Abstract
Objective:
To describe the prevalence of female sexual dysfunction in a well-defined polycystic ovary syndrome (PCOS) population and assess the impact of common PCOS treatments on sexual function.
Design:
Secondary analysis of a randomized controlled trial (OWL-PCOS).
Setting:
Two academic medical centers.
Patients:
Women with PCOS (n=114) defined by Rotterdam criteria.
Interventions:
Continuous oral contraceptive pill (OCP) or intensive lifestyle modification (Lifestyle) or the combination (Combined) for 16 weeks.
Main Outcome Measures:
Change in Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R) scores after 16 weeks
Results:
There was no change in total FSFI or FSDS-R score in any treatment group but an increase in the FSFI desire domain subscore was observed in the Lifestyle and Combined treatments, indicating improved sexual desire over the 16-week period (mean score changes of 0.35, p=0.02 and 0.37, p=0.02, respectively). Overall, 33 participants (28.9%) met criteria for sexual dysfunction by FSFI criteria (baseline score ≤26.55). Among this group, FSFI score improved after 16 weeks of Lifestyle (mean score change =2.79, p=0.04) and Combined treatments (mean score change =3.68, p=0.03). There was no change in prevalence of sexual dysfunction in treatment groups at 16 weeks. Use of OCPs did not alter FSFI scores.
Conclusion(s):
Female sexual dysfunction is highly prevalent among women with PCOS. Our findings suggest that common treatments of PCOS, including intensive lifestyle modification and the combination of intensive lifestyle modification and OCPs, have the potential to improve sexual function in these women; the mechanism for these improvements is likely multifactorial.
Capsule:
Female sexual dysfunction is highly prevalent among patients with polycystic ovary syndrome. Intensive lifestyle modification alone or in combination with hormonal contraceptive pills, have the potential to improve sexual function.
Keywords: Polycystic ovary syndrome, female sexual dysfunction, oral contraceptive pills, lifestyle modification
Introduction:
Polycystic ovary syndrome (PCOS), is the most common endocrinopathy in women of reproductive age. Characterized by hyperandrogenism and chronic anovulation, its estimated prevalence is 6–13% when the Rotterdam Criteria are applied (1). Even more common than PCOS, female sexual dysfunction has been reported in up to 40% of premenopausal women in the United States (2). Given the high prevalence of both of these conditions and the hypothesized importance of androgens in sexual function, there has been a growing body of research investigating sexual function among women with PCOS. While some studies have suggested that the hyperandrogenism associated with PCOS has detrimental sexual effects (3), others have not demonstrated a relationship between serum androgen levels and sexual function (4,5) or have suggested improved sexual functioning with higher androgen levels (6). A recent meta-analysis concluded that there are small but significant differences in sexual function subscales indicating impaired sexual function in women with PCOS compared to controls. In addition sexual attractiveness and satisfaction with sex life were impaired, and body image impacted sexuality in women with PCOS (7).
For patients not actively trying to conceive, first-line treatment of PCOS is lifestyle modification for weight loss (typically including caloric restriction, increased physical activity, and behavioral modification) and hormonal contraceptive pills (OCPs) (8). While the primary goal of treatment is to improve the endocrine profile by decreasing weight, improving insulin resistance and decreasing androgen levels, it is not clear how these interventions impact sexual function. Obesity in women with PCOS has been associated with sexual dysfunction (9). Numerous studies in the general population have shown that weight loss is associated with improvement in sexual function (10–14). There is no data on the impact of weight loss in women with PCOS on sexual function. OCPs effectively suppress ovarian hyperandrogenism (15) and, in several cohort studies of women without PCOS, this reduction in androgen levels has been significantly associated with decreased sexual function (16–18). Only one study explored the impact of OCPs in normal weight women with PCOS and reported improvements in some aspects of sexual function at six- and nine-months of treatment (19).
Given the recent meta-analysis findings that suggest women with PCOS may have higher rates of sexual dysfunction, understanding what, if any, effects the first-line treatments have on sexual function is of significant clinical importance. In order to elucidate the impact of intensive lifestyle modification and OCP use on sexual function in a well-characterized PCOS population, we undertook a secondary analysis of data from the OWL-PCOS study (20). We hypothesized that treatments involving lifestyle modification would be associated with improved sexual function scores, while OCP use alone would not.
Materials and Methods:
OWL-PCOS Trial
The OWL-PCOS trial was a randomized, open-label, two-site study investigating the impact of varying preconception intervention on health and live birth rates among women with obesity and PCOS. One hundred and forty nine women were randomized to one of three treatment groups: 1) OCPs given continuously (OCP); 2) intensive lifestyle modification (Lifestyle), consisting of caloric restriction with meal replacements, weight loss medication (sibutramine or orlistat), and behavioral modification instruction; and 3) combined OCP and intensive lifestyle modification (Combined) for a 16-week “preconception” period, as described previously (20).
The participants were 18–40 years of age, with body mass index (BMI) of 27–42 kg/m2, and a diagnosis of PCOS by the modified Rotterdam criteria. All women had ovulatory dysfunction with either a polycystic ovary on transvaginal ultrasound or hyperandrogenism (by elevated testosterone level or Ferrimen-Galwey score). Participants could not be taking confounding medications (i.e. insulin sensitizers or sex steroids) and committed to have vaginal intercourse during the study with the intent of pregnancy. The multi-focal lifestyle modification program included caloric restriction, increased physical activity, and counseling in behavior modification strategies. The OCP group received a 20 mcg ethinyl estradiol/1 mg norethindrone acetate formulation prescribed continuously. Women who completed both Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R) surveys at the baseline visit and at the end of 16 weeks intervention were included in this study (n=114).
The study protocol was approved by the institutional review boards of the Penn State College of Medicine, Hershey, PA and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. The trial was registered at Clinicaltrials.gov (NCT00704912). Enrollment for the original RCT began in October 2008 but was closed from January through March 2010 after the US Food and Drug Administration advisory about safety concerns with sibutramine. Orlistat was subsequently substituted for sibutramine in March 2010. The full protocol and case report forms are publicly available at: http://ctsi.psu.edu/owl-pcos/ and the main outcomes for the study have been published (20).
Sexual Function Assessment
Sexual function was assessed using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R). The FSFI is a self-administered validated questionnaire used to assess female sexual function (21). The questionnaire is considered the gold standard assessment of sexual function and includes 19 questions grouped into six domains (desire, arousal, lubrication, orgasm, satisfaction, and pain). A score of 0–5 or 1–5 is assigned to each response, with the total sexual function score based on a weighted score from the six domains ranging from 2 to 36. Higher scores indicate better sexual function. A score of 26.55 or less indicates a risk of sexual dysfunction (22).
The FSDS-R is a 13-item questionnaire that measures sexually related personal distress in women. Each item requires an answer rated as 0–4 (never [0], rarely [1], occasionally [2], frequently [3], or always [4]). The total score ranges from 0 to 52, with higher scores indicating higher levels of sexual distress. The FSDS-R is identical to the original FSDS except for the addition of one question assessing level of distress related to low sexual desire, which improves the discriminative validity of the instrument to distinguish between women with hypoactive sexual desire disorder and those without sexual dysfunction. A score of 11 or higher indicates sexual distress (23).
Other Screening Tools
The PCOS Health-Related Quality of Life (PCOSQ) questionnaire, which is validated for women with PCOS, was administered at the baseline and follow up visit. It includes five domains: emotional, body hair, infertility, weight, and menstrual problems (24). Each domain score is graded on a scale of 1 (poorest function) to 7 (optimal) with a change of 0.5 approximating the smallest change in score that women feel is important in their daily lives. In addition to collecting self-report data on participants’ history of depression and/or anxiety, they completed a Patient Health Questionnaire (PHQ)-9 to formally screen for depressive symptoms (25).
Serum Assays
All laboratory assays were conducted in a central laboratory (Ligand Core Laboratory, University of Virginia), using the same methods previously described in the OWL-PCOS study. Testosterone was measured using an automated radioimmunoassay (Immulite), which has been shown to be comparable to liquid chromatography mass spectrometry assays (26). All assays had intra- and interassay coefficients of variation of less than 10% (20).
Statistical Analysis
As our primary aim was to assess which treatments were associated with changes in sexual function, participants from the OWL-PCOS study who completed both the FSFI and FSDS-R questionnaires at baseline and at 16 weeks (n=114) were included in this analysis. Summary statistics are reported for baseline characteristics including demographic variables, hormonal parameters, physical and phenotypic characteristics, and sexual function measures in each of the three groups. Differences in baseline measures were assessed using analysis of variance models, Kruskal-Wallis tests, or exact chi-square tests, as appropriate. The change from baseline to end of the study was calculated per person for each sexual function measure. General linear models were fit and contrasts constructed to assess the change from baseline within each treatment group, as well as differences between treatment groups. Sexual dysfunction was defined based on the FSFI total score (FSFI ≤ 26.55) and based on the FSDS-R total score (FSDS-R ≥ 11). Generalized estimating equations with a logit link, an extension of logistic regression to account for correlated data within-subjects, were used to compare the prevalence of sexual dysfunction at baseline versus at 16 weeks within each treatment group and results were quantified using odds ratios (OR) and 95% confidence intervals (CIs).
Spearman correlation coefficients (rs) were used to assess the association between change in FSFI scores and change in other parameters (e.g. change in weight) based on the overall cohort, i.e., three treatment groups combined. All hypothesis tests were two-sided and all analyses were performed using SAS software, version 9.4 (SAS Institute Inc., Cary, NC).
Results:
Baseline Demographics
The baseline demographics of the 114 who completed both FSFI and FSDS-R surveys at the baseline visit and at the end of 16 weeks are displayed by treatment group in Table 1. The treatments were similarly distributed and with no significant differences in age, race, education, and marital status. The prevalence of depressive and anxiety symptoms was similar among the three groups, both by patient self-report and PHQ-9 score. There were also no significant baseline differences in weight, BMI, or clinical and biochemical hyperandrogenism between groups, and the mean BMI for each treatment group was in the class 2 obesity range (35.0–39.9 kg/m2).
Table 1:
Baseline Characteristics of Subjects with PCOS#
| OCP (N=39) | Lifestyle (N=39) | Combined (N=36) | |
|---|---|---|---|
| Mean (SD) | Mean (SD) | Mean (SD) | |
| Demographics | |||
| Age (years) | 29.9 (3.8) | 28.8 (3.5) | 28.3 (4.2) |
| Hispanic: N (%) | 5 (12.8%) | 4 (10.3%) | 4 (11.1%) |
| Race: N (%) | |||
| Caucasian | 30 (76.9%) | 27 (69.2%) | 23 (63.9%) |
| Black/African-American | 7 (17.9%) | 5 (12.8%) | 11 (30.6%) |
| Other/multi-racial | 2 (5.1%) | 7 (17.9%) | 2 (5.6%) |
| Nulliparous: N (%) | 30 (76.9%) | 33 (84.6%) | 33 (91.7%) |
| Married: N (%) | 35 (89.7%) | 27 (69.2%) | 27 (75.0%) |
| High school graduate: N (%) | 36 (92.3%) | 38 (97.4%) | 35 (97.2%) |
| Self-reported history: N (%) | |||
| Depression only | 8 (21.1%) | 6 (15.4%) | 8 (22.2%) |
| Anxiety only | 3 (7.9%) | 5 (12.8%) | 5 (13.9%) |
| Depression and/or Anxiety | 10 (26.3%) | 8 (20.5%) | 10 (27.8%) |
| PHQ-9 Score (Total) | 4.8 (3.9) | 5.5 (5.4) | 4.4 (3.4) |
| PCOSQ Score | |||
| Body Hair Domain | 4.3 (1.8) | 4.0 (1.9) | 3.9 (1.6) |
| Emotion Domain | 4.8 (1.3) | 4.5 (1.2) | 4.5 (1.2) |
| Infertility Domain | 3.2 (1.4) | 3.0 (1.4) | 2.5 (1.4) |
| Menstrual Domain | 4.1 (1.2) | 3.9 (1.0) | 4.2 (1.0) |
| Weight Domain | 3.0 (1.6) | 2.8 (1.4) | 2.8 (1.7) |
| Biometric | |||
| Weight (kg) | 93.9 (14.8) | 96.3 (15.7) | 94.8 (15.4) |
| BMI (kg/m2) | 35.0 (4.2) | 35.2 (4.6) | 35.4 (4.6) |
| Ferriman-Gallwey Hirsutism Score | 16.7 (8.1) | 19.7 (8.7) | 17.3 (9.3) |
| Hormone Values | |||
| Testosterone (ng/dl)* | 58.7 (41.4, 74.6) | 54.9 (33.4, 71.2) | 58.4 (38.3, 79.0) |
| SHBG (nmol/L)* | 25.7 (19.4, 34.2) | 27.0 (21.2, 38.1) | 27.1 (18.6, 44.5) |
| FAI* | 7.5 (5.2, 12.9) | 6.5 (4.0, 8.8) | 6.3 (4.6, 9.6) |
| Estradiol (pg/ml) | 56.0 (44.5) | 52.0 (34.3) | 56.4 (47.7) |
No significant differences between groups
Median (25th percentile, 75th percentile) are reported
As shown in Table 2, the baseline FSFI total scores across groups were similar (OCP 28.6 +/− 5.4 vs Lifestyle 28.0 +/− 5.9 vs Combined 29.6 +/− 5.1; P=0.45). There were also no differences in the FSFI desire, arousal, lubrication, orgasm, satisfaction, or pain domain subscores among groups. Although baseline FSDS-R scores were lowest in the Combined arm, among the three groups there was no statistically significant difference (p=0.06). There was no difference in baseline FSFI or FSDS-R scores between the analytic cohort and the original trial participants who were not included, nor was there differential loss to follow up by treatment group (data not shown).
Table 2:
Baseline Sexual Function Assessment#
| OCP (N=39) | Lifestyle (N=39) | Combined (N=36) | |
|---|---|---|---|
| Mean (SD) | Mean (SD) | Mean (SD) | |
| Female Sexual Function Index (FSFI) Score | 28.6 (5.4) | 28.0 (5.9) | 29.6 (5.1) |
| FSFI: Desire Domain | 3.7 (1.1) | 3.4 (1.0) | 3.8 (1.1) |
| FSFI: Arousal Domain | 4.7 (1.2) | 4.4 (1.2) | 4.8 (1.2) |
| FSFI: Lubrication Domain | 5.4 (1.1) | 5.1 (1.2) | 5.5 (0.8) |
| FSFI: Orgasm Domain | 4.7 (1.4) | 4.8 (1.3) | 4.7 (1.5) |
| FSFI: Satisfaction Domain | 4.8 (1.2) | 4.7 (1.3) | 5.1 (1.4) |
| FSFI: Pain Domain | 5.5 (1.0) | 5.5 (1.0) | 5.6 (0.8) |
| Female Sexual Distress (FSDS-R) Score* | 4.0 (0.0, 8.0) | 4.0 (1.0, 13.0) | 1.0 (0.0, 6.0) |
| Sexual Dysfunction | N (%) | N (%) | N (%) |
| FSFI ≤ 26.55 | 11 (28.2%) | 13 (33.3%) | 9 (25.0%) |
| FSDS-R ≥11 | 8 (20.5%) | 10 (25.6%) | 8 (22.2%) |
No significant differences between groups
Median (25th, 75th) percentiles are reported
Overall, 33 participants (28.9%) met criteria for sexual dysfunction by FSFI criteria (baseline total FSFI score ≤ 26.55) and 26 participants (22.8%) had sexual dysfunction by FSDS-R criteria (baseline total FSDS-R score ≥ 11). The prevalence of baseline sexual dysfunction was similar across treatments, using both the FSFI and FSDS-R criteria (Table 2). Women with sexual dysfunction based on FSFI score had significantly lower scores on all PCOSQ domains (emotion, weight, menstrual, infertility domains p<0.01 and body hair p<0.05) and significantly higher PHQ −9 scores (p<0.01).
Changes after 16-week Intervention in each treatment group
There was no change in total FSFI score in any treatment group at 16-weeks compared to baseline (Table 3). However, an increase in the FSFI desire domain subscore was observed in the Lifestyle and Combined treatments indicating improved sexual desire over the 16-week period (mean score changes of 0.35, p=0.02 and 0.37, p=0.02, respectively). Participants in the Lifestyle arm also experienced a trend towards lower total FSDS-R scores, suggesting reduced sexual distress (mean score change −1.97, p=0.06). In contrast, the FSDS-R score also did not change significantly in the Combined group. Patients in the OCP arm did not experience change in any of the FSFI domains or in total FSDS-R score over the follow-up period. Between group comparisons were also performed and there were no differences in change in FSFI or FSDS-R between treatment groups (data not shown).
Table 3:
Changes in Sexual Function in Each Treatment Arm Compared to Baseline Scores
| OCP (n=39) | Lifestyle (n=39) | Combined (n=36) | ||||
|---|---|---|---|---|---|---|
| Mean Change (95% CI) | P-value | Mean Change (95% CI) | P-value | Mean Change (95% CI) | P-value | |
| Female Sexual Function Index (FSFI) Score | 0.02 (−1.34, 1.39) | 0.98 | 1.16 (−0.20, 2.53) | 0.09 | 1.02 (−0.40, 2.44) | 0.16 |
| FSFI: Desire Domain | 0.08 (−0.22, 0.37) | 0.60 | 0.35 (0.06, 0.65) | 0.02 | 0.37 (0.06, 0.67) | 0.02 |
| FSFI: Arousal Domain | −0.13 (−0.47, 0.20) | 0.44 | 0.25 (−0.08, 0.59) | 0.14 | 0.01 (−0.34, 0.36) | 0.96 |
| FSFI: Lubrication Domain | −0.13 (−0.42, 0.16) | 0.37 | 0.12 (−0.16, 0.41) | 0.40 | 0.17 (−0.13, 0.47) | 0.27 |
| FSFI: Orgasm Domain | −0.01 (−0.39, 0.37) | 0.96 | 0.08 (−0.30, 0.46) | 0.67 | 0.21 (−0.19, 0.61) | 0.29 |
| FSFI: Satisfaction Domain | 0.23 (−0.09, 0.54) | 0.16 | 0.25 (−0.07, 0.56) | 0.13 | 0.20 (−0.13, 0.53) | 0.23 |
| FSFI: Pain Domain | −0.01 (−0.30, 0.28) | 0.94 | 0.10 (−0.18, 0.39) | 0.48 | 0.07 (−0.23, 0.36) | 0.66 |
| Female Sexual Distress (FSDS-R) Score | −1.03 (−3.10, 1.05) | 0.33 | −1.97 (−4.05, 0.10) | 0.06 | −1.64 (−3.80, 0.52) | 0.14 |
Changes after 16 weeks in women with sexual dysfunction
Among the subset of women with sexual dysfunction at baseline (total FSFI scores ≤26.55, n=33), the Lifestyle and Combined treatment groups showed significant improvements in total FSFI score (mean score changes of 2.79, p=0.04 and 3.68, p=0.03, respectively) (Table 4). Improvements in individual FSFI domains included the arousal domain in the Lifestyle group (mean score change 0.72, p=0.03) and desire and satisfaction domains in the Combined group (mean score change 0.87, p=0.006 and mean score change 0.98, p=0.02, respectively) (Table 4). These improvements in sexual function are further supported by significant reductions in FSDS-R scores in both of these groups (mean score changes of −6.38, p=0.02 and −6.89, p=0.04, respectively) (Table 4). There were also no differences in change in FSFI or FSDS-R scores between the treatment groups (data not shown).
Table 4:
Changes in Sexual Function Among Participants with Sexual Dysfunction at Baseline (FSFI ≤ 26.55)
| OCP (n=11) | Lifestyle (n=13) | Combined (n=9) | ||||
|---|---|---|---|---|---|---|
| Mean Change (95% CI) | P-value | Mean Change (95% CI) | P-value | Mean Change (95% CI) | P-value | |
| Female Sexual Function Index (FSFI) Score | 2.51 (−0.40, 5.42) | 0.09 | 2.79 (0.12, 5.47) | 0.04 | 3.68 (0.46, 6.89) | 0.03 |
| FSFI: Desire Domain | 0.44 (−0.10, 0.98) | 0.11 | 0.51 (0.01, 1.00) | 0.05 | 0.87 (0.27, 1.46) | 0.006 |
| FSFI: Arousal Domain | 0.33 (−0.36, 1.02) | 0.34 | 0.72 (0.08, 1.35) | 0.03 | 0.57 (−0.19, 1.33) | 0.14 |
| FSFI: Lubrication Domain | 0.22 (−0.46, 0.90) | 0.52 | 0.37 (−0.26, 1.00) | 0.24 | 0.60 (−0.15, 1.35) | 0.11 |
| FSFI: Orgasm Domain | 0.40 (−0.49, 1.29) | 0.37 | 0.52 (−0.30, 1.34) | 0.20 | 0.80 (−0.19, 1.79) | 0.11 |
| FSFI: Satisfaction Domain | 1.02 (0.29, 1.74) | 0.008 | 0.40 (−0.27, 1.07) | 0.23 | 0.98 (0.17, 1.78) | 0.02 |
| FSFI: Pain Domain | 0.11 (−0.46, 0.68) | 0.70 | 0.28 (−0.25, 0.80) | 0.29 | −0.13 (−0.77, 0.50) | 0.67 |
| Female Sexual Distress (FSDS-R) Score | −4.09 (−9.92, 1.74) | 0.16 | −6.38 (−11.75, −1.02) | 0.02 | −6.89 (−13.34, −0.44) | 0.04 |
Despite improvements in total FSFI score for those with baseline sexual dysfunction, there was no change in prevalence of sexual dysfunction (by FSFI criteria) in any treatment group at 16 weeks: OCP: OR 1.00 (95% CI 0.50–2.02), Lifestyle: OR 0.60 (95% CI 0.30–1.20), and Combined: OR 0.48 (95% CI 0.21–1.14) (Supplemental Figure 1). When defined by FSDS-R score, a reduction in prevalence of sexual dysfunction at 16 weeks was observed in the Combined treatment group (OR 0.21, 95% CI 0.06–0.74, p=0.02); (Supplemental Figure 1). A subgroup analysis was performed of patients who met both FSFI and FSDS-R criteria for sexual dysfunction (n=9 in Lifestyle group, n=6 in OCP group, and n=6 in Combined group). After the 16-week intervention period, findings in this “combined outcome” group were similar to those observed in the FSDS-R >=11 alone group. Specifically, a reduction in prevalence of sexual dysfunction was observed (OR 0.29, 95% CI 0.09–0.98, p=0.05).
Correlations with change in sexual function scores
As previously reported, patients in the Lifestyle and Combined groups achieved significant weight loss during the 16-week period compared with the OCP group (P < .0001) (20). However, there was no association between change in weight and change in total FSFI score (rs=−0.10, 95% CI −0.28–0.09) or between change in weight and change in desire domain subscore (rs=−0.16, 95% CI −0.34–0.02). Further, there was no association between change in the PCOSQ weight domain subscore and change in total FSFI score (rs=0.12, 95% CI −0.07–0.30) or the desire domain subscore (rs=−0.04, 95% CI −0.14–0.23). To examine the association between depression and sexual dysfunction we examined the association between change in PHQ-9 score and change in total FSFI score and found a weak correlation (rs=−0.19, 95% CI −0.36, −0.01).
In considering changes in hormonal parameters, the OCP and Combined treatment groups showed significant decreases in serum testosterone levels (P < .0001) and increases in serum sex hormone-binding globulin levels (P < .0001) compared with Lifestyle alone (20). However, there was no association between changes in these hormonal parameters and changes in total FSFI score, the FSFI desire domain subscore, or the FSDS-R (data not shown).
Discussion:
To our knowledge, this is the first study to both describe the prevalence of female sexual dysfunction in a well-defined PCOS population and assess the impact of both pharmacotherapy and lifestyle therapy on sexual function. Nearly 30% of patients with PCOS had sexual dysfunction based on the FSFI score and this group had lower quality of life scores and higher depression scores. For this subgroup of women, treatment with either intensive lifestyle modification or the combination of OCPs and intensive lifestyle modification resulted in significant improvement in sexual function (higher total FSFI scores) and reduced sexual distress (lower FSDS-R scores). We did not observe any change in either measure of sexual function among patients who received treatment with OCPs alone.
Several studies of the general population have found an association between weight loss and improved sexual function (10–14). Specifically, women with severe obesity report greater sexual dysfunction (11) and significant improvements in sexual function are observed in those who experience the greatest weight loss as seen after bariatric surgery (~30% of body weight) (12). While statistically significant weight loss was observed in patients randomized to the Lifestyle and Combined groups in our study, there was no change in total FSFI score in either treatment group at 16-weeks compared to baseline; though improvements in the desire doman were observed. The modest magnitude of the weight loss in these groups (~6% of body weight) (20) may explain the differences in findings although when we specifically examined women with sexual dysfunction to observed improvements in sexual function. Alternatively, the association between weight loss and sexual function may be mediated by the direct and indirect effects of chronic physical exercise (27) and/or other factors related to PCOS (i.e. body image, depression, and use of OCPs) (28).
OCPs have long been a mainstay treatment for patients with PCOS who are not attempting to conceive, however only one prospective study has investigated the impact of OCPs on sexual function in women with PCOS (19). In that study, 56 normal weight women with PCOS were given 30 mcg ethinyl estradiol/2 mg chlormadinone acetate for nine months. Sexual behavior was assessed using the self-administered Short Personal Experience Questionnaire (SPEQ) and improvements in satisfaction with sexual activity, orgasm by intercourse, and dyspareunia were observed after the sixth and ninth cycles (compared to baseline). Conversely, in our study, no significant changes in total FSFI score, FSFI domain subscores, or total FSDS-R score were observed among those treated with OCPs. These conflicting results may be secondary to differences in the patient population (normal weight vs obese), the progestin component of OCP (norethindrone vs chlormadinone), or in the instruments used to measure sexual function (SPEQ vs FSFI and FSDS-R) between the two studies.
Few placebo-controlled randomized trials have investigated the impact of OCPs on sexual function in the general population (29–31). In a systematic review of 36 studies (prospective and retrospective, controlled and uncontrolled), published between 1975 and 2011 and including over 13,000 women, Pastor et al found that 21.7% of the OCP users reported an increase, 63.6% no change, and 14.7% a decrease in sexual desire (32). Based on these findings, a recent position statement from the European Society of Sexual Medicine (ESSM) concluded: “In the vast majority of the cases, the use of combined oral contraceptives resulted in an increase or no change in sexual desire (Level 2; Grade B)” (33). While our study adds to the body of literature suggesting that OCPs do not impair sexual desire, further studies are warranted to investigate the impact of this intervention over a longer duration of time and other domains of sexuality (including lubrication) – particularly in a PCOS population.
The focus of PCOS treatment has primarily been aimed at symptom management and preventing long-term complications. There is growing recognition of the detrimental impact of PCOS on health-related quality of life (34–36). Though the prevalence of sexual dysfunction in our study population was not higher than that of the general population, a finding consistent with multiple recent meta-analyses (37–39), our estimate that nearly one-third of young women with PCOS report sexual dysfunction is clinically significant. In this group of women we found significantly lower scores on all PCOSQ domains. Both lifestyle modification alone and combined with OCPs favorably affected sexual function scores in women with sexual dysfunction. In a prior study we have shown that all 3 treatments also improved PCOSQ scores (36) indicating an overall positive impact of these first line interventions. In their position statement, the ESSM provides an evidence-based algorithm for assessing and managing possible sexual dysfunctions related to the use of OCPs (33). Similarly, it seems appropriate to implement a patient-reported outcome measure like the FSFI into the clinical assessment of all women with PCOS – both as an initial screening tool and an ongoing assessment of the effect of treatment on this important area of quality of life and psychosocial functioning.
Sexual function is a complex biopsychosocial experience influenced by many factors. It is thus important to elucidate what aspects of common PCOS treatments drive the observed improvements among patients with sexual dysfunction. As our findings suggest improvements in sexual function maybe driven by factors other than obesity and hyperandrogenism, we hypothesize that reductions in other psychosocial risk factors may mediate improvements in sexual function. Several recent studies have reported that women with PCOS have increased body image distress, as well as depressive and anxiety symptoms (40–42) and therapeutic interventions aimed at improving body image may decrease depressive and anxiety symptoms and increase self-esteem (42). Although our study was not designed to assess these relationships, we found improvements in depressive symptoms (as measured by PHQ-9 scores) were weakly associated with improvements in total FSFI scores. Further studies are needed to directly assess the impact of change in anxiety, depression and body image distress scores on sexual function in PCOS.
Limitations of our study include the absence of a “no treatment” group, making it difficult to assess whether improvement in scores was due to study participation rather than specific interventions. As is the case with all clinical trials, it is possible that participants modified their behavior in response to their awareness of being observed (Hawthorne effect) or that there was selection bias among those who agreed to participate in the study (trial effect). However, the disparate results in the OCP arm suggest that study participation alone cannot explain our findings. Further, while we observed significant improvements in sexual function with short-duration interventions, we are unable to confirm whether these improvements will be sustained over longer intervention durations. We chose to use an OCP containing norethindrone, a moderately androgenic progestin, as it was well-tolerated in a previous study by our group (15). While our findings may therefore not be generalizable to other OCP formulations, correlations between indices of androgenicity and the various measures of sexuality are inconsistent (43). Additionally, our results may not be generalizable to PCOS patients of normal weight as all study participants wer overweight or obese. Our study has several strengths including a randomized trial of three treatment interventions in well-characterized women with PCOS and the use of multiple validated assessments of sexual function, as well as tools specifically validated in patients with PCOS (HRQOL).
Conclusions:
Our study confirms that female sexual dysfunction is highly prevalent in PCOS which, as the most common endocrinopathy in women of reproductive age, represents a large number of affected women. Our findings support routine screening for sexual dysfunction as suggested by the International PCOS guidelines (7). Common treatments of PCOS, including both lifestyle modifications alone or the combination of lifestyle modification and OCPs, have the potential to improve sexual function. Although our study did not observe any significant effects of OCP on sexual function, future studies should investigate the impact of longer durations of these first line intervention.
Supplementary Material
Supplemental Figure 1: Change in Prevalence of Sexual Dysfunction based on A) FSFI and B) FSDS-R
Acknowledgements:
This work was supported by the Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD), National Center for Research Resources, and the National Center for Advancing Translational Sciences at the National Institutes of Health through Grants R01 HD056510 (to R.S.L.), UL1 TR000127 (Penn State Clinical and Translational Institute), and U54 HD29834 (UVA Core Ligand Assay Core of the Specialized Cooperative Centers Program in Reproduction of the NICHD).
Footnotes
Conflicts of Interest: None
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Supplementary Materials
Supplemental Figure 1: Change in Prevalence of Sexual Dysfunction based on A) FSFI and B) FSDS-R