A Biopsychosocial View of Polycystic Ovary Syndrome (PCOS)

Running head: A BIOPSYCHOSOCIAL VIEW OF PCOS A Biopsychosocial View of Polycystic Ovary Syndrome (PCOS) Kimberly Osburn Liberty University Online COUN 502-D07 Dr. Robert Grice December 17, 2010 1 A BIOPSYCHOSOCIAL VIEW OF PCOS 2 Abstract Despite the implication of the name, Polycystic Ovary Syndrome (PCOS) affects not merely the ovaries, but endocrine system function, psychological health, psychosocial and psychosexual development throughout the lifespan. Up to 10% of pre-menopausal women meet the diagnostic criteria for PCOS, making it the most prevalent endocrine disorder for this population. Common features of PCOS include: polycystic ovaries, irregular or absent ovulation, disruption of the menstrual cycle, hyperandrogenism, insulin resistance, and central obesity. A review of extant literature reveals that as many as 50% of women with PCOS also meet the diagnostic criteria for a mood or anxiety disorder, with a strong correlation between PCOS and bipolar disorder. While such correlation does not equate to causality, some studies suggest that disruption of the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes might be the common etiology between the physical manifestations of PCOS and the decreased psychological wellbeing experienced by women with PCOS. Hyperandrogenism is a particular source of concern in psychosocial and gender identity development. Some studies show a significantly higher prevalence of PCOS among lesbian women and female-to-male transsexuals compared to the general population, while heterosexual women with PCOS frequently report feeling “different” or “less feminine” due to hyperandrogenism and infertility. Researchers recommend implementing routine screening of women with PCOS for psychological disorders, and conversely, screening of women with mood disorders for reproductive endocrinological dysfunction. A BIOPSYCHOSOCIAL VIEW OF PCOS 3 A Biopsychosocial View of Polycystic Ovary Syndrome (PCOS) Despite the implication of the name, Polycystic Ovary Syndrome (PCOS) affects not merely the ovaries, but endocrine system function, psychological health, psychosocial and psychosexual development throughout the lifespan. Up to 10% of pre-menopausal women meet the diagnostic criteria for PCOS, making it the most prevalent endocrine disorder for this population (Agrawal et al., 2004), and the most frequent cause of female infertility (BidzinskaSpeichert, 2008). Common features of PCOS include: polycystic ovaries, irregular or absent ovulation, disruption of the menstrual cycle, hyperandrogenism, insulin resistance, and central obesity (Coffey, Bano, & Mason, 2006). PCOS may lead to long-term outcomes of coronary heart disease, hypertension, diabetes and cancer (Rasgon, 2001). Studies utilizing psychometric testing have demonstrated that as many as 50% of women with PCOS have significant depression (Rasgon et al., 2003; Himelein & Thatcher, 2006; Ozenli et al., 2009). A similar relationship between PCOS and anxiety has been established (Ozenli et al.; Deeks, Gibson-Helm, & Teed, 2010). Klipstein and Goldberg (2006) found a higher prevalence of bipolar disorder in women with PCOS than would be anticipated in the general population. Women with PCOS report diminished psychological health-related quality of life, with PCOS having “a greater psychological impact than asthma, epilepsy, diabetes, back pain, arthritis and coronary heart disease” (Coffey, Bano, & Mason, 2006, p. 85). Psychosexual development can be profoundly affected, with some women reporting that they feel “freakish”, “abnormal”, and “unfeminine” due to hyperandrogenism and infertility (Kitzinger & Willmott, 2002). Despite these findings, it is uncommon for a woman presenting to a gynecology office for PCOS treatment to be screened for comorbid psychological disorders, and psychosocial concerns A BIOPSYCHOSOCIAL VIEW OF PCOS 4 are essentially left unaddressed (Ozenli et al., 2009). The purpose of this literature review is to synthesize current research on PCOS from a biological, psychological, and social developmental perspective, exploring ways in which more holistic treatment may be provided to women with PCOS. Current trends in developing integrated treatment protocols are discussed, along with identified needs for future research. Biological Effects of PCOS A diagnosis of PCOS requires at least two of the following symptoms: (1) polycystic ovaries observed on ultrasound; (2) oligoovulation or anovulation; and (3) hyperandrogenism, evidenced by elevated serum androgen levels, or clinical presentation of hirsutism, acne vulgaris, and/or alopecia (Bidzinska-Speichert, 2008). Other disorders causing similar symptoms must be excluded before arriving at a diagnosis of PCOS (Bidzinska-Speichert). Additionally, the clinical presentation of PCOS may include disruption of the menstrual cycle, infertility, skin tags, acanthosis nigricans (patches of dark, thickened skin), and visceral abdominal obesity (Stephenson & Stewart, 2010). PCOS is associated with insulin resistance and chronic low-grade inflammation (Benson et al., 2008), creating an increased long-term risk of obesity, coronary heart disease, hypertension, and diabetes (Rasgon, 2001), while amennorhea increases the risk of endometrial cancer (Agrawal et al., 2004). While the etiology of PCOS remains unclear, Rasgon (2001) proposed that dysfunction of the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes may be causative factors. Figures 1 and 2 illustrate the HPA and HPG systems, respectively. The hypothalamus, pituitary gland, adrenal gland, ovaries, thyroid gland and pancreas each secrete specific hormones in a continual feedback loop, stimulating one another to produce hormones (Hiller-Sturmhofel & Bartke, 1998). A disruption at any point in the feedback loop can create A BIOPSYCHOSOCIAL VIEW OF PCOS 5 serious medical problems (Hiller-Sturmhofel & Bartke). Figure 3 demonstrates the disruptions that occur in PCOS. Figure 1 – The HPA Axis (Hiller-Sturmhofel & Bartke, 1998) Figure 2 – The female HPG Axis (Hiller-Sturmhofel & Bartke) Figure 3 – Pathophysiology of PCOS (Rasgon et al., 2002) A BIOPSYCHOSOCIAL VIEW OF PCOS 6 Biopsychological Connection Between PCOS, Mood and Anxiety Disorders Studies utilizing psychometric testing have demonstrated that as many as 50% of women with PCOS have significant depression (Rasgon et al., 2003; Himelein & Thatcher, 2006; Ozenli et al., 2009; Mansson et al., 2008). A similar relationship between PCOS and anxiety has been established (Ozenli et al.; Deeks, Gibson-Helm, and Teed, 2010). Mansson et al. expanded on previous research findings that women with PCOS have greater self-reported levels of depression and anxiety compared with control groups. The MINI International Neuropsychiatric Interview was administered to 49 women with PCOS and 49 matched controls to screen for Axis I psychiatric disorders. Participants were also tested for serum androgen levels. Women in the PCOS group were more likely to have experienced at least one major depressive episode, social phobia, and/or any eating disorder. They were also 7 times more likely to have attempted suicide at least once. Additionally, they were more likely to have used antidepressant and/or anxiolytic drugs. Due to the striking findings regarding suicidality, the authors emphasize the need to thoroughly screen women with PCOS for psychiatric disorders. Klipstein and Goldberg (2006) explored the hypothesis that PCOS and bipolar disorder share a common etiology. Although only 7.7% of study participants reported having a previous diagnosis of bipolar disorder, 24.4% screened positive for bipolar spectrum disorders on the Mood Disorders Questionnaire (MDQ) – a rate much higher than would be anticipated in the general population. Conversely, there is a higher prevalence of PCOS in women with bipolar disorder (Jiang, Kenna, & Rasgon, 2009). Although this connection was previously attributed to the effects of antiepileptic drugs (e.g. valproate) on endocrine function, only 4% of participants in the Klipstein and Goldberg (2006) study were exposed to valproate prior to being diagnosed with PCOS, suggesting that PCOS and bipolar disorder may share a common etiology. Joffe et A BIOPSYCHOSOCIAL VIEW OF PCOS 7 al. (2006, as cited in Joffe, 2007) also found a higher prevalence of preexisting menstrual dysfunction in women with bipolar disorder and unipolar depression than healthy controls. While such correlation does not equate to causality, Rasgon (2001) proposed that disruption of the HPG and HPA axes might be the common etiology between the physical manifestations of PCOS and the decreased psychological wellbeing experienced by women with PCOS. Young (2004) described the prominent role excess cortisol secretion in the HPA axis plays in exacerbating depression. In a study of stress responses in women with PCOS, Benson et al. (2009) noted significantly higher increases in cortisol levels in the PCOS group compared with controls. The chronically elevated cortisol levels common to both PCOS and mood disorders cause insulin resistance, leading to impaired glucose tolerance and visceral obesity (Jiang, Kenna, & Rasgon, 2009). This in turn can affect the HPG axis, leading to anovulation and hyperandrogenism (Rasgon, 2001). Women with PCOS report diminished psychological health-related quality of life, with PCOS having “a greater psychological impact than asthma, epilepsy, diabetes, back pain, arthritis and coronary heart disease” (Coffey, Bano, & Mason, 2006, p. 85). Coffey et al. surveyed 22 women diagnosed with PCOS and 96 randomly selected women from the general population using the 36-item Short-Form Health Survey (SF-36) and the Polycystic Ovary Syndrome Questionnaire (PCOS-Q). The purpose was to measure the health-related quality of life (HRQoL) of a cross-section of women with PCOS to that of a cross-section of women in the general population. The SF-36 data of both groups were also compared to SF-36 data previously gathered for Oxford Health and Lifestyle Survey (OHLS), a survey of the general population in Oxford, U.K, for the purpose of comparing PCOS to previously-obtained data about HRQoL in persons with other chronic illnesses. Based on an analysis of the data, the authors concluded that A BIOPSYCHOSOCIAL VIEW OF PCOS 8 women with PCOS demonstrate significantly lower psychological HRQoL compared with the control group, and with all other illnesses in the OHLS data. Psychosocial and Psychosexual Concerns De Niet et al. (2010) assessed 480 women with PCOS utilizing the following self-report Likert scale assessments: Rosenberg self-esteem scale (RSES), body cathexis scale (BCS), fear of negative appearance evaluation scale (FNAES), and a 2-question assessment of sexarche. Results were compared to norm scores of control groups from previous studies cited in the article. Women with PCOS reported lower self-esteem and body satisfaction compared to control norm scores; however, these differences were very small. Within the study group, amenorrhea was associated with reduced self-esteem, greater fear of negative appearance evaluation, and earlier sexarche compared to women with oligomenorrhea (De Niet et al., 2010). Hyperandrogenism was associated with reduced body satisfaction compared to women with normal androgen levels. Women with hirsutism scored lower on all three measures compared with non-hirsute women. Higher BMI was also associated with lower scores on all three measures. The authors acknowledge the limitations of this study, including the lack of a matched sample group and the possible influences of culture and ethnicity. Kitzinger and Willmott (2002) conducted a qualitative study of 30 women with PCOS to learn more about women’s individual perspectives on their experiences of PCOS. Participants were recruited through the British PCOS self-help group Verity. Interviews were structured with open-ended questions, allowing each woman the opportunity to tell her story of how she was diagnosed with PCOS, how she dealt with the symptoms she experienced, and how she feels about having the syndrome. Interviews were tape recorded for later transcription. Rather than A BIOPSYCHOSOCIAL VIEW OF PCOS 9 analyzing the transcriptions for quantifiable data, responses were examined in search of recurrent themes, which included nearly unanimous reports of feeling “freakish, abnormal… and less feminine” (p. 349) due to the physical effects of the syndrome. Specifically, women felt that the absence of regular menses, infertility, and hirsutism greatly diminished their sense of womanhood. Women expressed exhaustion with the great lengths to which they must go to remain free of unwanted facial and body hair in order to look like a “normal” woman (p. 354). Discussing the interview results from a feminist perspective, Kitzinger and Willmott (2002) propose that societal images of femininity are unrealistic and nearly impossible to attain, even without the challenges of PCOS. Furthermore, the authors discuss the emphasis in feminist writings on menstruation and fertility as being hallmarks of feminine identity, and the cultural pressure this creates for women with PCOS who are unable to conform to these ideals. Manlove, Guillermo, and Gray (2008) hypothesized that hyperandrogenism associated with PCOS might cause less gender-typical behavior in this population. The study compared the self-reported gender-typed behavior of 34 women with a self-reported diagnosis of PCOS with 27 women with no PCOS diagnosis. Overall, the PCOS group reported less typical feminine behavior in childhood. In adolescence, differences were primarily psychosocial concerns; although the PCOS group did not behave in less feminine ways, they felt less socially accepted. Gender-typical behavior also was not significantly different in adulthood, although there was a higher prevalence of bisexualism and a greater tendency to have changed sexual orientation during the lifespan in the PCOS group. Agrawal et al. (2004), practicing physicians in reproductive medicine, noticed anecdotally over time that a high percentage of women who self-identified as having a lesbian sexual orientation had either polycystic ovaries (PCO) or met the full diagnostic criteria for A BIOPSYCHOSOCIAL VIEW OF PCOS 10 PCOS. The authors launched a prospective observational study of 618 women presenting to the two clinics for infertility treatment, including 254 lesbian women and 364 heterosexual women. Based on pelvic ultrasound examinations and serum androgen concentrations, the authors determined that 80% of the lesbian women had PCO and 38% had PCOS, compared with 32% and 14% of heterosexual women, respectively. Of women with either PCO or PCOS, the lesbian women had higher serum androgen levels. This study was the first to investigate the prevalence of PCO or PCOS in lesbian women, and remains one of only two such studies in the literature. The second study, conducted by De Sutter et al. (2008), did not replicate these findings. As Agrawal et al. (2004) are careful to point out, it would be premature to conclude that PCO, PCOS, and/or hyperandrogenism are causative factors in sexual orientation. Notably, 32% of the heterosexual women also had PCO, while 20% of the lesbian women did not. It should also be clarified that the population studied had all presented for infertility treatment, and thus is not necessarily reflective of the general population who identify as lesbian. However, the possible existence of a correlation between lesbian sexual orientation and a serious medical condition such as PCOS is important to identify so that effective screening and treatment in this population may take place. Some studies have identified a higher prevalence of PCOS in female-to-male (FTM) transsexuals prior to initiating androgenic treatment (Baba et al., 2007; Vujovic, Popovic, Sbutega-Milosevic, Djordjevic, and Gooren, 2009). Vujovic et al. point out that while hormonal factors are not sole determinants in gender identity, they may play an influential role. Baba et al. emphasized the importance of clinicians remaining mindful of the serious health risks associated with administering androgenic therapy to FTM transsexual patients. A BIOPSYCHOSOCIAL VIEW OF PCOS 11 The Grief of Infertility and Miscarriage According to Teede, Deeks, & Moran (2010), approximately 40% of women with PCOS experience infertility. In addition to the self-perception of being “different” because of infertility (Kitzinger and Willmott, 2002, p. 349), women often experience grief and loss for the child they may never have. According to Smith and Smith (2004), the emotional process that women with infertility go through coincides with Kubler-Ross’s renowned stages of grief: 1. Denial – disbelief that infertility exists 2. Anger – at oneself for not being able to conceive, at other women who are able to conceive, or at God for not allowing conception to take place 3. Bargaining – subjecting oneself to all kinds of infertility treatments in desperation 4. Depression – a sense of helplessness and hopelessness over the situation 5. Acceptance – coming to terms with the reality of childlessness The sense of helplessness and hopelessness expressed by many infertile women may be of particular importance. In a study by Ozenli et al. (2009), helplessness and self-blaming, along with an unwilling, resigned acceptance of one’s situation, were correlated with higher levels of anxiety and depression among women with PCOS. People with chronic illness who employ such emotion-focused problem-solving techniques tend to have poorer long-term outcomes (Ozenli et al.). Deeks, Gibson-Helm, and Teed (2010) found that women with PCOS who were also infertile were more likely to meet clinical diagnostic criteria for depression and anxiety than women with PCOS who were not infertile. Infertility has a profound psychosocial effect on marital/partner relationships. The physical challenges and psychological stress of infertility treatments puts tremendous strain on relationships (Smith & Smith, 2004). The experience of sexual intercourse that was once a A BIOPSYCHOSOCIAL VIEW OF PCOS 12 symbol of shared intimacy can become mechanical under the stress of trying to conceive within a particular ovulation window (Smith & Smith). Couples surveyed by Smith & Smith reported considerable feelings of ambivalence and emotional conflict surrounding the celebration of events such as Mother’s Day, Father’s Day, baby showers, and religious child dedication ceremonies. Couples from a Judeo/Christian background may have developed the notion that childlessness is a curse from God, based on scripture passages portraying infertility in a negative light, increasing feelings of shame and anger. While not all women with PCOS experience infertility, achieving pregnancy itself carries significant risks. The miscarriage rate for women with PCOS ranges from 30-50% (Khattab et al., 2006). Women with PCOS may experience recurrent miscarriages, compounding their sense of grief and loss (Khattab et al.). Obesity and insulin resistance exacerbate the risk of miscarriage (Teede, Deeks, & Moran, 2010). Holistic Treatment of PCOS Although there is no cure for PCOS, the myriad of treatment options can be daunting. The focus of treatment depends on the symptom manifestations and current life stage of each patient. Reducing the long-term health risks of obesity, insulin resistance, and endometrial cancer are of primary concern. Lifestyle changes including a low-fat diet and exercise program can be substantially beneficial; even a 5-10% weight loss may restore normal ovulatory function, increase insulin sensitivity, and improve psychological well-being (Teede, Deeks, & Moran, 2010). While Teede et al. recommend a high-carbohydrate, low-fat, moderate protein diet, Galletly et al. (2007) compared the psychological effects of a high-protein, low-carbohydrate (HPLC) diet with those of a low-protein, high-carbohydrate (LPHC) diet. Both diets were low in fat. As measured by the Hospital Anxiety and Depression Rating Scale (HAD) and the A BIOPSYCHOSOCIAL VIEW OF PCOS 13 Rosenberg Self Esteem Rating Scale rating scale (SE), the HPLC group experienced significant improvement in depression and self-esteem, while the LPHC group had no improvement. Weight loss in both groups was comparable. Further research is needed to determine whether the mood elevations were a result of components of the food selections themselves, of the greater satiety generally associated with higher protein consumption, or other factors. When lifestyle modifications alone are not effective, insulin-sensitizing drugs such as metformin and pioglitazone (Actos) are typically the first-line drug treatment for PCOS, as they have demonstrated efficacy in restoring ovulation and regular menstruation, reducing androgen secretion, and improving glucose tolerance (Katsiki, Georgiadou, & Hatzitolios, 2009). For women who want to conceive, metformin is often effective in inducing ovulation, either alone or in combination with clomifene (Katsiki et al.). Gastrointestinal side effects of metformin can inhibit treatment compliance (Khattab et al., 2006). Khattab et al. (2006) demonstrated the effectiveness of metformin in reducing the rate of first-trimester miscarriages for pregnant women with PCOS. All of the 200 participants took metformin while trying to conceive. After conception, 120 continued metformin therapy while 80 discontinued the drug (the control group). The rate of miscarriage in the first trimester was 11.6% for the metformin treatment group, compared to 36.3% for the control group. The researchers concluded that the insulin-sensitizing, antiandrogenic, and anti-inflammatory effects of metformin have a protective effect on the developing fetus. For women who do not currently wish to conceive, low-dose oral contraceptive pills (OCPs) can be used to regulate the menstrual cycle, reducing the risk of endometrial cancer (Teede et al., 2010). OCPs are also effective in reducing androgen secretion, which may ameliorate the cosmetic effects of hyperandrogenism. Teede et al. recommend a minimum 6- A BIOPSYCHOSOCIAL VIEW OF PCOS 14 month trial of OCPs to reduce hyperandrogenism; if this is not effective, antiandrogenic drugs such as spironolactone or cyproterone acetate may be introduced. The decreased androgen levels brought about by spironolactone bring about improved insulin sensitivity (Rasgon et al., 2002). Rasgon et al. have speculated that antiandrogenic and antiglucocorticoid drugs might also have an antidepressant effect by reducing the secretion of androgens and cortisol while improving insulin resistance, particularly when administered along with insulin-sensitizing medications such as metformin. Further research is needed to validate this assumption. While the cosmetic concerns of hyperandrogenism are a significant psychosocial factor, antiandrogenic drugs must only be used concurrently with birth control due to teratogenic effects (Teede et al., 2010). This substantially limits treatment options for women who are trying to conceive, or choose not to use birth control for other reasons. Professional cosmetic treatments for hirsutism include waxing, electrolysis, or laser hair removal. Such treatments can be costly, and are generally not covered by medical insurance because they are not deemed medically necessary. Clayton, Lipton, Elford, Rustin, and Sherr (2005) conducted a randomized controlled trial of laser hair removal vs. non-removal on 88 women with facial hirsutism due to PCOS. Over a period of 6 months the non-removal (control) group were led to believe they were receiving laser hair removal treatment, but in reality were receiving virtually ineffective low fluence laser treatment, while the intervention group received standard high fluence laser treatment. Although no one was charged for the treatments, at the end of the study the control group members were offered 6 months of free treatment to compensate for the necessary deception of the study. Self-report measures were used to quantify severity of facial hair, daily time spent on hair removal, depression, anxiety, and quality of life. All measures improved A BIOPSYCHOSOCIAL VIEW OF PCOS 15 significantly more in the intervention group than the control group, suggesting that laser hair removal improves health-related quality of life for women with PCOS. Although the results of the Clayton et al. (2005) study seem to indicate that laser treatment of hirsutism in women with PCOS substantially improves psychological wellbeing, the potential conflicts of interest in this study are notable. Two of the authors operate a private hair removal practice; thus, the authors have a vested interest in proving that such treatments improve psychological health to obtain funding for future clientele. Nevertheless, considering the abundance of studies demonstrating the negative effect of hirsutism on quality of life, the authors’ assertion is plausible. Treating Comorbid Psychological Disorders In recent years, researchers have recommended routine screening of women with PCOS for DSM-IV mood and anxiety disorders (Hollinrake, Abreu, Maifeld, Van Voorhis, & Dokras, 2007; Mansson et al., 2008; Klipstein & Goldberg, 2006). The Polycystic Ovary Syndrome Questionnaire (PCOSQ) has demonstrated reliability and validity for measuring psychological concerns specific to PCOS (Coffey, Bano, & Mason, 2006). Additional psychometric measures include the Beck Depression Inventory (BDI), the Spielberger State-Trait-Anxiety Inventory (STAI-S), and the Ways of Coping Inventory (WCI) (Ozenli et al., 2009; Benson et al., 2009). Klipstein and Goldberg (2006) recommend using the Mood Disorders Questionnaire (MDQ) to screen for lifetime manic or hypomanic symptoms. Because of the correlation between bipolar disorder and PCOS, it is important for mental health professionals to be alert to clinically relevant signs of PCOS such as hyperandrogenism, menstrual irregularity, or central obesity (Joffe, 2007). In addition to the prevalence of preexisting menstrual dysfunction in women with bipolar disorder, antiepileptic and A BIOPSYCHOSOCIAL VIEW OF PCOS 16 antipsychotic drugs used for treatment of bipolar disorder can alter hormone levels, causing symptoms of PCOS (Joffe). This is an essential treatment consideration because of the multiple long-term health risks. Mental health clinicians must exercise caution in treating women of reproductive age for bipolar disorder (Joffe). Addressing Psychosocial Concerns Interventions commonly used to address general psychosocial concerns are useful for women with PCOS. Rofey et al. (2009) evaluated an 8-week group Cognitive Behavioral Therapy (CBT) intervention for adolescents with PCOS and obesity. Participants lost a significant amount of weight and scored lower on the Children’s Depression Inventory by the end of the 8-week session. Participants in a nurse-led peer support group felt less isolated and more empowered to cope with their illness (Percy, Gibbs, Potter, & Boardman, 2009). Ozenli et al. (2009) recommend individual psychotherapy to help women with PCOS develop more active, problem-focused ways of coping. Cognitive-based couples therapy can help couples work through the grief and emotional trauma of infertility, employing cognitive restructuring techniques to help couples change their perspective on childlessness (Smith & Smith, 2004). Supportive individual therapy may also be helpful for women dealing with concerns about gender identity or sexual orientation. 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