DMEJ

   Duke Medical Ethics Journal   

The Potential of Precision Medicine in the Preventive Care of Polycystic Ovarian Syndrome

By: Shernice Martin

Polycystic Ovarian Syndrome, more commonly referred to as PCOS, is the most common endocrinopathy comprising women’s health challenges today. 1 in 10 women of reproductive age experience PCOS (USDHHS, 2014). Symptoms begin in adolescence, typically after the patient’s first period; they can include metabolic dysfunction, menstrual cycle changes, increased facial and body hair and acne, cysts in the ovaries, and, ultimately, infertility. However, many patients remain undiagnosed until they begin to have fertility issues (NICHD, 2019). 

A diagnosis of PCOS only follows an examination of the Rotterdam criteria, which states  the main diagnostic factors for PCOS as the presence of ovarian cysts, menstrual irregularities, high androgen levels, and obesity (PCOS Consensus Workshop Group, 2004). Once diagnosed, many contemporary clinical innovations and therapies are used in the treatment, management, and reversal of PCOS symptoms. However, if similar innovations could be used to diagnose PCOS earlier in the lifespan, preventive care could be implemented to mitigate the negative consequences on reproductive health and holistic wellbeing later in life. Precision medicine–  the clinical approach that considers individual differences in genetics, environments, and lifestyles— could play a significant role in this (Center for Devices and Radiological Health, 2018).

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Currently, diagnosis and treatment of PCOS is subject to variable diagnostic criteria, inconsistent provider knowledge, and failure to arrive at a consensus which poses major challenges (Witchel et. al., 2018). Given the accurate and discrete data yielded by analytic precision medicine techniques, diagnosis can become easily quantifiable while retaining the flexibility that accounts for differences among patients. In this way, provider knowledge about the illness and how to treat it will become more homogenous, and a systematic mechanism of treatment will be established. If implemented correctly, the rate of identification of “at-risk” individuals would increase at an earlier age and preventive care could be employed as a feasible intervention. Patients who have already been diagnosed would have more comprehensive and effective primary care to mitigate symptoms. Within each of these domains, the ethical challenges of implementation must be considered to support effectiveness for both patients and providers.

"Currently, diagnosis and treatment of PCOS is subject to variable diagnostic criteria, inconsistent provider knowledge, and failure to arrive at a consensus which poses major challenges"

The etiology of PCOS is quite diverse and comprises a plethora of genetic and environmental factors. The condition has been proven to be moderately heritable due to the number of gene mutations that are implicated in its development: namely, proteins involved in the secretion and action of insulin, gonadotropin, and androgen (Ehrmann, 2005). While it has been considered a more dominant ovarian and hormonal disorder, research has more recently expanded this perspective to include metabolic dysfunction (Guo et. al., 2016).  This comes with  the emergence of studies that have supported a correlation between the etiology of PCOS and gut microbiota (Tremellen et. al., 2012; Liu et. al, 2017; Yurtdaş & Akdevelioğlu, 2020).). It is therefore noted that the multifactorial nature of the syndrome spans ovarian, hormonal, and metabolic physiological deficiencies that may bear a close resemblance to other disorders. This can easily become quite complicated,  making it difficult for doctors to detect the development of PCOS, identify at-risk females, and provide effective preventive care. 

There have been implementations to advance preventive care for PCOS within this decade. Researchers have been emphasizing the continued screening of all reproductive-aged women and adolescents for metabolic abnormalities including insulin resistance, as well as hormonal abnormalities such as excess androgen and lack of ovulation. Insulin-sensitizing agents should be prescribed for women who wish to conceive and oral contraceptives for those who do not (Ahles, 2000). While preventive care approaches do hold some importance, they also leave significant room for improvement.

Because the common physiological signs that are screened for PCOS are also implicated in many other metabolic, ovarian, and endocrine conditions, they may not be the most accurate predictors of the condition for all patients. It has been proven that some women experience no PCOS symptoms and can only be diagnosed with ultrasound ovarian imaging (Hassan & Killick, 2001). Additionally, insulin-sensitizing agents and oral contraceptives welcome a plethora of side effects for women and may further exacerbate symptoms without addressing their root causes (Luque-Ramírez et. al., 2020; Nestler et. al., 2003). These medications, which may be helpful with symptom management to an extent, have the potential to do more than harm than good as long-term preventive solutions.

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However, precision medicine can be a pivotal resource that helps physicians to simplify this process and see an overall reduction in the incidence of the disease. One example is the detection of specific PCOS biomarker genes in childhood or pre-adolescence. This can allow young girls to receive the necessary therapeutic interventions prior to puberty onset (when the condition is known to frequently develop) and as such, curb its development. Genetic testing to identify biomarkers can also be used to guide the prescription of medication that can help the body compensate for dysfunctions brought on by protein mutations. If implemented correctly, dysfunction can be corrected, or loss of function restored, specifically with regards to androgen, gonadotropin, and insulin secretion and function. PCOS symptoms will have a much lower probability of being developed given that the body would have been allowed to correct the physiological deficiencies that could influence its development.

Polycystic Ovarian Syndrome, more commonly referred to as PCOS, is the most common endocrinopathy comprising women’s health challenges today. 1 in 10 women of reproductive age experience PCOS (USDHHS, 2014). Symptoms begin in adolescence, typically after the patient’s first period; they can include metabolic dysfunction, menstrual cycle changes, increased facial and body hair and acne, cysts in the ovaries, and, ultimately, infertility. However, many patients remain undiagnosed until they begin to have fertility issues (NICHD, 2019). 

Though the premise of using precision medicine in the context of preventive care appears promising, it is always worthwhile to ethically consider its impact on both the patients and providers. The implementation of genetic biomarker testing is expensive and has differential coverage within the context of preventive care for different health concerns. This raises a fundamental consideration of the principle of justice. The accessibility and equity of these services are low, especially regarding female minority demographics who are already at a higher risk for poor reproductive health outcomes (Landry et. al., 2018). Additionally, the precision medicine approach to preventive care for PCOS relies extensively on genetic testing, which makes use of biopsy and blood testing procedures. Performing these procedures on pre-pubescent females on a regular basis may be traumatic and painful within this sensitive age of development, thereby violating the principle of nonmaleficence. 

In summary, precision medicine can be a powerful tool that changes the trajectory of preventive care for common health issues, specifically Polycystic Ovarian Syndrome. It can help to streamline the identification of at-risk patients and provide individualized care that facilitates the most effective outcome for the patient. However, it must be implemented, like all medical practices, within a framework that prioritizes autonomy, beneficence, nonmaleficence, and justice. It is only when this has been accomplished that it will be a powerful tool,  but also a profitable tool for all.

Review Editor: Olivia Ares
Design Editor: AJ Kochuba
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