, et al. Impaired Sexual Function in Young Women With PCOS: The Detrimental Effect of Anovulation. J Sex Med 2021;18:1872–1879.

      Key Words

      Introduction

      The aim of this study was to examine for the first time the different aspects of female sexuality in young women of Greek origin with polycystic ovary syndrome (PCOS) who do not seek fertility and to attempt to associate hormonal changes and ovulatory status with their sexual function.
      PCOS is the most common reproductive endocrine disorder in women with a prevalence of 10–15%.
      • Azziz R
      • Carmina E
      • Chen Z
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      Polycystic ovary syndrome.
      PCOS is characterized by anovulation, clinical or biochemical evidence of hyperandrogenism and polycystic morphology in ovarian ultrasound, with several criteria having been established to diagnose it based on the presence of all or some of these characteristics.
      Rotterdam EA-SPcwg.
      Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS).
      • Dunaif A.
      Polycystic ovary syndrome.
      • Azziz R
      • Carmina E
      • Dewailly D
      • et al.
      The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: The complete task force report.
      Apart from the effect of PCOS on menstrual cycles and fertility as well as hyperandrogenism associated symptoms, this complex disorder is associated with many long-term conditions including obesity, insulin resistance and diabetes, dyslipidemia and metabolic syndrome. Importantly, women with PCOS are also in high risk of depression, anxiety, low self-esteem and report a lower quality of life compared to women without the syndrome.
      • Himelein MJ
      • Thatcher SS.
      Polycystic ovary syndrome and mental health: A review.
      • Hahn S
      • Janssen OE
      • Tan S
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      Clinical and psychological correlates of quality-of-life in polycystic ovary syndrome.
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      Determinants of emotional distress in women with polycystic ovary syndrome.
      • Fauser BC
      • Tarlatzis BC
      • Rebar RW
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      Consensus on women's health aspects of polycystic ovary syndrome (PCOS): The Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group.
      • de Niet JE
      • de Koning CM
      • Pastoor H
      • et al.
      Psychological well-being and sexarche in women with polycystic ovary syndrome.
      • Mansson M
      • Norstrom K
      • Holte J
      • et al.
      Sexuality and psychological wellbeing in women with polycystic ovary syndrome compared with healthy controls.
      Research on PCOS has so far mainly focused on prompt diagnosis, treatment, and fertility outcomes. However, research on the psychological and sexual health of women with PCOS has been reported in a more limited manner. Such studies have demonstrated that women with PCOS have consistently been found to have the same frequency of sexual intercourse as other women, but to have lower levels of satisfaction with their sex lives.
      • Hahn S
      • Janssen OE
      • Tan S
      • et al.
      Clinical and psychological correlates of quality-of-life in polycystic ovary syndrome.
      ,
      • Mansson M
      • Norstrom K
      • Holte J
      • et al.
      Sexuality and psychological wellbeing in women with polycystic ovary syndrome compared with healthy controls.
      ,
      • Elsenbruch S
      • Hahn S
      • Kowalsky D
      • et al.
      Quality of life, psychosocial well-being, and sexual satisfaction in women with polycystic ovary syndrome.
      The sexual difficulties observed may be attributed to the high rate of psychological symptoms in women with PCOS,
      • Elsenbruch S
      • Benson S
      • Hahn S
      • et al.
      Determinants of emotional distress in women with polycystic ovary syndrome.
      and specific domains of sexual function have been studied and found to be impaired in such women including arousal,
      • Mansson M
      • Norstrom K
      • Holte J
      • et al.
      Sexuality and psychological wellbeing in women with polycystic ovary syndrome compared with healthy controls.
      desire,
      • Conaglen HM
      • Conaglen JV.
      Sexual desire in women presenting for antiandrogen therapy.
      lubrication,
      • Hashemi S
      • Ramezani Tehrani F
      • Farahmand M
      • et al.
      Association of PCOS and its clinical signs with sexual function among Iranian women affected by PCOS.
      and orgasm.
      • Stovall DW
      • Scriver JL
      • Clayton AH
      • et al.
      Sexual function in women with polycystic ovary syndrome.
      On the other hand, several studies have not shown a difference in sexual function between women with and without PCOS.
      • Ferraresi SR
      • Lara LA
      • Reis RM
      • et al.
      Changes in sexual function among women with polycystic ovary syndrome: A pilot study.
      • Zueff LN
      • Lara LA
      • Vieira CS
      • et al.
      Body composition characteristics predict sexual functioning in obese women with or without PCOS.
      • Morotti E
      • Persico N
      • Battaglia B
      • et al.
      Body imaging and sexual behavior in lean women with polycystic ovary syndrome.
      • Ercan CM
      • Coksuer H
      • Aydogan U
      • et al.
      Sexual dysfunction assessment and hormonal correlations in patients with polycystic ovary syndrome.
      As hormonal changes that occur during the normal menstrual cycle can affect the sexual desire and function,
      • Shirazi TN
      • Bossio JA
      • Puts DA
      • et al.
      Menstrual cycle phase predicts women's hormonal responses to sexual stimuli.
      several studies have attempted to examine the relationship between hormonal changes in PCOS and sexual function with data being conflicting. In a study of 92 women with PCOS, those with total testosterone levels more than 1 SD above the group mean had better sexual function than other women.
      • Stovall DW
      • Scriver JL
      • Clayton AH
      • et al.
      Sexual function in women with polycystic ovary syndrome.
      Similarly, total testosterone levels correlated positively with sexual function in 2 studies
      • Mansson M
      • Norstrom K
      • Holte J
      • et al.
      Sexuality and psychological wellbeing in women with polycystic ovary syndrome compared with healthy controls.
      but negatively in another.
      • Ercan CM
      • Coksuer H
      • Aydogan U
      • et al.
      Sexual dysfunction assessment and hormonal correlations in patients with polycystic ovary syndrome.
      In addition, randomized controlled trials of the impact of treatment of PCOS on sexual function are limited. In an observational study of women with hyperandrogenism treated with cyproterone acetate a decrease in sexual desire was found after 1 year of therapy.
      • Conaglen HM
      • Conaglen JV.
      Sexual desire in women presenting for antiandrogen therapy.
      In contrast, an open-label observational study of women treated with metformin for PCOS found an improvement in sexual satisfaction after 6 months of treatment.
      • Hahn S
      • Benson S
      • Elsenbruch S
      • et al.
      Metformin treatment of polycystic ovary syndrome improves health-related quality-of-life, emotional distress and sexuality.
      Importantly, most studies have used small samples and have recruited women attending gynecology clinics, often for infertility, which might bias the results, as fertility seeking can be an additional stressor to a woman's life. Furthermore, each of those studies has been performed in women of different cultural and social backgrounds, which could have affected their psychological and sexual function.

      Materials and Methods

       Subjects

      We studied 76 women aged 20–30-year-old with PCOS and 133 healthy female controls. Patients with PCOS were recruited from the Division of Endocrinology of the University Hospital of Patras; PCOS was defined based on the Androgen Excess Society criteria,
      • Azziz R
      • Carmina E
      • Dewailly D
      • et al.
      The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: The complete task force report.
      in order to obtain a homogeneous group of hyperandrogenic patients and limit the impact of PCOS heterogeneity on the studied outcomes. Healthy controls were recruited among attendees of 2 workshops on female sexuality conducted in the Universities of Athens and Patras organized by our department.
      • Armeni AK
      • Assimakopoulos K
      • Marioli D
      • et al.
      Impact of estrogen receptor alpha gene and oxytocin receptor gene polymorphisms on female sexuality.
      Controls had normal ovulatory menstrual cycles (28–35 days) and no clinical/biochemical hyperandrogenemia. All women recruited were sexually active in the last 4 weeks, participated voluntarily in the study and did not seek fertility. Exclusion criteria for both the women with PCOS and the healthy controls were chronic diseases, psychiatric disorders, use of drugs that could affect the hypothalamus–pituitary–gonadal axis (eg. oral contraceptive pills, GnRH agonists, antipsychotics, antidepressants, chemotherapeutic agents). Women on such drugs were excluded due to their inhibited ovarian hormone secretion. All eligible control subjects were students in higher education institutions. The socioeconomic background of the women with PCOS was similar to controls. The conduct of the study was approved by the Institutional Review Board of Patras Medical School, functioning according to the Declaration of Helsinki. All participants provided written informed consent before study entry.

       Assessment of Demographic, Anthropometric Characteristics, and Hormonal Measurements

      Height and weight were measured, and body mass index (BMI) (kg/m2) was calculated. Hormonal determinations of follicular (first to fourth day of menstrual cycle) and luteal phase (18th–21st day of menstrual cycle) were performed following spontaneous or progesterone-induced menstrual bleeding. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, total testosterone, and sex hormone-binding globulin (SHBG) were measured, whereas Free Androgen Index (FAI) was calculated
      • Vermeulen A
      • Verdonck L
      • Kaufman JM.
      A critical evaluation of simple methods for the estimation of free testosterone in serum.
      on follicular phase. Progesterone levels were measured on luteal phase of the menstrual cycle. Hormonal levels were determined by Chemiluminescence (Elecsys 2010, Roche Diagnostics GmbH, Mannheim, Germany). The intra- and inter-assay precision CV (%) values were 0.7–1.2% and 1.6–2.2% for LH, 2.5–2.8% and 3.6–4.5% for FSH, 1.1–6.7% and 1.9–10.6% for Estradiol, 2.1–14.8% and 2.5–18.1% for Testosterone, 1.1–1.7% and 1.8–4.0% for SHBG, and 2.4–11.9% and 3.3–22.5% for Progesterone, respectively. The values of the lower detection limits were 0.100 mIU/mL for LH, 0.100 mIU/mL for FSH, 5.0 pg/mL for Estradiol, 0.025 ng/mL for Testosterone, 0.35 nmol/L for SHBG and 0.05 ng/mL for Progesterone. Ovulation was defined as luteal phase progesterone ≥8ng/mL, while luteal phase progesterone <8 ng/mL was considered to indicate anovulation.

       Assessment of Sexual Function

      Sexual function was measured by the Greek version of the Female Sexual Function Index (FSFI),
      • Rosen R
      • Brown C
      • Heiman J
      • et al.
      The Female Sexual Function Index (FSFI): A multidimensional self-report instrument for the assessment of female sexual function.
      a 19-item multiple choice questionnaire. The FSFI is an internationally accepted and reliable instrument for rating female sexual function for research or clinical use. It measures 6 domains, namely sexual desire, arousal (subjective), lubrication, orgasm, satisfaction, and pain over the past 4 weeks. The 6 domain scores are summed to produce a full-scale score. For all FSFI domains, higher values indicate a better level of function, and in each domain, there is a threshold differentiating normal function from dysfunction.
      • Rosen R
      • Brown C
      • Heiman J
      • et al.
      The Female Sexual Function Index (FSFI): A multidimensional self-report instrument for the assessment of female sexual function.
      In particular, dysfunction was defined as scores <4.28 in the desire domain, <5.08 in the arousal domain, <5.45 in the lubrication domain, <5.05 in the orgasm domain, <5.04 in the satisfaction domain, and <5.51 in the pain domain. These cutoffs represent the weighed means per FSFI domain in a large cohort of control women used to validate the FSFI questionnaire.
      • Wiegel M
      • Meston C
      • Rosen R.
      The female sexual function index (FSFI): Cross-validation and development of clinical cutoff scores.
      The threshold we used to define dysfunction based on the total FSFI score (<26.55) has been shown to have the lowest rate of misclassification in FSFI validation studies.
      • Wiegel M
      • Meston C
      • Rosen R.
      The female sexual function index (FSFI): Cross-validation and development of clinical cutoff scores.
      Furthermore, all participants were screened for anxiety and depression using the Greek version of the Hospital Anxiety and Depression Scale (HADS).
      • Zigmond AS
      • Snaith RP.
      The hospital anxiety and depression scale.

       Statistical Analyses

      Statistical analysis was conducted using IBM SPSS Statistics for Windows, version 25.0 (IBM Corp., Armonk, NY, USA). Parameters were tested for normality with the Kolmogorov–Smirnov test. All parameters are presented as mean value ± standard deviation (mean ± SD), regardless of their distribution. Comparisons between groups were conducted using the independent samples t-test (2 groups) or 1-way ANOVA (3 groups) for normally distributed data and using the Mann-Whitney U test (2 groups) or the Kruskal-Wallis test (3 groups) for non-normally distributed variables. Adjustments for confounding variables were performed using the general linear model. The Spearman's correlation test was used to assess correlations between parameters of sexuality and hormonal levels. The impact of PCOS status on the presence of dysfunction in each domain of the FSFI was evaluated using a binary logistic regression model in univariate and multivariate analyses (results were expressed as adjusted odds ratios); in this model, PCOS was a categorical independent variable and the presence or absence of dysfunction in each domain of the FSFI was the dichotomous dependent variable. All tests were 2-tailed and a P value of less than .05 was considered significant.

      Results

       Anthropometric Characteristics and Hormonal Evaluation

      Anthropometric and hormonal values of our study population are presented in Table 1. There was no statistically significant difference in the mean age of subjects with and without PCOS (22.17 ± 2.51 and 21.62 ± 1.93, respectively). No statistically significant differences were also observed for height, LH and estradiol. However, women with PCOS had a significantly higher weight and BMI as well as higher total testosterone levels and FAI compared to controls. In contrast, PCOS subjects demonstrated lower SHBG and progesterone compared to controls.
      Table 1Anthropometric characteristics and hormonal profile of controls and subjects with PCOS.
      ParameterControls (N = 133)PCOS subjects (N = 76)P value
      Age (years)21.62 ± 1.9322.17 ± 2.51.071
      Height (m)1.65 ± 0.051.66 ± 0.06.112
      Weight (kg)59.89 ± 12.1565.99 ± 15.85.001
      BMI (kg/m2)22.1 ± 4.023.97 ± 5.39.004
      FSH (mIU/mL)6.54 ± 1.545.75 ± 1.69.001
      LH (mIU/mL)5.95 ± 2.217.10 ± 4.45.094
      Estradiol (pg/mL)43.64 ± 15.244.80 ± 15.80.338
      Total testosterone (ng/mL)0.31 ± 0.090.61 ± 0.12<.001
      SHBG (nmol/L)69.55 ± 29.7854.03 ± 32.90<.001
      FAI1.95 ± 1.415.38 ± 3.89<.001
      Progesterone (ng/mL)9.77 ± 7.394.84 ± 5.84<.001
      Bold values represent statistically significant P values.

       Sexual Function in Women With PCOS Compared to Controls

      As shown in Table 2, women with PCOS demonstrated lower scores in arousal, lubrication, orgasm, satisfaction, and total score of the FSFI. Since BMI, progesterone and testosterone levels were significantly different between PCOS and controls, we further analyzed the data corrected for these parameters. Women with PCOS continued to demonstrate lower scores in the same domains, even when corrected for BMI, progesterone, or the combination of BMI, progesterone and testosterone. However, when corrected for total testosterone levels, differences remained significant only for the domains of lubrication, satisfaction, and total score of FSFI. Notably, the effect size of PCOS status in the adjusted models created was small to medium as estimated by the Partial Eta Squared (Table 2). As shown in Table 3, univariate logistic regression analysis showed that patients with PCOS were 2–3 times more likely than controls to present dysfunction in arousal, lubrication, orgasm, satisfaction and total FSFI score. In multivariate analysis, after adjusting for the effect of possible confounders such as BMI and hormone levels, dysfunction in orgasm, satisfaction and the total FSFI score were still 3-4 times more likely in PCOS subjects. Importantly, no statistically significant differences were noted between women with PCOS and controls with regards to their anxiety, depression, and distress scores as evaluated by the HADS (anxiety: PCOS 6.92 ± 4.02/Controls 6.57 ± 3.99, P = .605, depression: PCOS 4.59 ± 3.38/Controls 4.16 ± 2.65, P = .672, distress: PCOS 11.51 ± 6.62/Controls 10.73 ± 5.85, P = .554).
      Table 2FSFI domains and total scores in healthy controls and subjects with PCOS, corrected for BMI, progesterone and total testosterone.
      FSFI domainCONTROLS (Ν = 133)PCOS subjects (Ν = 76)P valueP value (partial Eta squared) [corrected for BMI]P value (partial Eta squared) [corrected for Progesterone]P value (partial Eta squared) [corrected for Testosterone]P value (partial Eta squared) [corrected for BMI, Progesterone & Testosterone]
      Desire4.25 ± 0.954.07 ± 0.98.172
      Arousal5.04 ± 1.194.48 ± 1.44<.001.001 (.05).010 (.05).067 (.02).032 (.05)
      Lubrication5.29 ± 1.174.69 ± 1.54<.001.001 (.06).006 (.05).037 (.02).022 (.06)
      Orgasm4.78 ± 1.404.11 ± 1.61.001.001 (.06).006 (.05).075 (.01).021 (.05)
      Satisfaction5.22 ± 1.104.78 ± 1.31.016.010 (.04).014 (.04).024 (.03).036 (.05)
      Pain4.94 ± 1.554.66 ± 1.85.717
      FSFI total29.51 ± 5.8326.76 ± 6.81<.001.001 (.05).007 (.05).044 (.02).026 (.06)
      Bold values represent statistically significant P values.
      Table 3Binary logistic regression analysis for the presence of dysfunction (dependent variable) in each domain of female sexuality, as assessed by the FSFI score: A. Univariate analysis including only PCOS status (independent variable), and B. Multivariate analysis including PCOS status, BMI, and hormonal levels (independent variables).
      A. Univariate analysisB. Multivariate analysis
      FSFI domainaOR (95% CI)P valueaOR (95% CI)P value
      Desire1.48 (0.82–2.68).190
      Arousal1.92 (1.07–3.43).0292.30 (0.81–6.53).117
      Lubrication2.56 (1.42–4.61).0022.28 (0.79–6.56).127
      Orgasm2.64 (1.47–4.75).0013.54 (1.22–10.22).020
      Satisfaction2.07 (1.14–3.74).0162.96 (1.00–8.84).050
      Pain1.11 (0.63–1.95).714
      FSFI total3.12 (1.58–6.15).0013.87 (1.16–12.89).027
      aOR = adjusted odds ratio (PCOS vs controls); CI = confidence interval. Bold values represent statistically significant P values.

       Hormonal and Ovulation Effect on Sexual Function in Women With PCOS

      To further investigate the factors affecting sexual function in women with PCOS, we analyzed the effect of hormones on the different aspects of sexuality in our patient cohort. We found that in women with PCOS, testosterone was negatively correlated with pain during sexual intercourse (r = 0.257, P = .028), progesterone was positively correlated with satisfaction (r = 0.290, P = .014) and the total score (r = 0.217, P = .05), and LH was negatively correlated with satisfaction and the total score (r = -0.350, P = .002 and r = -0.254, P = .03, respectively). Subsequently, we compared the levels of these hormones in women who presented dysfunction in each FSFI domain vs those who did not. We noted that PCOS women with dysfunction in the domains of satisfaction and total FSFI score had significantly lower progesterone levels compared to their non-dysfunctional counterparts (2.62 ± 3.60 vs 6.96 ± 6.75, P = .002 and 3.18 ± 4.31 vs 5.98 ± 6.48, P = .045, respectively). Additionally, PCOS women with high levels of pain during intercourse demonstrated lower mean testosterone than subjects without such dysfunction (0.57 ± 0.10 vs 0.65 ± 0.13, P = .005).
      Since progesterone appeared to affect the sexual function of PCOS subjects, we performed an additional analysis where we compared PCOS women with ovulatory (progesterone ≥8 ng/mL, N = 22) and anovulatory (progesterone <8 ng/mL, N = 51) cycles with healthy controls. As shown in Table 4, we observed statistically significant differences in most domains among the 3 groups. In post hoc analysis we observed that: (i) there was no statistically significant difference between controls and ovulatory PCOS in any domain; (ii) although there was no statistically significant difference between the ovulatory and anovulatory groups of subjects with PCOS, a trend for higher satisfaction (5.07 ± 1.33 vs 4.53 ± 1.43, P = .06) and arousal (4.75 ± 1.43 vs 4.32 ± 1.47, P = .09) in the ovulatory group was observed; (iii) we detected statistically significant differences in all domains apart from pain between controls and anovulative PCOS women (desire P value .04, arousal P value <.001, lubrication P value <.001, orgasm P value .001, satisfaction P value .001 and FSFI total score P value <.001).
      Table 4Differences in FSFI parameters between healthy controls, subjects with ovulatory PCOS (progesterone ≥8 ng/mL) and anovulatory PCOS (progesterone <8 ng/mL).
      FSFI domainControls (N = 133)Ovulatory PCOS (N = 22)Anovulatory PCOS (N = 51)P value
      Desire4.25 ± 0.954.23 ± 0.953.94 ± 0.99.125
      Arousal5.04 ± 1.194.75 ± 1.434.32 ± 1.47<.001
      Lubrication5.29 ± 1.174.80 ± 1.784.61 ± 1.48.001
      Orgasm4.78 ± 1.404.09 ± 1.933.69 ± 1.48.002
      Satisfaction5.22 ± 1.105.07 ± 1.334.53 ± 1.43.003
      Pain4.94 ± 1.554.51 ± 2.054.68 ± 1.81.837
      FSFI total29.51 ± 5.8327.45 ± 7.6026.20 ± 6.58<.001
      Bold values represent statistically significant P values.

      DISCUSSION

      The present study showed that sexual function is impaired in young women with PCOS relative to healthy controls. Compromised sexual function in PCOS is independent of BMI, while anovulation is the major hormonal determinant of sexual impairment among PCOS patients.
      Sexual function has been recognized as a marker of overall human health. Chronic illnesses have been associated with sexual dysfunction in both men and women and, in turn, sexual dysfunction can have a great impact οn the quality of life in both sexes.
      • Basson R
      • Rees P
      • Wang R
      • et al.
      Sexual function in chronic illness.
      Among disorders of reproduction, PCOS is a chronic condition that has been associated with long term adverse outcomes such as metabolic syndrome and cardiovascular disease. Women with PCOS are at increased risk of psychological distress including anxiety, depressive symptoms,
      • Elsenbruch S
      • Benson S
      • Hahn S
      • et al.
      Determinants of emotional distress in women with polycystic ovary syndrome.
      negative body image
      • Deeks AA
      • Gibson-Helm ME
      • Paul E
      • et al.
      Is having polycystic ovary syndrome a predictor of poor psychological function including anxiety and depression?.
      and demonstrate decreased health-related quality of life compared to controls.
      • Berni TR
      • Morgan CL
      • Berni ER
      • et al.
      Polycystic ovary syndrome is associated with adverse mental health and neurodevelopmental outcomes.
      Studies on the sexual function of PCOS women have been conducted worldwide. Most of them have been limited to small cohorts of distinct cultural backgrounds and the outcomes have been conflicting. For example, in the study by Stovall et al
      • Stovall DW
      • Scriver JL
      • Clayton AH
      • et al.
      Sexual function in women with polycystic ovary syndrome.
      women with PCOS had a significantly lower orgasm/completion score compared with women in the control group. Similarly, in a study of 49 women with PCOS, almost half reported sexual dysfunction.
      • Mansson M
      • Norstrom K
      • Holte J
      • et al.
      Sexuality and psychological wellbeing in women with polycystic ovary syndrome compared with healthy controls.
      Lower levels of desire,
      • Conaglen HM
      • Conaglen JV.
      Sexual desire in women presenting for antiandrogen therapy.
      arousal, lubrication, orgasm and satisfaction have also been reported in PCOS.
      • Hashemi S
      • Ramezani Tehrani F
      • Farahmand M
      • et al.
      Association of PCOS and its clinical signs with sexual function among Iranian women affected by PCOS.
      On the other hand, several studies have shown no association between the presence of PCOS/the hormonal profile that accompanies the diagnosis and sexual dysfunction. In the cross-sectional study by Noroozzadeh et al
      • Noroozzadeh M
      • Tehrani FR
      • Mobarakabadi SS
      • et al.
      Sexual function and hormonal profiles in women with and without polycystic ovary syndrome: A population-based study.
      63 Iranian PCOS subjects were compared to 216 healthy women (18–45-year-old). The study showed no statistically significant difference in total FSFI and each of its specific domain scores between the 2 groups and no significant correlations between hormonal profiles and FSFI scores were found. Similarly, Glowinska et al
      • Glowinska A
      • Duleba AJ
      • Zielona-Jenek M
      • et al.
      Disparate relationship of sexual satisfaction, self-esteem, anxiety, and depression with endocrine profiles of women with or without PCOS.
      showed that sexual satisfaction scores were comparable among women with and without PCOS.
      The controversy of the published studies is also highlighted in several meta-analyses of population-based, case-control and cross-sectional studies that have been conducted trying to address the crucial question of the effect of PCOS on female sexual function. In the study by Loh et al that analyzed 28 observational studies involving 6256 women, the prevalence of sexual dysfunction among women with and without PCOS was 35% and 29.6%, respectively, with no significant difference in total FSFI score between the 2 groups. Women with PCOS, however, had significantly worse scores in the pain and satisfaction subscales; in a sub-analysis including 16 studies that reported the proportion of sexual dysfunction among participants, women with PCOS had 1.32 higher odds of having sexual dysfunction than women without PCOS.
      • Loh HH
      • Yee A
      • Loh HS
      • et al.
      Sexual dysfunction in polycystic ovary syndrome: A systematic review and meta-analysis.
      In contrast, a meta-analysis by Zhao et al of 2,626 participants (mean age 25–36 years) from 10 studies including 1163 women with PCOS, revealed no significant association between PCOS and increased risk of sexual dysfunction.
      • Zhao S
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      • Xie Q
      • et al.
      Is polycystic ovary syndrome associated with risk of female sexual dysfunction? A systematic review and meta-analysis.
      Murgel et al showed in their meta-analysis that despite the potential risk of bias due to the inhomogeneity of study population, sexual function of both PCOS patients and women with regular menstrual cycles seem to be similar.
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      • Santos Simoes R
      • Maciel GAR
      • et al.
      Sexual dysfunction in women with polycystic ovary syndrome: Systematic review and meta-analysis.
      Finally, a recent meta-analysis including 36 studies and reporting on 349,529 patients showed that women with PCOS had lower sexual satisfaction as measured on a visual analogue scale, but no difference in Total Female Sexual Function Index.
      • Thannickal A
      • Brutocao C
      • Alsawas M
      • et al.
      Eating, sleeping and sexual function disorders in women with polycystic ovary syndrome (PCOS): A systematic review and meta-analysis.
      The observed disparities of the resulted outcomes can be explained by the heterogeneous nature and diverse phenotypic presentation of the disease. Importantly, not all women with PCOS have clinical or biochemical evidence of hyperandrogenism, nor have they irregular menstrual cycles. To address these challenges, we conducted a study of hyperandrogenic PCOS women of young reproductive age of Greek origin who did not seek fertility and performed detailed phenotypic and biochemical evaluations to investigate the impact of PCOS and the hormonal changes that accompany the syndrome on female sexuality. Our subject cohort was compared to healthy controls who were also young, did not seek fertility and reported regular sexual activity.
      We found that women with PCOS had a significantly higher weight and BMI as well as higher testosterone levels and FAI compared to controls. Interestingly, women with PCOS demonstrated lower scores in arousal, lubrication, orgasm, satisfaction and total score of the FSFI compared to healthy controls, and were 2–3 times more likely than controls to present dysfunction in these domains. The association of obesity and sexual dysfunction in women is well known,
      • Kerchner A
      • Lester W
      • Stuart SP
      • et al.
      Risk of depression and other mental health disorders in women with polycystic ovary syndrome: A longitudinal study.
      while increasing BMI has been associated with a significant reduction in parameters of sexual function of PCOS women.
      • Stovall DW
      • Scriver JL
      • Clayton AH
      • et al.
      Sexual function in women with polycystic ovary syndrome.
      Given the correlation of PCOS and obesity, the differences in sexual function between PCOS and healthy subjects may be attributed to the higher BMI. However, in our study, even after correction for BMI women with PCOS continued to demonstrate lower scores in the same FSFI domains, suggesting that the increased BMI is not the driving factor for the differences in sexual function noted between PCOS subjects and healthy controls.
      Androgenic hormonal profile has been previously associated with sexual activity in women with or without a partner
      • Caruso S
      • Agnello C
      • Malandrino C
      • et al.
      Do hormones influence women's sex? Sexual activity over the menstrual cycle.
      and testosterone levels have been previously found to impact the sexual function of PCOS women.
      • Stovall DW
      • Scriver JL
      • Clayton AH
      • et al.
      Sexual function in women with polycystic ovary syndrome.
      ,
      • Ercan CM
      • Coksuer H
      • Aydogan U
      • et al.
      Sexual dysfunction assessment and hormonal correlations in patients with polycystic ovary syndrome.
      Thus, we examined whether the higher testosterone levels that our subject cohort demonstrated compared to controls was affecting the observed outcomes. When our data were corrected for total testosterone levels, the domains of lubrication, satisfaction, and total score of FSFI remained significantly different between the 2 groups with women suffering from PCOS displaying lower scores. Importantly, after adjusting for the effect of possible confounders such as BMI and hormone levels, dysfunction in orgasm, satisfaction and the total FSFI score were still 3–4 times more likely in PCOS subjects, suggesting that PCOS affects the sexual function of young women independently of their BMI and hormonal changes. Increased psychological distress, which is common in PCOS
      • Elsenbruch S
      • Benson S
      • Hahn S
      • et al.
      Determinants of emotional distress in women with polycystic ovary syndrome.
      ,
      • Deeks AA
      • Gibson-Helm ME
      • Paul E
      • et al.
      Is having polycystic ovary syndrome a predictor of poor psychological function including anxiety and depression?.
      could contribute to sexual dysfunction. However, our participants with PCOS and controls had similar levels of anxiety and depression and, therefore, the observed differences cannot be attributed to such psychological factors. We may hypothesize that the impaired sexual function in PCOS could be explained by several known (ie, the chronic low-grade inflammatory state which interacts with neuromodulators,
      • Aydogan Kirmizi D
      • Baser E
      • Onat T
      • et al.
      Sexual function and depression in polycystic ovary syndrome: Is it associated with inflammation and neuromodulators?.
      the presence of particular genetic variants
      • Day F
      • Karaderi T
      • Jones MR
      • et al.
      Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria.
      ) or even unknown factors contributing to the pathophysiology of the syndrome.
      It is known that many female mammals demonstrate increased sexual activity during estrus.
      • Wallen K.
      Sex and context: Hormones and primate sexual motivation.
      In contrast, the sexual activity of human females occurs throughout the menstrual cycle. Data on the effect of hormonal changes during the menstrual cycle on sexuality have been controversial, as sexual activity depends on many non-biological factors such as the partner's sexual interest and intention to prevent pregnancy. However, some authors have shown that female sexual initiation could be linked to ovarian cycle phase,
      • Van Goozen SH
      • Wiegant VM
      • Endert E
      • et al.
      Psychoendocrinological assessment of the menstrual cycle: The relationship between hormones, sexuality, and mood.
      and sexual activity of women without a partner appears to be higher during the ovulatory phase and lower during the menses compared to women with a partner.
      • Caruso S
      • Agnello C
      • Malandrino C
      • et al.
      Do hormones influence women's sex? Sexual activity over the menstrual cycle.
      PCOS appears to be the most suitable disease model to investigate the effect of ovulation on sexual function of women, since only a subset of women with PCOS has anovulatory cycles. Indeed, in our analysis we found that within women with PCOS progesterone is positively correlated with satisfaction and the total FSFI score. Importantly, even though there were no differences between controls and hyperandrogenic PCOS women with ovulatory cycles with regards to the sexual function outcomes, when women with anovulatory PCOS were compared to healthy controls, they demonstrated significantly lower scores in almost all domains of sexual function. It seems, therefore, that women with ovulatory PCOS represent a mild phenotype with regards to the compromised sexual function associated with the syndrome, highlighting the important role of the ovulation in the female sexual function. Notably, within our PCOS subjects, higher testosterone levels were associated with lower levels of pain during intercourse. A positive effect of high testosterone in the sexual function of PCOS women has been previously reported,
      • Ferraresi SR
      • Lara LA
      • Reis RM
      • et al.
      Changes in sexual function among women with polycystic ovary syndrome: A pilot study.
      while the influence of endogenous androgens on female sexuality in the general population is questionable.
      • Stuckey BG.
      Female sexual function and dysfunction in the reproductive years: The influence of endogenous and exogenous sex hormones.
      However, vaginal testosterone administration can reduce dyspareunia and increase sexual satisfaction in menopausal women,
      • Pitsouni E
      • Grigoriadis T
      • Douskos A
      • et al.
      Efficacy of vaginal therapies alternative to vaginal estrogens on sexual function and orgasm of menopausal women: A systematic review and meta-analysis of randomized controlled trials.
      suggesting that the role of testosterone in vaginal lubrication is not negligible and our finding is not counter-intuitive. Besides, the presence of clinical symptoms of hyperandrogenism was associated with increased sexual desire, masturbation frequency and romantic interest in women in a recent study including women with and without PCOS,
      • Tzalazidis R
      • Oinonen KA.
      Continuum of symptoms in polycystic ovary syndrome (PCOS): Links with sexual behavior and unrestricted sociosexuality.
      showing that androgen sensitivity could affect female sexual function independently of androgen levels.
      Our study has several limitations. First, the sexual function of the participants was assessed with a single questionnaire (the FSFI) and consequently, some potentially important parameters such as sexual fantasies or sexual distress were not evaluated. Second, hormonal evaluations were conducted using a chemiluminescence immunoassay, which has inferior accuracy compared to the golden standard methods of liquid chromatography or mass spectrometry. Finally, there are some confounders potentially affecting parameters of female sexuality which were not assessed in our study (ie, physical activity, metabolic status, partner status and relationship satisfaction of the participants).

      CONCLUSIONS

      The findings of the present study showed that sexual function is significantly impaired in young women with PCOS. The adverse effect of PCOS status on the female sexual function is independent of BMI and only partially dependent on hormonal changes characterizing the syndrome. Anovulation appears to be the major determinant of sexual impairment among young women with PCOS. Further studies are required to elucidate the mechanisms implicated in the sexual dysfunction of PCOS and to examine the effect of PCOS therapy on the patients’ sexual function.

      STATEMENT OF AUTHORSHIP

      Dimitra Mantzou: Investigation, Data Curation; Maria I. Stamou: Writing - Original Draft, Writing - Review & Editing; Anastasia K. Armeni: Investigation, Data Curation; Nikolaos D. Roupas: Formal Analysis; Konstantinos Assimakopoulos: Methodology, Supervision; George Adonakis: Methodology, Supervision; Neoklis A. Georgopoulos: Conceptualization, Methodology, Investigation, Writing - Review & Editing, Supervision, Project Administration; Georgios K. Markantes: Formal Analysis, Investigation, Data Curation, Writing - Original Draft, Writing - Review & Editing.

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