Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age, characterized by hormonal imbalances and metabolic changes. The syndrome is frequently associated with an excess of male hormones, known as androgens, which often leads to the assumption that high testosterone is a requirement for diagnosis. However, it is entirely possible to receive a diagnosis of PCOS even when total and free testosterone levels in the blood are within the normal reference range. The medical criteria for identifying the syndrome are broad, recognizing that the condition manifests differently among individuals. A woman can have the full syndrome without elevated testosterone, especially when other diagnostic features are present.
Understanding the Diagnostic Requirements for PCOS
The diagnosis of PCOS relies on the standardized Rotterdam criteria, established by medical consensus in 2003. A diagnosis is made when a woman exhibits at least two out of three specific conditions, after excluding other disorders that might cause similar symptoms. These three conditions are oligo- or anovulation, evidence of hyperandrogenism, and the presence of polycystic ovarian morphology on ultrasound imaging.
Oligo- or anovulation refers to a disruption of the menstrual cycle, typically presenting as infrequent or absent periods, indicating the ovaries are not regularly releasing an egg. Hyperandrogenism is defined as an excess of androgens, identified either by visible physical signs or by elevated hormone levels in blood tests.
The final criterion is the appearance of polycystic ovaries, detected during a transvaginal ultrasound. This morphology is defined by the presence of numerous small follicles (12 or more, measuring two to nine millimeters) or an increased ovarian volume greater than 10 milliliters. Since only two of these three conditions are needed, a woman can meet the diagnostic threshold by having irregular periods and polycystic ovaries, regardless of her androgen status.
Why Testosterone Levels Alone Do Not Rule Out PCOS
Testosterone is only one component used to assess hyperandrogenism, and normal levels do not automatically exclude a PCOS diagnosis. Hyperandrogenism is divided into clinical and biochemical categories. Clinical hyperandrogenism is diagnosed based on physical signs like hirsutism (the growth of coarse, dark hair in a male-typical pattern), severe acne, or androgenic alopecia (male-pattern hair thinning).
These clinical signs alone can be sufficient to meet the hyperandrogenism criterion, even if blood tests for total and free testosterone are normal. This is because the sensitivity of hair follicles and skin to androgens varies greatly among women. A woman may have heightened sensitivity to androgens within the normal range, leading to observable symptoms like hirsutism, which is a valid diagnostic feature.
Furthermore, testosterone is not the only androgen that can be elevated in PCOS. Other androgens, such as androstenedione or dehydroepiandrosterone sulfate (DHEA-S), might be elevated, fulfilling the criteria for biochemical hyperandrogenism even if testosterone itself is normal. These other hormones are precursors to testosterone, and their elevation indicates the underlying hormonal dysfunction characteristic of the syndrome.
This concept is formalized by the recognition of different PCOS “phenotypes,” or presentations. One is the non-hyperandrogenic phenotype (Phenotype D), which involves oligo- or anovulation combined with polycystic ovarian morphology, but with no clinical or biochemical signs of androgen excess. This non-hyperandrogenic phenotype is a recognized and valid diagnosis of PCOS, proving that elevated testosterone is not a prerequisite for the condition.
Treatment Approaches Based on Primary Symptoms
Once a PCOS diagnosis is established, treatment is highly individualized, focusing on managing the patient’s most concerning symptoms rather than normalizing all hormone levels. Management for a woman with normal testosterone levels is tailored to her specific presentation, such as menstrual irregularities or metabolic issues. Lifestyle changes, including dietary modifications and regular exercise, form the first line of management, irrespective of androgen status, due to the underlying link to insulin resistance.
For women whose primary concern is irregular or absent menstrual cycles, hormonal contraceptives are frequently prescribed to regulate the cycle. These medications help prevent endometrial hyperplasia, a condition where the uterine lining thickens due to unopposed estrogen exposure, which increases the risk of endometrial cancer. Alternatively, cyclical progesterone therapy may be used to induce a regular withdrawal bleed and protect the uterine lining.
If metabolic issues, such as insulin resistance, are prominent, medications like metformin may be introduced to improve the body’s response to insulin. Metformin helps regulate blood sugar, and for some women, it may also lead to a more regular menstrual cycle. When infertility is the main issue, regardless of testosterone levels, treatments focus on inducing ovulation using agents such as clomiphene citrate or letrozole. These medications stimulate the release of an egg, improving the chances of conception.