New research suggests three distinct clinical phenotypes enabling us to tailor PCOS treatments to the individual's phenotypic expression and PCOS symptoms.
what is PCOS
Polycystic ovary syndrome (PCOS) is a common but poorly defined heterogeneous condition, affecting 1 in 10 women of reproductive age. It's a hormonal disorder with diverse symptoms and it's the most common cause of menstrual irregularity and infertility.
The current diagnosis is based on the Rotterdam criteria, which requires the presence of at least two out of three features:
Hyperandrogenism (excess male sex hormones)
Ovulatory dysfunction
Polycystic ovarian morphology (i.e. cysts on the ovaries)
To date, the management of PCOS has been based on four phenotypes (see below). However, there has been an ongoing lack of clarity on whether these four phenotypes represent a broad spectrum of the same condition, PCOS. For instance, besides the excess androgens, menstrual irregularities and polycystic ovaries, we also know that insulin resistance, obesity, hirsutism and acne are common features. However, not all women with PCOS exhibit the same symptoms which leads to questions regarding the underlying causes, and therefore treatment strategies.
Established in 2012 non-clinical phenotypes:
A: Hyperandrogenism + ovulatory dysfunction + polycystic ovaries
B: Hyperandrogenism + ovulatory dysfunction
C: Hyperandrogenism + polycystic ovaries
D: Ovulatory dysfunction + polycystic ovaries
The study examined in this article fills a gap in the research regarding PCOS phenotype classification, it is the first cross-sectional study to identify distinct phenotypic expressions of the syndrome. It gives us confidence in understanding the underlying causes of each phenotype, and more research leveraging this study will help bring yet more and more clarity to this syndrome.
PCOS Phenotypes
The study identified three distinct clinical phenotypes of PCOS by analysing hormonal, biochemical and anthropometric measures in a cross-sectional cohort of 520 women with the condition.
A. Ovarian Hyperandrogenism: Neuroendocrine dysfunction + Oligo/Amenorrhea
B. Metabolic Hyperandrogenism: No neuroendocrine dysfunction + Oligo/Amenorrhea
C. Adrenal Hyperandrogenism: No neuroendocrine dysfunction + Regular cycles
PCOS Features and Symptoms
The study suggests that there are three phenotypes driven by either the ovaries, insulin resistance or the adrenals. Each type has distinct features in terms of hormonal profile, biochemical pathway and symptoms.
Ovarian Hyperandrogenism
Phenotype A is dominated by excess steroid hormones from the ovaries leading to dysfunction of the neuroendocrine system.
Neuroendocrine Dysfunction: Excess LH and high LH/FSH ratio
Hormonal Levels: Elevated A4, T, FAI, E2, and 17αOHPG
Biochemical Pathways: Increased 3β-HSD activity leading to increased ovarian E2
Symptoms: Irregular cycles, infertility, potential for increased risk of miscarriage
Metabolic Hyperandrogenism
Phenotype B is dominated by metabolic disturbances, mainly caused by insulin resistance leading to endocrine dysfunction and increased potential of obesity.
Metabolic Dysfunction: Insulin resistance
Hormonal Levels: Elevated DHEAS & A4
Biochemical Pathways: Decreased 3β-HSD activity leading to decreased ovarian E2
Symptoms: Irregular cycles, obesity, acanthosis nigricans (skin condition), and potential for hirsutism
Adrenal Hyperandrogenism
Phenotype C is dominated by excess adrenal steroids mainly caused by elevated levels of DHEAS leading to endocrine dysfunction
Adrenal dysfunction: Excess DHEAS
Hormonal Levels: Elevated P4, high P4 to E2 molar ratio, and high DHEAS levels
Biochemical Pathway: Decrease in 3β-HSD from the ovaries results in adrenal glands producing excess DHEAS
Symptoms: Regular cycles, acne, hirsutism, and relative insulin sensitivity
PCOS Treatments
The suggestion of these three distinct clinical phenotypes in PCOS could potentially revolutionise our approach to treatment. By recognising that each phenotype has unique underlying mechanisms and symptom presentations, it's evident that a generalised treatment strategy is not going to be effective.
For women with Ovarian Hyperandrogenism (Phenotype A), treatments might focus on regulating the neuroendocrine system, perhaps through hormonal therapies that address the excess of steroid hormones from the ovaries.
In contrast, those with Metabolic Hyperandrogenism (Phenotype B) could benefit from interventions targeting insulin resistance, lifestyle modifications, or specific diets that stabilise blood sugar levels. This phenotype would also be more susceptible to type 2 diabetes and addressing obesity can be pivotal in symptom management.
For Adrenal Hyperandrogenism (Phenotype C), treatments might prioritise managing elevated adrenal steroids. This could involve therapies that modulate adrenal function or address the specific symptoms of acne and hirsutism.
Furthermore, with the knowledge of one's specific phenotype, women can explore complementary therapies. These might include specific nutritional supplements, exercise regimens tailored to their phenotype, or even stress-reduction techniques, given the intricate relationship between stress and hormone levels.
In essence, understanding one's PCOS phenotype is not just about categorisation, it's about empowerment. It provides women with the tools to collaborate closely with their healthcare team, ensuring that treatments are not just generalised but are tailored, nuanced, and most importantly, effective.
Reference: pubmed.ncbi.nlm.nih.gov/37217826
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