PCOS vs Cushing: Hormonal Differences, Symptoms, and Management

Polycystic ovary syndrome (PCOS) and Cushing’s syndrome are endocrine disorders with overlapping symptoms, often leading to diagnostic challenges. Both involve hormonal imbalances affecting metabolism, reproductive health, and physical appearance. Understanding their distinctions is crucial for accurate diagnosis and effective treatment.

Key Hormonal Differences

PCOS is primarily driven by excess androgens, particularly testosterone, along with insulin and luteinizing hormone (LH) dysregulation. Cushing’s syndrome results from prolonged exposure to elevated cortisol, often due to endogenous overproduction or corticosteroid use. These hormonal differences lead to distinct metabolic and reproductive effects.

In PCOS, increased ovarian androgen production, exacerbated by insulin resistance, leads to hyperandrogenic symptoms such as hirsutism, acne, and scalp hair thinning. Elevated LH relative to follicle-stimulating hormone (FSH) disrupts follicular development, causing anovulation. Insulin resistance further amplifies androgen synthesis by reducing sex hormone-binding globulin (SHBG), increasing free testosterone levels. Studies indicate that women with PCOS often exhibit total testosterone levels above 50 ng/dL, though thresholds vary (Azziz et al., 2016, Journal of Clinical Endocrinology & Metabolism).

Cushing’s syndrome, in contrast, features excessive cortisol secretion, which disrupts the hypothalamic-pituitary-adrenal (HPA) axis. This suppresses gonadotropin-releasing hormone (GnRH) pulsatility, reducing ovarian estrogen production. Unlike PCOS, where androgens originate from the ovaries, Cushing’s syndrome involves adrenal-derived androgens like dehydroepiandrosterone sulfate (DHEA-S). Elevated cortisol also promotes gluconeogenesis and lipolysis, contributing to central adiposity and insulin resistance through different mechanisms than PCOS. A 2021 meta-analysis in The Lancet Diabetes & Endocrinology found that patients with Cushing’s syndrome typically have fasting cortisol levels exceeding 15 µg/dL, with late-night salivary cortisol being a highly sensitive diagnostic marker.

Feedback mechanisms further differentiate these conditions. In PCOS, the hypothalamic-pituitary-ovarian (HPO) axis remains responsive to external modulation, allowing ovulatory function to be restored with targeted interventions. In Cushing’s syndrome, autonomous cortisol production renders the HPA axis resistant to normal regulatory controls, evident in the failure of dexamethasone suppression testing, a hallmark diagnostic feature.

Common Manifestations

Both PCOS and Cushing’s syndrome share symptoms related to reproductive health, metabolism, and dermatological changes. However, the underlying mechanisms differ, influencing diagnosis and management.

Menstrual Irregularities

Both conditions can disrupt menstrual cycles, but with distinct patterns. PCOS typically presents as oligomenorrhea (infrequent periods) or amenorrhea (absence of periods) due to chronic anovulation caused by LH and FSH imbalance. A study in Human Reproduction (2020) found that up to 85% of individuals with PCOS experience irregular cycles.

Cushing’s syndrome disrupts menstruation due to cortisol-induced suppression of GnRH secretion, leading to reduced LH and FSH levels and hypogonadotropic hypogonadism. Unlike PCOS, where estrogen levels are often normal or elevated, Cushing’s syndrome is associated with lower estrogen, resulting in more profound menstrual suppression. A retrospective analysis in The Journal of Clinical Endocrinology & Metabolism (2019) reported that 70% of women with Cushing’s syndrome experience menstrual dysfunction, with amenorrhea being more common in severe cases.

Metabolic Issues

Metabolic disturbances are prominent in both disorders but arise from different mechanisms. PCOS is strongly associated with insulin resistance, increasing the risk of type 2 diabetes. Studies show that even lean individuals with PCOS exhibit reduced insulin sensitivity. A 2021 meta-analysis in Diabetes Care found that women with PCOS have a fourfold higher risk of developing type 2 diabetes.

Cushing’s syndrome induces metabolic dysfunction primarily through cortisol’s effects on glucose metabolism. Excess cortisol promotes hepatic gluconeogenesis and impairs insulin signaling, leading to steroid-induced diabetes. Unlike PCOS, where insulin resistance is often peripheral, Cushing’s syndrome affects multiple pathways, causing central obesity with fat accumulation in the abdomen, supraclavicular region, and face (moon facies). A study in The Lancet Diabetes & Endocrinology (2022) reported that nearly 80% of individuals with Cushing’s syndrome develop glucose intolerance or diabetes.

Skin Changes

PCOS and Cushing’s syndrome share some dermatological symptoms, but distinct features aid differentiation. In PCOS, elevated androgens cause acne, seborrhea, and hirsutism, particularly in androgen-sensitive areas like the face, chest, and back. Hirsutism, assessed using the Ferriman-Gallwey scoring system, affects about 70% of women with PCOS, with severity correlating with free testosterone levels (The British Journal of Dermatology, 2018).

Cushing’s syndrome is marked by skin atrophy, easy bruising, and wide, violaceous striae due to cortisol’s catabolic effects on collagen. These striae are typically wider than those seen in obesity or pregnancy. Facial plethora (redness) and delayed wound healing are also common due to cortisol’s immunosuppressive properties. A 2020 review in The Journal of Investigative Dermatology found that skin thinning and bruising occur in over 60% of patients with Cushing’s syndrome, making these features useful diagnostic indicators.

Diagnostic Evaluations

Differentiating PCOS from Cushing’s syndrome requires clinical assessment, biochemical testing, and imaging. Since both conditions share symptoms like menstrual irregularities, metabolic disturbances, and dermatological changes, precise hormone evaluation is necessary.

A thorough history provides key diagnostic clues. PCOS symptoms often begin in adolescence, with irregular cycles and hyperandrogenism. Cushing’s syndrome typically presents with a more abrupt onset, including rapid weight gain, proximal muscle weakness, and skin changes like easy bruising and wide striae. Progressive worsening over months raises suspicion for hypercortisolism, particularly with facial plethora and supraclavicular fat deposition.

Hormonal testing is crucial. PCOS is characterized by elevated total and free testosterone, increased LH relative to FSH, and hyperinsulinemia, while cortisol levels remain normal. In Cushing’s syndrome, cortisol remains consistently elevated and fails to suppress with dexamethasone, a hallmark feature of autonomous cortisol production. Late-night salivary cortisol and 24-hour urinary free cortisol are highly sensitive diagnostic tools. Plasma adrenocorticotropic hormone (ACTH) levels help distinguish between adrenal and pituitary causes, with suppressed ACTH indicating an adrenal source and elevated ACTH suggesting a pituitary or ectopic origin.

Imaging is necessary when biochemical tests suggest Cushing’s syndrome. CT scans of the adrenal glands identify adrenal adenomas or hyperplasia, while MRI of the pituitary gland detects corticotroph adenomas in Cushing’s disease. Imaging is not routinely required for PCOS, though ovarian ultrasound may assess follicular morphology. The presence of 12 or more antral follicles in one ovary supports a PCOS diagnosis but is not required under the Rotterdam criteria.

Management Options

Treatment strategies must address the underlying hormonal imbalances while mitigating associated health risks. PCOS management focuses on restoring reproductive and metabolic function, while Cushing’s syndrome requires cortisol reduction.

For PCOS, lifestyle modifications, particularly diet and exercise, improve insulin sensitivity and reduce hyperandrogenism. Oral contraceptives regulate menstrual cycles and suppress ovarian androgen production, while anti-androgens like spironolactone address hirsutism and acne. Metformin improves glucose metabolism and ovulatory function, particularly in those with insulin resistance. Ovulation induction agents like letrozole or clomiphene citrate are used for fertility treatment.

Cushing’s syndrome requires direct intervention to reduce cortisol excess. If caused by an adrenal or pituitary tumor, surgical resection is the preferred approach. When surgery is not feasible or only partially effective, medical therapies like ketoconazole, metyrapone, or osilodrostat inhibit cortisol synthesis. Radiation therapy is occasionally used for pituitary-dependent cases when surgery is insufficient.

Potential Complications

Unmanaged PCOS and Cushing’s syndrome can lead to significant long-term health risks. While both conditions share some metabolic and cardiovascular concerns, their complications differ based on underlying pathophysiology.

PCOS increases the risk of type 2 diabetes due to persistent insulin resistance. Chronic anovulation raises the risk of endometrial hyperplasia and carcinoma due to prolonged estrogen exposure. Cardiovascular risks, including dyslipidemia, hypertension, and systemic inflammation, contribute to a higher incidence of coronary artery disease.

Cushing’s syndrome predisposes individuals to osteoporosis and fractures due to cortisol-induced bone resorption and decreased calcium absorption. Hypercortisolism also increases infection susceptibility due to immune suppression, leading to delayed wound healing. Psychological effects, including depression, anxiety, and cognitive impairment, are common. Severe cases can result in life-threatening complications like hypertensive crises, thromboembolic events, and adrenal insufficiency following abrupt cortisol reduction.