Androgen Excess in PCOS: Latest Research

Q: What are the PCOS subtypes discussed in the article, and how do they impact treatment options?

The article discusses three primary PCOS subtypes: insulin-resistant , inflammatory , and hyperandrogenic . Each type calls for a distinct treatment approach. For instance, insulin-resistant PCOS is commonly addressed with medications that improve insulin sensitivity, while hyperandrogenic PCOS may involve treatments to lower excess androgen levels, such as hormonal therapies or topical solutions. Understanding which subtype you have is crucial for developing a treatment plan that works best for you.

Androgen excess affects up to 80% of women with PCOS and is a key factor behind symptoms like unwanted hair growth, acne, and hair loss. It also contributes to fertility challenges, insulin resistance, and long-term health risks like type 2 diabetes and cardiovascular disease. Understanding the hormonal and metabolic causes of androgen excess is crucial for effective management.

Key Points:

Main Cause: Hormonal imbalances and insulin resistance drive androgen overproduction in PCOS.
Symptoms: Hirsutism, acne, androgenic alopecia, irregular periods, and ovulation issues.
Health Risks: Infertility, metabolic syndrome, and cardiovascular complications.
Treatment Options:
- Medications: Insulin-sensitizing drugs (e.g., Metformin, GLP-1 receptor agonists), androgen blockers (e.g., Spironolactone, oral contraceptives), and topical treatments for specific symptoms.
- Lifestyle Changes: Weight loss, balanced diet, and regular exercise to improve insulin sensitivity and hormone balance.
- Telehealth Services: Platforms like Oana Health offer personalized, at-home care for PCOS management.

This article explores the science behind androgen excess, its impact on health, and the latest treatments, including targeted therapies for different PCOS subtypes.

The Link Between Androgens, Testosterone & PCOS You Need to Know (Balance Your Hormones Naturally)

How Androgen Excess Develops in PCOS

Elevated androgen levels in PCOS stem from a complex interplay of hormonal and metabolic disruptions. Research shows that androgen excess isn't the result of a single issue - it arises from multiple systems working improperly together, including hormonal signaling, metabolic imbalances, and cellular stress. Here's a closer look at the mechanisms driving this condition.

Hormonal Imbalance and the HPO Axis

The hypothalamic-pituitary-ovarian (HPO) axis acts as the body's reproductive command center. Under normal circumstances, GnRH regulates the release of LH and FSH. FSH helps follicles in the ovaries grow, while LH supports estrogen production and triggers ovulation. This balance ensures regular ovulation and proper follicle development.

In PCOS, this system goes awry. Excess androgens increase the frequency of GnRH pulses, which causes an overproduction of LH relative to FSH. This imbalance, commonly seen as an elevated LH/FSH ratio, is a hallmark of PCOS. The excess LH overstimulates theca cells in the ovaries, leading to an overproduction of testosterone and other androgens.

Meanwhile, lower levels of FSH hinder granulosa cells' ability to convert these androgens into estrogens, disrupting normal follicle development. Instead of maturing and ovulating, follicles stop growing prematurely, leading to anovulation. The accumulation of these small, undeveloped follicles gives the ovaries their characteristic "polycystic" appearance on ultrasound.

Adding to this dysfunction, recent studies suggest that androgen receptors in ovarian follicles become prematurely and excessively activated. This may further disrupt GnRH pulsatility and worsen hormonal imbalances. These issues, combined with metabolic factors like insulin resistance, create a cycle of dysfunction.

How Insulin Resistance Affects Androgen Levels

Insulin resistance is a major player in the development of androgen excess in PCOS, affecting up to 75% of women with the condition. When cells resist insulin's signals, the pancreas compensates by producing more insulin, leading to hyperinsulinemia. While this helps regulate blood sugar, the excess insulin fuels androgen production in several ways.

First, high insulin levels directly stimulate theca cells in the ovaries to produce more androgens. Beyond the ovaries, hyperinsulinemia also boosts androgen production in the adrenal glands and fat tissue, making androgen excess a systemic issue.

Second, insulin resistance reduces levels of sex hormone-binding globulin (SHBG), a protein that binds to androgens in the blood to keep them inactive. Lower SHBG means more free androgens, which worsen symptoms like acne, hair loss, and hirsutism.

This creates a vicious cycle: insulin resistance increases androgen levels, and androgens, in turn, contribute to metabolic problems. Studies in animals and humans show that androgen exposure can impair fat tissue function, worsening insulin resistance. In fact, prenatal androgen exposure in certain animal models has been linked to glucose regulation issues in offspring, suggesting that androgens themselves may play a role in metabolic dysfunction.

Insulin resistance also disrupts communication between fat tissue and the endocrine system and alters microRNA expression, further driving androgen excess. Researchers are still uncovering the finer details of these pathways.

New Discoveries in Androgen Production

Recent studies have uncovered additional mechanisms behind androgen excess, revealing that PCOS involves more than just hormonal imbalances - it also includes cellular stress and changes in how cells die.

One key finding is the role of impaired atresia, the natural process where non-maturing follicles are eliminated. In healthy ovaries, most follicles undergo atresia. In PCOS, this process becomes disrupted. Researchers have identified alternative cell death pathways, such as ferroptosis (iron-dependent cell death) and pyroptosis (inflammatory cell death), contributing to ovarian dysfunction.

Excess insulin also disrupts signaling pathways, such as those involving the TGF-β superfamily, further affecting how the ovaries regulate androgen production. Changes in microRNA expression may also play a role in increasing androgen levels, though this remains an area of active research.

Emerging studies have identified distinct PCOS subtypes based on androgen profiles, offering new insights into the condition. A review of over 561,000 women identified four main subtypes:

Hyperandrogenic subtype (HA-PCOS): Found in about 25% of cases, this group has the highest androgen levels and the lowest remission rates. Over half (56%) remain hyperandrogenic over time. This subtype is also linked to complications like second-trimester pregnancy loss and premature membrane rupture due to elevated testosterone levels.
High-SHBG subtype (SHBG-PCOS): Representing 26% of cases, these women have high SHBG levels, low BMI, and lower LH and testosterone levels.
High-LH–AMH subtype (LH-PCOS): Seen in 23% of cases, this group has elevated LH, FSH, and anti-Müllerian hormone levels. It also has one of the lowest remission rates, with only 55.6% achieving hormonal balance over time.
Obesity subtype (OB-PCOS): Accounting for 26% of cases, this group has the best remission rates, with only 31.6% remaining hyperandrogenic. However, they face higher risks of type 2 diabetes (7.9%), dyslipidemia (75.3%), and hypertension (28.7%).

These subtypes highlight the variability in how androgen excess manifests and the importance of tailoring treatment approaches. According to the 2023 International PCOS Guideline, fewer than 20% of women with PCOS do not show hyperandrogenism when screened through clinical or population-based methods. This underscores the central role of androgen excess in the condition and its broad impact on women's health.

Health Effects of Androgen Excess

High androgen levels in PCOS can lead to a range of issues, from challenges with fertility to physical and emotional struggles. These effects highlight the importance of understanding and addressing the hormonal imbalances at the heart of this condition. Recognizing these impacts underscores why early diagnosis and treatment are so critical.

Effects on Fertility and Pregnancy

Excess androgens can make it harder for women to conceive and maintain a healthy pregnancy. Elevated LH, reduced FSH, and overactive theca cells interfere with follicle development, often leading to anovulation. Without regular ovulation, conception becomes a significant challenge, with many women experiencing subfertility or infertility. Additionally, women with hyperandrogenic PCOS may respond less effectively to fertility treatments.

Research indicates that women with the hyperandrogenic (HA-PCOS) subtype face heightened risks during pregnancy compared to those with other PCOS subtypes. These risks include second-trimester pregnancy loss and premature rupture of membranes. Elevated maternal testosterone levels have also been linked to complications such as low birth weight, preterm delivery, and premature rupture of membranes. Scientists suggest that these issues arise from how excess androgens disrupt maternal hormone balance and weaken fetal membrane integrity.

Given these risks, women with severe androgen excess often benefit from thorough preconception planning. This may involve addressing weight management, glucose control, blood pressure, and androgen levels before attempting to conceive. Unfortunately, delayed diagnosis of hyperandrogenism can prolong ovulatory and metabolic challenges, increasing the likelihood of long-term health complications.

These reproductive difficulties often serve as a gateway to broader physical and emotional challenges.

Physical and Emotional Symptoms

Androgen excess doesn’t just affect fertility - it also leaves visible and emotional marks. Many women first seek medical attention due to physical symptoms like hirsutism, acne, and androgenic alopecia. These hallmark signs stem from elevated testosterone and other androgens.

Hirsutism appears as coarse, dark hair in areas such as the face (upper lip, chin, jawline), chest, abdomen, back, and inner thighs. Its severity is often measured using the modified Ferriman-Gallwey scoring system.
Acne tends to persist into adulthood, affecting the face, chest, and back.
Androgenic alopecia, or thinning scalp hair, typically develops at the crown and along the hairline, sometimes progressing to noticeable hair loss.

These physical symptoms can cause embarrassment, diminish self-esteem, and lead to social withdrawal. The emotional toll is significant, with many women experiencing anxiety and depression as a result.

But the psychological effects go beyond appearance. Chronic ovulatory dysfunction and the stress of treatment can compound emotional distress. Sleep disturbances and weight gain - both common in hyperandrogenic PCOS - can further worsen mood disorders. To address these challenges, many healthcare providers now recommend routine mental health screenings for women with PCOS, along with referrals for support when necessary.

The impact of androgen excess extends even further. Women with hyperandrogenic PCOS often face higher metabolic and cardiovascular risks. The link between excess androgens, insulin resistance, obesity, and dyslipidemia increases the likelihood of developing type 2 diabetes and cardiovascular disease over a lifetime. Women with more severe forms of PCOS (characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries) tend to have worse metabolic profiles compared to those with milder cases. Other systemic issues, like sleep apnea and mood swings, can further diminish quality of life.

Recognizing these symptoms early is essential. Women noticing a combination of irregular periods, unwanted facial or body hair, persistent acne, or thinning scalp hair should consult a healthcare provider about possible hyperandrogenism and PCOS. Early evaluation can lead to timely interventions, addressing ovulatory problems, reducing metabolic risks, and alleviating psychological burdens before they escalate into long-term complications.

For those who face obstacles to in-person care, Oana Health offers a telehealth solution. Specializing in PCOS, female hormones, and weight management, Oana Health provides science-based, prescription treatments delivered directly to patients’ homes, ensuring accessible and personalized care.

Testing for Androgen Excess in PCOS

Testing for androgen excess plays a critical role in diagnosing PCOS and differentiating it from other conditions with similar symptoms. These tests help confirm elevated hormone levels and rule out more serious causes, such as androgen-secreting tumors or adrenal disorders. Understanding the available tests and their limitations ensures a more accurate and timely evaluation.

Standard Diagnostic Methods

The 2023 International Evidence-based Guideline for PCOS recommends starting with tests for total and free testosterone to assess androgen levels, one of the three main criteria for diagnosing PCOS in adults.

Total testosterone measures the overall amount of testosterone in the blood. However, standard immunoassays often lack the sensitivity needed to detect the low testosterone levels typical in women. To address this, the guideline suggests using liquid chromatography–tandem mass spectrometry (LC-MS/MS), a more precise method.
Free testosterone measures the active form of testosterone not bound to proteins like sex hormone-binding globulin (SHBG). In cases of low SHBG - common in insulin-resistant or obese women - free testosterone levels may better reflect hyperandrogenism than total testosterone.

If total and free testosterone levels appear normal but clinical signs persist (e.g., facial hair, acne, or hair thinning), second-line tests like androstenedione (A4) and dehydroepiandrosterone sulfate (DHEAS) may be performed. These tests can detect androgen excess in cases where testosterone levels are borderline, though they are less specific to PCOS.

Additional tests often included in the diagnostic process:

LH and FSH: These measure ovulatory function, with an elevated LH/FSH ratio often observed in PCOS, though it is not required for diagnosis.
Anti-Müllerian hormone (AMH): High AMH levels can indicate polycystic ovary morphology, particularly when ultrasound availability is limited.
17-hydroxyprogesterone (17-OHP): Taken during the follicular phase to rule out nonclassic congenital adrenal hyperplasia, a condition that can mimic PCOS.
TSH and prolactin: These help identify thyroid issues or hyperprolactinemia, both of which can cause menstrual irregularities.
Fasting glucose, HbA1c, and lipid profile: These tests assess diabetes risk and cardiovascular health, as PCOS is linked with insulin resistance and metabolic concerns.
Pelvic ultrasound: Used to evaluate ovarian morphology, including the presence of increased antral follicles or larger ovarian volume, which are diagnostic markers for PCOS.

If symptoms like rapid virilization or very high androgen levels are present, imaging (CT/MRI) may be necessary to rule out androgen-secreting tumors or ovarian hyperthecosis.

Clinical evaluation complements lab testing. Tools like the modified Ferriman-Gallwey (mFG) score for hirsutism and visual scales for acne and hair loss help confirm visible signs of androgen excess.

Improving Diagnosis Accuracy

While standard tests lay the groundwork, newer techniques and expanded testing panels are improving diagnostic accuracy. However, challenges remain. Variations in lab reference ranges can complicate interpretation, particularly for women with milder PCOS phenotypes.

Around 20% of women with PCOS may not show clear hyperandrogenism in standard tests despite having clinical symptoms. In these cases, adrenal androgen excess or hormonal fluctuations throughout the menstrual cycle may necessitate repeat or secondary testing.

Ethnic and phenotypic differences also add complexity. Variations in baseline androgen levels, hair distribution, and appropriate mFG thresholds can lead to over- or under-diagnosis. For instance, lean PCOS phenotypes may be overlooked due to the absence of obesity, a common PCOS characteristic. Additionally, research shows that up to 40% of women with regular menstrual cycles but hyperandrogenism have underlying ovulatory dysfunction when formally tested.

Certain groups are at higher risk for misdiagnosis. Adolescents, for example, may experience symptoms like acne, irregular cycles, and multifollicular ovaries due to normal puberty, which can mimic PCOS. The 2023 guideline advises that both menstrual irregularity and clinical or biochemical hyperandrogenism must be present in adolescents to avoid over-diagnosis. Perimenopausal women, on the other hand, require careful evaluation to distinguish PCOS from age-related hormonal changes or androgen-producing tumors.

Advances in testing are addressing these complexities. LC-MS/MS provides more accurate testosterone measurements, reducing false negatives. Broader androgen panels, which include testosterone, androstenedione, DHEAS, and newer markers like 11-oxygenated androgens, help differentiate PCOS from adrenal disorders and reveal distinct androgen patterns.

Research is also refining PCOS classification. A large study from China identified four PCOS subtypes, including a hyperandrogenic group (HA-PCOS) that accounted for 25% of cases. This subtype showed high testosterone and DHEAS levels but fewer metabolic issues. Interestingly, 56% of women in this group remained hyperandrogenic during follow-up. Such findings may eventually lead to more personalized diagnostic thresholds and treatments.

If you’re experiencing symptoms like excessive facial or body hair, cystic acne, thinning scalp hair, difficulty losing weight, or irregular cycles, it’s worth discussing tests for total and free testosterone, SHBG, and possibly DHEAS or androstenedione with your doctor. Proper identification of androgen excess not only confirms PCOS but also helps shape an effective treatment plan.

Treatment Options for Androgen Excess

Managing androgen excess in PCOS involves a combination of strategies targeting both hormonal imbalances and visible symptoms. Since insulin resistance plays a major role in excessive androgen production, many treatments focus on improving insulin sensitivity, while others work to directly block androgens or their effects. Ongoing research is paving the way for more refined therapies, building on the mechanisms of androgen production to restore balance.

Medications That Improve Insulin Sensitivity

Insulin resistance often drives androgen overproduction in PCOS. Elevated insulin levels not only increase androgen production but also suppress SHBG (sex hormone-binding globulin), leaving higher levels of active androgens in the bloodstream.

Medications that improve insulin sensitivity tackle this root cause by reducing insulin levels. This, in turn, helps lower androgen production and allows SHBG levels to rise, reducing free androgen levels.

Metformin is a well-established option for addressing insulin resistance in PCOS. It enhances the body's response to insulin and reduces glucose production in the liver. While it doesn't directly block androgens, lowering insulin levels can indirectly reduce androgen production. Metformin is particularly effective for women with the obesity-related PCOS subtype, which is often linked to higher risks of type 2 diabetes, high cholesterol, and hypertension. However, traditional oral Metformin may cause side effects like nausea or stomach upset. Newer formulations, such as extended-release versions, aim to minimize these issues while maintaining effectiveness.

GLP-1 Receptor Agonists, originally developed for type 2 diabetes, are another promising option. These medications improve insulin sensitivity and promote weight loss, both of which help lower androgen levels. Even a modest weight loss of 5–10% can significantly improve metabolic health.

Medications That Block Androgens

In addition to improving insulin sensitivity, directly targeting androgens is essential for managing both metabolic and visible symptoms. Androgen-blocking treatments can quickly address issues like excess facial and body hair, acne, and hair thinning by either preventing androgens from binding to receptors or reducing their production.

Combined Oral Contraceptives (COCs) are often the first choice for treating hyperandrogenism. They work by suppressing LH (luteinizing hormone) production and raising SHBG levels, which reduces free testosterone and improves symptoms like hirsutism, acne, and irregular periods.

Spironolactone, an androgen receptor blocker, prevents androgens from binding to receptors in hair follicles and sebaceous glands, making it effective for reducing unwanted hair growth and acne. It is often used alongside oral contraceptives when additional symptom management is needed. However, since Spironolactone carries risks during pregnancy, reliable contraception is critical for sexually active women using this medication.

For women with the hyperandrogenic PCOS subtype - characterized by high testosterone and DHEA-S levels - direct androgen-blocking treatments can be particularly helpful. This subtype often requires more aggressive therapy, as persistent hyperandrogenism is common, affecting 56% of patients during follow-ups.

Eflornithine, a topical medication, specifically reduces unwanted facial hair by inhibiting an enzyme necessary for hair growth. It is often combined with other treatments that address hormonal imbalances. Newer formulations that pair Eflornithine with topical Metformin or azelaic acid aim to tackle multiple issues simultaneously, offering targeted symptom relief with minimal systemic side effects.

Monitoring treatment progress regularly ensures effectiveness and helps adjust strategies over time.

Lifestyle Changes and New Treatment Research

Lifestyle changes remain a cornerstone of managing androgen excess, especially for women with insulin resistance. A balanced diet and regular exercise can reduce androgen levels even without medication. Losing just 5–10% of body weight can lead to noticeable improvements in hormone levels, menstrual regularity, and fertility.

Practical dietary tips include focusing on complex carbohydrates instead of refined sugars and maintaining adequate protein intake to support satiety and muscle health.

Regular physical activity is equally important. Aerobic exercises like walking, cycling, or swimming, combined with resistance training, can enhance insulin sensitivity and improve overall fitness. For those on medications like Metformin, exercise also supports bone health and boosts overall well-being.

Research into new treatments is uncovering additional pathways contributing to androgen excess, such as impaired follicular atresia, non-apoptotic cell death mechanisms like ferroptosis and pyroptosis, and disruptions in microRNA expression. Dysregulated signaling between fat tissue and the neuroendocrine system is another area under investigation. Future therapies may target these pathways, including intra-ovarian signaling cascades like TGF-β and PI3K-Akt, to restore normal follicle development and further reduce androgen production.

The shift toward precision medicine in PCOS treatment is gaining momentum. By identifying specific PCOS subtypes - such as hyperandrogenic, obesity-related, high-SHBG, and high-LH-AMH - treatment plans can be tailored to address each subtype's unique risks and challenges. Combining lifestyle changes with emerging therapies offers a more personalized and effective approach.

To complement clinical treatments, telehealth platforms like Oana Health provide personalized, at-home care for women managing PCOS, bridging gaps in traditional healthcare.

Conclusion

Main Points

Androgen excess impacts more than 80% of women with PCOS, contributing to reproductive issues, metabolic problems, and a diminished quality of life. Research shows that fewer than 20% of women with PCOS lack hyperandrogenism, emphasizing the importance of targeted treatments for this condition.

As discussed earlier, insulin resistance plays a key role in driving androgen production while lowering SHBG levels. This connection explains why therapies that improve insulin sensitivity often lead to better management of androgen-related symptoms. Additionally, emerging research into cell death pathways - like ferroptosis and pyroptosis - and disruptions in microRNA are paving the way for more precise therapeutic options in the future.

The move toward research-based PCOS subtypes marks a significant step forward in personalized care. Studies now identify various PCOS subtypes, each responding differently to treatment. This highlights the effectiveness of tailored treatment plans based on individual hormonal and metabolic profiles, rather than relying on generalized approaches.

Managing androgen excess can restore ovulation, improve fertility, reduce pregnancy-related complications, and address visible symptoms like acne and excessive hair growth. It also lowers long-term risks for conditions such as type 2 diabetes and cardiovascular disease. These advancements are shaping a future of more accessible and individualized care.

Accessing PCOS Treatment Through Telehealth

Traditional healthcare often comes with challenges like long wait times, limited access to specialists, and difficulties with follow-up care. Telehealth solutions are stepping in to bridge these gaps, offering personalized treatment options that align with the latest research.

Oana Health is one such platform, providing specialized PCOS care online. After completing a virtual consultation, women are matched with licensed medical professionals who create customized treatment plans based on their symptoms and PCOS subtype. Options include medications like Metformin (starting at $22/month) for insulin resistance, Eflornithine (starting at $69/month) for unwanted hair growth, and Oral Minoxidil (starting at $25/month) for hair loss. All treatments are science-backed and come with free shipping.

For women dealing with insulin resistance, Oana Health offers both oral medications and innovative topical formulations designed to reduce side effects while maintaining effectiveness. Combination treatments are also available, addressing multiple symptoms at once and reflecting the latest research on integrated PCOS management.

Telehealth offers the convenience of avoiding repeated in-person visits while ensuring ongoing support and adjustments to treatment as needed. This is especially beneficial for long-term management of PCOS, which often requires consistent care and monitoring to maintain symptom control and prevent complications.

As research continues to advance our understanding of androgen excess and PCOS subtypes, platforms like Oana Health provide a crucial resource, delivering evidence-based, personalized care that helps women achieve better health and improved quality of life.

FAQs

What role does insulin resistance play in androgen excess in PCOS, and how can it be managed?

Insulin resistance plays a big role in triggering androgen excess in PCOS. When your body stops responding efficiently to insulin, your pancreas ramps up its production, leading to elevated insulin levels. These higher levels can push the ovaries to produce more androgens, like testosterone, which may intensify PCOS symptoms such as acne, excess facial hair, and irregular menstrual cycles.

Addressing insulin resistance often starts with lifestyle adjustments, including eating a balanced diet, staying active with regular exercise, and aiming to maintain a healthy weight. In some situations, doctors may recommend medications to help balance insulin levels and curb androgen production. It's important to work with a healthcare provider to create a treatment plan tailored to your needs.

What are the PCOS subtypes discussed in the article, and how do they impact treatment options?

The article discusses three primary PCOS subtypes: insulin-resistant, inflammatory, and hyperandrogenic. Each type calls for a distinct treatment approach. For instance, insulin-resistant PCOS is commonly addressed with medications that improve insulin sensitivity, while hyperandrogenic PCOS may involve treatments to lower excess androgen levels, such as hormonal therapies or topical solutions. Understanding which subtype you have is crucial for developing a treatment plan that works best for you.

How can Oana Health's telehealth services support women in managing PCOS symptoms?

Oana Health provides personalized telehealth care specifically designed for women managing PCOS. Their approach focuses on addressing common challenges such as unwanted facial hair, hair loss, acne, insulin resistance, weight management, and mental health, all through science-based treatments.

With licensed medical professionals overseeing the process, treatments are prescribed and shipped directly to your doorstep at no extra cost. This ensures a convenient and supportive care experience from start to finish.