Subclinical Hypothyroidism Is Not a Risk Factor for Female Sexual Dysfunction in Korean Middle-Aged Women

Introduction

Female sexual dysfunction is a multifactorial disorder affected by physical, psychiatric, and social factors, and it is a relatively common problem in middle-aged women. In Korea, the overall prevalence of female sexual dysfunction in premenopausal women is 55% (1), and a survey of women 40–80 years old revealed that 37% of the women lacked sexual pleasure, and 31% were unable to achieve an orgasm (2). It is known that the prevalence of female sexual dysfunction increases with age and menopause, and the reported prevalence rates in middle-aged women and postmenopausal women were 55–65% and 68–86%, respectively (1,3,4).

Subclinical hypothyroidism is defined as a state of elevated serum thyrotropin (TSH) concentrations with normal free-circulating thyroxine (fT4), and the prevalence of subclinical hypothyroidism is reported to be 4–10% in adults (5 –8). Most patients with subclinical hypothyroidism are asymptomatic, but it can affect quality of life and cause anxiety and depression according to several studies (9 –11).

Endocrinopathies, such as hyperprolactinemia or hypogonadism, have been suggested as one of the major causes of female sexual dysfunction (12 –15). Thyroid disorders including overt hyperthyroidism or hypothyroidism have also been thought to be risk factors for female sexual dysfunction, and psychiatric disturbances such as irritability and depression have been attributed to this problem (12,13,16,17). However, there is a paucity of information regarding the relationship between subclinical hypothyroidism and female sexual dysfunction.

This study examined whether subclinical hypothyroidism is associated with the risk of female sexual dysfunction in middle-aged women who are at risk for both subclinical hypothyroidism and female sexual dysfunction.

Materials and Methods

This cross-sectional study included women who visited the Center for Health Promotion and Optimal Aging at Seoul National University Hospital between February 2010 and December 2011. The screening center provides routine comprehensive health check-ups for healthy asymptomatic persons, and all subjects had independently visited the center. The inclusion criteria were: (a) middle-aged women (≥40 years old), (b) sexual activity with a frequency of at least once per month, and (c) completion of female sexual function index (FSFI) questionnaires. The Institutional Review Board of Seoul National University Hospital approved the study.

According to results from a thyroid function test, cases were divided into two groups: cases with subclinical hypothyroidism and normal controls. Patients were excluded if they had overt hypothyroidism or hyperthyroidism. Subclinical hypothyroidism was defined as a state of elevated serum TSH concentrations (>4.1 μIU/mL) with normal fT4. The reference ranges for TSH and fT4 at the authors' institution are 0.4–4.1 μIU/mL and 0.7–1.8 mg/dL, respectively.

Female sexual function was compared between cases with subclinical hypothyroidism and healthy controls. For this, total FSFI scores and the scores from each area were compared between subjects with subclinical hypothyroidism and healthy controls. The frequency of female sexual dysfunction was also compared between the two groups.

Female sexual function was determined by the Korean version of the FSFI (18), which is a well-structured questionnaire with 19 items regarding female sexual function. The FSFI assesses sexual functioning or problems during the past four weeks in six areas (desire, arousal, lubrication, orgasm, satisfaction, and pain). The scores in each area ranged from 1 to 5 or 0 to 5, and the total score was obtained by the sum of the six domain scores multiplied by the domain factor (0.3–0.6). Female sexual dysfunction was defined as a FSFI score ≤26.55 (19).

For statistical analysis, proportions were compared with Fisher's exact test, and comparisons of continuous variables between groups were performed using the Mann–Whitney U-test. The results were analyzed with SPSS Statistics for Windows v20.0 (IBM Corp., Armonk, NY). A p-value of <0.05 was considered significant.

A sample size calculation was performed to determine how many middle-aged women would be needed to detect a change from 65% to 80% in the frequency of female sexual dysfunction in cases with and without subclinical hypothyroidism. It was estimated that the average frequency of female sexual dysfunction would be 65% in middle-aged women according to previous reports (1,3,4). Assuming an estimated rate of subclinical hypothyroidism of 10%, it was determined that 1111 middle-aged women would be required with 90% power and a type 1 error of 5% and 871 middle-aged women would be required with 80% power and a type 1 error of 5%.

Results

During the study period, 1469 middle-aged sexually active women were approached. Of these, 1262 completed the FSFI questionnaire. After excluding 174 cases with known thyroid disease and two cases with a TSH of >10 μIU/mL, 1086 women were included in the analysis, including 948 women with normal thyroid function and 138 (12.7%) women with subclinical hypothyroidism.

Table 1 shows the clinical characteristics of the women according to the presence or absence of subclinical hypothyroidism. Women with subclinical hypothyroidism were significantly older and had higher frequency of menopause compared with the controls.

Female sexual dysfunction was diagnosed in 741 (68.2%) women in the total population, including 648 of the normal controls and 93 women with subclinical hypothyroidism. Table 2 compares female sexual function according to the presence or absence of subclinical hypothyroidism. The mean FSFI total score and frequency of female sexual dysfunction were not different between the two groups (median total FSFI score (interquartile range): 23.8 (20.2–27.5) for normal controls and 24.4 (20.6–27.6) for women with subclinical hypothyroidism, p=n.s.; frequency of female sexual dysfunction: 68.4% for normal controls vs. 67.4% for women with subclinical hypothyroidism, p=n.s.).

After excluding cases with prior hysterectomy (n=141), the frequency of female sexual dysfunction was significantly different between premenopausal and postmenopausal women (56.7% [302/533] in premenopausal women vs. 80.3% [331/412] in postmenopausal women; p<0.001) In the subgroup analysis according to the menopausal status, the frequency of female sexual dysfunction was not different between normal controls and women with subclinical hypothyroidism, both in premenopausal and postmenopausal women (56.5% for normal controls vs. 58.1% for women with subclinical hypothyroidism, p=n.s. in premenopausal women; 81.0% for normal controls vs. 76.6% for women with subclinical hypothyroidism, p=n.s. in postmenopausal women).

In multiple regression analysis adjusting for confounding variables, subclinical hypothyroidism was also not associated with a risk for female sexual dysfunction (Table 3). In the current study population (middle-aged women), age, menopause status, and low income were the only risk factors for female sexual dysfunction.

Discussion

The primary findings of the study are as follows. First, in middle-aged women, the frequency of subclinical hypothyroidism and female sexual dysfunction were 12.7% and 68.2%, respectively. Second, the total FSFI score and scores in each area were not different between subjects with subclinical hypothyroidism and normal controls. Third, the frequency of female sexual dysfunction was not different between the two groups, and this finding was consistent even after adjusting for confounding variables.

In modern society, people consider a sexual relationship an important part of their life even in their middle-age years. Therefore, sexual dysfunction can have adverse influence on social relationships and self-respect. However, this disorder has been neglected by clinicians and patients despite its importance and relatively high prevalence. In fact, only a small proportion of patients consult their doctor about sexual problems, and they are not being routinely asked about these problems by their physicians (1,2).

Endocrine disorders often negatively affect sexual activity, and sexual dysfunction can be a sign of endocrine disease (12). Investigations on this topic have been gradually reported since the 1950s, but most studies on sexual dysfunction have focused on male sexual dysfunction, particularly erectile dysfunction (20,21). Until now, relatively few studies have reported on the relationship between endocrinopathies and female sexual dysfunction. Hypoandrogenism causes inadequate vaginal receptivity and results in dyspareunia affecting hypothalamic-limbic structures where it evokes perception and pleasure (15). Hyperprolactinemia may lead to a decline in sexual desire and failures in lubrication and orgasm in females via decreased GnRH production (22).

In thyroid disorders, it is believed that excess or deficient thyroid hormone causes psychiatric disturbances, such as irritability, depression, and changes in sexual behavior (12,13). Hypothyroidism can cause lower 5-hydroxytyramine (5-HT) activity with declining libido (23). In addition, elevated TSH may result in hyperprolactinemia followed by decrease sexual activity.

Subclinical hypothyroidism, affecting 4–10% of adults, is more frequently detected in women than men, and it is detected more frequently at older age (6,24,25). Subclinical hypothyroidism has also been reported to be a risk factor for heart failure, coronary heart disease, and dyslipidemia because thyroid hormones are important for the synthesis and metabolism of lipids (26 –30). In addition, several psychosocial disorders may be modulated by subclinical hypothyroidism, such as mood disorders, memory function, and quality of life, although the mechanism underlying these associations is unclear (31). However, few studies have reported on the relationship between subclinical hypothyroidism and female sexual dysfunction. One case series focused on the association between subclinical hypothyroidism and female sexual dysfunction, suggesting that there is no relationship between subclinical hypothyroidism and female sexual dysfunction, conflicting with earlier studies about hypothyroidism and female sexual dysfunction (16). The latter study included relatively young women (M _age=38 years) (16), but the frequency of subclinical hypothyroidism significantly increases around the period of menopause (>50 years old) (5). The results of the current study support the finding that subclinical hypothyroidism is not a risk factor for female sexual dysfunction.

This study has examined the relationship between female sexual dysfunction and subclinical hypothyroidism in middle-aged women, who are at risk for subclinical hypothyroidism and female sexual dysfunction. It shows that subclinical hypothyroidism is not a risk factor for female sexual dysfunction in middle-aged women. In the study population, only age, menopause, and low income were significant risk factors, and this result is consistent with previous studies (4). To the best of the authors' knowledge, this is the first study to evaluate the relationship between female sexual dysfunction and subclinical hypothyroidism in middle-aged women. This information may be used when counseling patients with subclinical hypothyroidism.

The current study did not evaluate the relationship between other hormonal analyses such as prolactin, follicle-stimulating hormone, luteinizing hormone, or estradiol and female sexual dysfunction. In addition, data on thyroid autoantibodies such as thyroglobulin antibody or thyroid peroxidase antibody to determine the possibility of autoimmune diseases are missing in the current study. Further studies on these hormones and autoantibodies are needed to enhance the understanding of the relationship between subclinical hypothyroidism and female sexual dysfunction.

In conclusion, subclinical hypothyroidism is not a risk factor for sexual dysfunction in middle-aged women.