The Metabolic Syndrome: a Cause of Sexual Dysfunction in Women

K Esposito; M Ciotola; R Marfella; D Di Tommaso; L Cobellis; D Giugliano

Int J Impot Res. 2005;17(3):224-226. 

Abstract and Introduction

Abstract

Female sexual dysfunction (FSD) is a significant public health problem. We assessed the prevalence of FSD in premenopausal women with the metabolic syndrome as compared to the general female population. Compared with the control group ( N =80), women with the metabolic syndrome ( N =120) had reduced mean full Female Sexual Function Index (FSFI) score (23.2 ± 5.4 vs 30.1 ± 4.7, P <0.001), reduced satisfaction rate (3.5 ± 1.1 vs 4.7 ± 1.2, P <0.01), and higher circulating levels of C-reactive protein (CRP: 2.2 (0.6/4.9) vs 0.8 (0.2/2.9) mg/l, median (interquartile range), P =0.01). There was an inverse relation between CRP levels and FSFI score ( r =-0.32, P =0.02). Investigation of female sexuality is suggested for patients with the metabolic syndrome.

Introduction

Female sexual dysfunction (FSD) consists of multiple disorders classified into diagnostic categories of desire, arousal, orgasm, and pain, and has been estimated to affect up to 43% of women in the US.[1] In spite of the high prevalence, which appears to surpass that of male sexual dysfunction, only recently has there been some focus on the sexual problems of women. Although laboratory-based physiological indices of sexual response (eg vaginal blood flow) are available, it has been proposed that the most valid way to assess sexual function in women is in a naturalistic setting, and the self-report technique is the only method currently available for measuring sexual response in an at-home setting.[2] There are only limited data on the prevalence of FSD in obesity[3] and diabetes mellitus,[4] which represent important causes of erectile dysfunction in men;[5,6] to the best of our knowledge, there are no reported studies on the relation between FSD and the metabolic syndrome. Therefore, the aim of the present study was to assess the prevalence of sexual dysfunction in premenopausal women with the metabolic syndrome as compared to the general female population. We elected to study premenopausal women in order to exclude the effect of the altered hormonal milieu of menopause.

Materials and Methods

Patients

Women (age range 20-48 years) were recruited among those attending the outpatient department for metabolic diseases of the teaching hospital at the second University of Naples, Italy. To be enrolled in the study, women had to be in the premenopausal state, to have regular menses, to take no oral contraceptives, to have no endocrinologic or gynecologic disease, and to have three or more of the criteria to meet the diagnosis of the metabolic syndrome, as recommended by the Adult Treatment Panel:[7] (1) abdominal adiposity as defined by a waist circumference of >102 cm in men and >88 cm in women; (2) low serum HDL-cholesterol (<40 mg/dl or <50 mg/dl in men and women, respectively); (3) hypertriglyceridemia as defined by an elevated triglyceride of ≥150 mg/dl; (4) elevated blood pressure as defined by a blood pressure of at least 130/85 mmHg; and (5) abnormal glucose homeostasis as defined by a fasting plasma glucose concentration of ≥110 mg/dl. Exclusion criteria were diabetes mellitus or impaired glucose tolerance, pelvic trauma, urinary incontinence, lower urinary tract symptoms, cardiovascular disease, psychiatric problems, use of drugs, or alcohol abuse. In all, 100 women matched for age (range 20-47 years), body weight, smoking habit, similar premenopausal state, and inclusion/exclusion criteria served as control group. The study was approved by the institutional committee of ethical practice of our institution, and all the study subjects gave informed written consent.

Sexual Questionnaire

Sexual function was assessed by completing the Female Sexual Function Index (FSFI), which is a validated 19-item self-report measure of female sexual function.[2] It is simple to administer and score and is unbiased with respect to age, ethnicity, education, and economic status. The 19 items are assigned to six separate domains of female sexual function. Four domains are related to the four major categories of sexual dysfunction: desire disorder, arousal disorder, orgasmic disorder, and sexual pain disorder. The fifth domain assesses the quality of vaginal lubrication, whether the sixth domain is related to global sexual and relationship satisfaction: it is viewed as the 'quality of life' domain of the scale. Each domain is scored on a scale of zero or 1-6, with higher score indicating better function. The full FSFI scale score, which could be 36 at the highest, was obtained by adding the six domain scores. We considered the functional results to be good when the FSFI score was 30 or more, intermediate between 23 and 29, and poor below 23.

Laboratory

Assays for serum total and high-density lipoprotein cholesterol, triglyceride, and glucose levels were performed in the hospital's chemistry laboratory. High-sensitivity C-reactive protein (CRP) was assayed by immunonephelometry on Behring Nephelometer 2 (Dade Behring, Marburg, Germany).

Statistical Analysis

Data are presented as mean ± s.d., unless stated otherwise. We compared baseline data using a t test for continuous variables and Wilcoxon's test for CRP. We classified all study patients as having 3, 4, or 5 components of the metabolic syndrome and assessed for evidence of a relation of sexual dysfunction across these groups using the Jonckheere-Terpstra test. The χ 2 test was used for comparing proportions of subjects. Spearman's rank correlation coefficients were used to quantify the relationship between FSFI score and CRP levels. All analysis were conducted using SPSS version 9.0 (SPSS Inc., Chicago, Illinois, USA).

Results

The 120 women with the metabolic syndrome were matched with 80 women of the control group for age (40.6 ± 5.7 vs 39.4 ± 3.9 years, P =0.1), body mass index (28.1 ± 3.4 vs 26.9 ± 3 kg/m2, P =0.08), and premenopausal state. Women with the metabolic syndrome showed higher, although not significantly, fasting concentration of serum glucose (102 ± 15 vs 98 ± 14 mg/dl, P =0.06) and triglyceride (167 ± 55 vs 156 ± 48 mg/dl, P =0.15), and lower serum concentration of HDL-cholesterol (48 ± 11 vs 52 ± 13 mg/dl, P =0.06, respectively). Compared with the control group, women with the metabolic syndrome had reduced mean full FSFI score (23.2 ± 5.4 vs 30.1 ± 4.7, P <0.001) and higher circulating concentrations of CRP (2.2 (0.6/4.9) vs 0.8 (0.2/2.9) mg/l, median (interquartile range), P =0.01).

The percentages of women who had FSFI scores normal, intermediate, and poor were for control women 79%, 19% and 2%, respectively, and for women with the metabolic syndrome 56%, 37%, and 9%, respectively ( P <0.01).

Individual analysis of the different domains demonstrated that women with the metabolic syndrome reported significantly lower arousal, orgasm, and lubrication scores ( P <0.01) in comparison with controls (Figure 1). Satisfaction rate was 3.5 ± 1.1 in patients and 4.7 ± 1.2 in controls ( P <0.01). There was a decrease in full FSFI score as the number of components of the metabolic syndrome increased (three components, N =75: 24.9 ± 3.8; four components, N =30: 19.8 ± 3.0; and five components, N =15, 15.7 ± 2.9, P <0.01). FSFI score was negatively associated with CRP levels ( r =-0.32, P =0.02). This correlation was little affected by adjustment for age.

Figure 1.

 

Comparison of the individual domains of the FSFI scores between women with the metabolic syndrome ( N =120) and matched control women ( N =80). *Significant differences between women ( P <0.01).

Discussion

FSD is a significant public health problem. While old data reveal that up to 76% of women had some type of sexual dysfunction, more recent estimates indicate that 43% of women complain of at least one sexual problem.[1] We have demonstrated that women with the metabolic syndrome have an increased prevalence of sexual dysfunctions as compared with matched control women. The inverse relations between the FSFI score, the numbers of components of the syndrome, and CRP levels are intriguing but at present not easily explained. The complexity of the female sexual response and the limited experimental models available has severely hampered progress in this field. Recent studies have begun to unravel peripheral biochemical mediators involved in regulating genital engorgement/swelling and lubrication. The increased genital vasocongestion is thought to occur via activation of the parasympathetic nerves releasing physiological mediators such as nitric oxide;[8] it has been demonstrated that inhibition of nitric oxide synthesis with L-NAME (nitro-L-arginine-methyl ester), a nitric oxide synthase inhibitor, markedly attenuated genital blood flow and administration of sildenafil-enhanced genital blood flow in response to pelvic nerve stimulation.[9] Moreover, CRP, at concentrations known to predict diverse vascular insults, profoundly quenches nitric oxide synthesis, while augmenting the release of endothelin-1 and upregulating adhesion molecules and chemoattractant chemokines, uncovering a proinflammatory and proatherosclerotic phenotype.[10]

It might be speculated that an increased nitric oxide deactivation as a consequence, at least in part, of higher CRP levels may play a role in the greater prevalence of FSD in women with the metabolic syndrome. Clinical studies have shown that in healthy women sildenafil significantly improved arousal, orgasm, and enjoyment when compared with placebo,[11] although these studies are limited and remain controversial.

In conclusion, this study shows that sexual dysfunctions are more prevalent in women with the metabolic syndrome as compared to a general healthy female population. Further investigation is needed to determine the impact of the metabolic syndrome on female sexual function.


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