How Inflammation Impacts Androgen Production in PCOS

Inflammation plays a key role in Polycystic Ovary Syndrome (PCOS) by driving excess androgen production, which worsens symptoms like irregular periods, acne, hair loss, and weight gain. Chronic low-grade inflammation disrupts ovarian function, increases insulin resistance, and activates genetic pathways that amplify androgen levels. Elevated inflammatory markers like IL-6, TNF-α, and CRP are common in women with PCOS, creating a feedback loop where inflammation and hormone imbalances fuel each other.

Key takeaways:

• Inflammatory molecules (e.g., IL-6, TNF-α) damage ovarian cells, increasing androgens.
• Gene pathways (like NF-κB) are activated by inflammation, further boosting androgen production.
• Immune imbalances (e.g., high Th17/Treg ratio) worsen inflammation and hormone issues.
• Elevated androgens contribute to physical and emotional challenges, including anxiety and depression.

Treatment focuses on reducing inflammation and balancing hormones through:

• Diet and exercise: Anti-inflammatory diets (e.g., Mediterranean) and weight loss improve symptoms.
• Medications: Options like metformin, GLP-1 agonists, and spironolactone address inflammation, insulin resistance, and androgen levels.
• Emerging therapies: Immune-modulating treatments targeting Th17/Treg imbalances are being studied.

Breaking the inflammation-androgen cycle requires a multi-faceted approach that combines lifestyle changes, medications, and personalized care.

Polycystic Ovarian Syndrome (PCOS) - Pathophysiology, Symptoms, Treatment

How Inflammation Triggers Androgen Production

Chronic inflammation doesn't just coexist with PCOS - it actively fuels the production of androgens, creating a complex web of symptoms that are tough to untangle. By digging into the biology, we can see how inflammatory molecules, gene activity, and immune system imbalances work together to drive excess androgen levels.

Inflammatory Molecules and Ovarian Cells

Inflammatory molecules, particularly cytokines like IL-1β, TNF-α, and IL-6, act as direct messengers to ovarian cells, pushing them to ramp up androgen production.

Among these, TNF-α plays a particularly damaging role. It infiltrates ovarian tissue, where it can destroy granulosa cells - the very cells responsible for converting androgens into estrogen. When these cells are damaged, the conversion process halts, leaving higher levels of androgens circulating in the body.

Similarly, IL-6 interferes by inhibiting aromatase, the enzyme that converts androstenedione into estradiol. This disruption leads to a buildup of androgens. Research has shown that elevated IL-6 levels are linked to increased insulin resistance and higher testosterone levels in women with PCOS, regardless of their body weight.

These inflammatory cytokines don’t just disrupt hormone balance - they also activate genetic pathways that further amplify androgen production.

Gene Activation for Androgen Production

Inflammation doesn’t stop at disrupting existing processes - it also flips genetic switches that increase androgen production. For instance, when cytokines like IL-1β and IL-18 bind to ovarian cell receptors, they activate the NF-κB pathway, a key driver of androgen biosynthesis. This pathway upregulates genes such as CYP17A1 and CYP11A1, which are directly involved in the production of androgens.

The CYP17A1 gene is particularly important because it controls the conversion of pregnenolone into androgens, serving as a bottleneck in the production process. When inflammation kicks this gene into overdrive, the ovaries churn out androgens at an accelerated rate.

The NF-κB pathway acts as the central link between inflammation and elevated androgen levels, which is why reducing inflammation often leads to improved hormone balance in women with PCOS.

Immune System Problems and the Cycle

Immune system imbalances add another layer to this cycle of inflammation and androgen excess. Women with PCOS often have an increased number of Th17 cells - pro-inflammatory immune cells - and a reduced number of regulatory T cells (Tregs), which are supposed to keep inflammation in check. This imbalance, reflected in a heightened Th17/Treg ratio, drives ongoing inflammation.

Here’s where it gets even more complicated: Hyperandrogenism, or elevated androgen levels, can stimulate immune cells to release even more inflammatory molecules. This creates a vicious cycle where inflammation triggers androgen production, and those excess androgens, in turn, fuel more inflammation.

Adding to the mix, chronic inflammation in PCOS can activate autoantibodies - proteins that mistakenly attack the body’s own tissues. This autoimmune response further amplifies immune system activity, keeping androgen production high.

This intricate network of inflammation, immune dysfunction, and androgen overproduction highlights why PCOS requires a multi-faceted treatment approach. Addressing just one aspect of the condition won’t break the cycle - it takes a broader strategy to tackle the root causes and interconnected mechanisms.

Important Inflammatory Markers in PCOS

Understanding which inflammatory markers are elevated in PCOS can help both patients and healthcare providers identify the biological factors contributing to androgen excess. These biomarkers shed light on the chronic inflammation that underpins hormonal imbalances, offering a clearer picture of how they differ in women with PCOS compared to those without the condition.

Key Inflammatory Markers and Their Role in PCOS

Several inflammatory biomarkers are consistently elevated in women with PCOS. Each plays a role in fueling androgen excess and disrupting ovarian function.

• C-reactive protein (CRP)
  CRP is a well-known marker of systemic inflammation. Higher CRP levels indicate chronic, low-grade inflammation and are linked to the metabolic risks of PCOS, such as insulin resistance.
• Interleukin-6 (IL-6)
  IL-6 is a pro-inflammatory cytokine that disrupts hormone balance by inhibiting aromatase, the enzyme responsible for converting androgens into estrogens. Studies show that IL-6 levels are elevated in both lean and obese women with PCOS, correlating with insulin resistance and increased testosterone levels.
• Tumor necrosis factor-alpha (TNF-α)
  TNF-α, found in ovarian tissue and follicular fluid, interferes with ovarian function. It can impair granulosa cells, which are essential for converting androgens into estrogens. The presence of TNF-α receptors on egg and granulosa cells underscores its role in reproductive dysfunction.
• Interleukin-1 beta (IL-1β)
  IL-1β, along with interleukin-18 (IL-18), activates inflammatory pathways in ovarian cells. It triggers mechanisms like the NF-κB pathway and the NLRP3 inflammasome, leading to granulosa cell damage and follicular dysfunction, which in turn disrupt androgen balance.
• Th17/Treg Ratio
  An increased Th17/Treg ratio points to immune imbalance and chronic inflammation, emerging as a novel indicator of PCOS.

Comparing Marker Levels: PCOS vs. Healthy Women

When comparing women with PCOS to healthy controls, the differences in inflammatory marker levels highlight the role of inflammation in the condition. These markers are not only elevated in the bloodstream but also in ovarian tissue and follicular fluid, emphasizing that inflammation occurs directly at the site of egg development and hormone production.

Elevated IL-6 and TNF-α levels, in particular, exacerbate insulin resistance and androgen excess, worsening PCOS symptoms. These markers provide valuable insights into the physiological changes driving the condition.

Monitoring these biomarkers can be a powerful tool for identifying patients where inflammation plays a key role in PCOS symptoms. Although these markers are not yet part of standard diagnostic criteria in the U.S., they are increasingly used to evaluate responses to anti-inflammatory treatments and to guide personalized care plans. Current research underscores the importance of addressing both inflammation and androgen excess together, offering a more holistic approach to managing PCOS symptoms and breaking the cycle of inflammation and hormonal imbalance.

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Current and New Treatments for Inflammation and Androgens

Recognizing the role of inflammation in driving androgen excess has shifted treatment strategies for PCOS toward addressing both systemic and localized responses. Tackling inflammation alongside hormonal imbalances is essential to breaking the cycle of PCOS symptoms.

Lifestyle Changes and Anti-Inflammatory Strategies

Dietary changes are a fundamental part of managing PCOS-related inflammation. A Mediterranean-style diet - rich in fruits, vegetables, whole grains, and healthy fats - has been shown to reduce systemic inflammation and lower androgen levels. This works by decreasing inflammatory markers like IL-6 and TNF-α and improving insulin sensitivity, which directly affects ovarian androgen production.

A 5–10% reduction in body weight, achieved through a combination of this diet and at least 150 minutes of moderate exercise each week, can significantly lower inflammatory cytokines and androgen levels. This is because excess body fat contributes to inflammation, so reducing it helps disrupt this harmful cycle.

Metformin, a commonly prescribed medication, improves insulin sensitivity while reducing inflammation and androgen levels by as much as 25%. This dual action makes it particularly effective for women whose PCOS symptoms are linked to both insulin resistance and chronic inflammation.

Stress management is another key component. Practices like mindfulness, yoga, and meditation help reduce cortisol levels, which can exacerbate insulin resistance and inflammation, further complicating hormone balance.

When lifestyle adjustments alone aren't enough, prescription treatments can provide additional support.

Prescription Treatments Through Telehealth

Telehealth services, such as those offered by Oana Health, provide convenient access to prescription treatments tailored for PCOS.

GLP-1 receptor agonists, such as semaglutide, represent a major advancement in PCOS management. These medications promote weight loss, which in turn reduces inflammation and androgen production. Studies show that GLP-1 agonists can lower inflammatory markers like IL-6 and TNF-α while improving metabolic and reproductive outcomes in women with PCOS. Oana Health offers these treatments through their weight loss program, with a combination of oral GLP-1 and metformin available for $199 per month.

Spironolactone, an anti-androgen medication, blocks androgen receptors, helping to alleviate symptoms such as acne and unwanted facial hair. While primarily hormonal in its action, it may also reduce inflammation in skin and other tissues. Oana Health provides spironolactone starting at $14 per month, with combination packs including metformin available for $32 per month.

Topical treatments offer a targeted solution for managing PCOS symptoms with fewer systemic side effects. For example, topical metformin can address local inflammation and androgen production in the skin, helping with acne and hirsutism. Oana Health offers metformin HCL lotion 20% for $43 monthly, as well as specialized formulations like Hairless Hype for $69 monthly, which combines eflornithine, metformin lotion, and azelaic acid to tackle unwanted hair growth.

Telehealth platforms make these treatments accessible, especially for women who may not have easy access to specialized PCOS care. This approach allows for personalized treatment plans, regular monitoring, and medication adjustments without the challenges of traditional healthcare visits.

Immune System-Based Treatments

Emerging therapies are focusing on immune system modulation to address PCOS-related inflammation. Research highlights the Th17/Treg cell imbalance as a significant contributor to chronic inflammation in PCOS. Women with PCOS often have elevated pro-inflammatory Th17 cells and reduced anti-inflammatory regulatory T cells (Tregs), perpetuating inflammation and androgen excess.

Experimental therapies are exploring ways to restore this immune balance. These include biologics or small molecules designed to target specific immune pathways, aiming to address the root causes of inflammation rather than just its symptoms. While these treatments are still in the research phase, they hold promise for future clinical use.

Current studies are investigating compounds that can suppress Th17 activity and enhance Treg function. These cutting-edge approaches could complement existing therapies, offering new ways to reduce inflammation and androgen levels.

Combining immune modulation with established treatments represents the next frontier in PCOS care. As our understanding of the link between inflammation and androgens deepens, these therapies could provide new hope for women who don't respond well to current options.

Comparative research consistently demonstrates that combining lifestyle changes with prescription medications yields the best results. This integrated approach leads to greater reductions in IL-6, TNF-α, and testosterone levels compared to either strategy alone. By addressing multiple aspects of the inflammation-androgen cycle, comprehensive treatment plans offer the most effective path forward.

Conclusion: Treating the Inflammation-Androgen Connection in PCOS

Chronic inflammation plays a key role in triggering ovarian androgen production, creating a cycle of hormonal imbalance that feeds into itself. Elevated androgen levels, in turn, intensify inflammatory responses, locking women with PCOS into this persistent loop.

Understanding this connection has shifted the focus of PCOS management. Instead of addressing symptoms in isolation, targeting inflammation offers a pathway to achieving lasting hormonal balance. Research consistently shows that women with PCOS have higher levels of inflammatory markers like TNF-α and IL-6 compared to those without the condition. These markers are closely linked to increased androgen production. This knowledge forms the basis for more integrated treatment strategies.

The most effective approaches tackle both inflammation and androgen excess simultaneously. By combining anti-inflammatory lifestyle changes with targeted prescription treatments, women can break free from this cycle. Telehealth services make this even more accessible, offering convenient, comprehensive care options.

Personalized care is the cornerstone of effective PCOS treatment. Every woman’s hormonal and inflammatory profile is different, so generic solutions often miss the mark. Telehealth platforms like Oana Health are reshaping PCOS care by delivering tailored, science-backed treatments directly to patients’ homes, ensuring care is both accessible and individualized.

Looking ahead, the future of PCOS treatment lies in even more precise interventions. As research continues to explore the immune–endocrine connection, therapies targeting specific immune pathways, such as the Th17/Treg imbalance, show promise. Patients are already benefiting from practical innovations like topical treatments:

"I'm so glad I discovered Oana's metformin lotion! I used to struggle a lot with the side effects for oral metformin and this is a great alternative for me. I get the same benefits but no more upset stomach and nausea, and this helps me stick with it a lot more consistently." - Carrie S., Topical Metformin User

FAQs

How does chronic inflammation lead to increased androgen production in women with PCOS?

Chronic inflammation is a key factor in driving increased androgen production in women with PCOS. It can prompt the ovaries and adrenal glands to produce more androgens, like testosterone. This happens because inflammation interferes with normal hormonal signaling, leading to an overproduction of these hormones.

On top of that, inflammation often worsens insulin resistance - a common challenge for those with PCOS. Higher insulin levels can push the ovaries to produce even more androgens, creating a cycle that intensifies symptoms such as irregular menstrual cycles, acne, and excessive hair growth. Tackling inflammation through tailored lifestyle adjustments, medical interventions, and focused care can play a vital role in managing these symptoms.

What lifestyle changes can help reduce inflammation and androgen levels in PCOS?

Lifestyle adjustments can make a big difference in managing inflammation and lowering androgen levels for those dealing with PCOS. Eating a nutrient-rich diet filled with whole foods like vegetables, fruits, lean proteins, and healthy fats can help keep inflammation in check. Cutting back on processed foods, added sugars, and refined carbs can also be a smart move.

Staying active is just as important. Moderate exercises like walking, swimming, or strength training can boost insulin sensitivity and help reduce inflammation. On top of that, finding ways to manage stress - whether through mindfulness, yoga, or meditation - can support hormone regulation and improve overall health.

For those looking for tailored support, Oana Health provides science-based treatments designed to help with weight management and hormonal balance for individuals with PCOS.

How does inflammation affect androgen levels in women with PCOS?

Inflammation plays a key role in driving up androgen levels in women with PCOS. When the immune system is out of balance, it can trigger chronic, low-grade inflammation. This ongoing inflammation prompts the ovaries and adrenal glands to produce more androgens, like testosterone, which can intensify PCOS symptoms such as irregular menstrual cycles, acne, and excessive hair growth.

Studies also point to an imbalance in immune cells - specifically the Th17/Treg ratio - as a possible factor in fueling this cycle of inflammation and elevated androgens. Tackling inflammation through specific treatments and lifestyle adjustments can help regulate androgen levels and ease PCOS symptoms overall.

Related Blog Posts

• Inflammation and Insulin Resistance in PCOS
• Inflammation and PCOS: Key Connections
• Research: Anti-Inflammatory Diet and Androgen Levels
• Immune Modulators in PCOS: How They Work