Top 5 Anti-Androgen Medications for PCOS

Polycystic Ovary Syndrome (PCOS) affects millions of women and often causes high androgen levels, leading to symptoms like acne, excess hair growth, hair thinning, and irregular periods. Anti-androgen medications help manage these symptoms by reducing or blocking androgen activity. Here’s a quick look at the top options:

• Spironolactone: Reduces androgen effects, treats acne, hirsutism, and hair loss. Requires regular monitoring for potassium levels.
• Finasteride: Blocks DHT production, primarily used for hirsutism. Not safe during pregnancy.
• Flutamide: Blocks androgen receptors, effective for acne and hair-related symptoms but carries a risk of liver toxicity.
• Cyproterone Acetate: Common outside the U.S., reduces androgens and regulates periods but has higher clotting risks.
• Drospirenone-containing COCs: Combines a progestin with estrogen to manage PCOS symptoms and regulate cycles but increases clot risks.

Each medication has unique benefits, side effects, and monitoring needs. Choosing the right one depends on your symptoms, medical history, and goals. Regular follow-ups with a healthcare provider are essential for safe and effective treatment.

Symptomatic management of PCOS With Dr.Anita Dileep | MedSynapse

1. Spironolactone

Spironolactone plays a key role in managing PCOS symptoms by targeting multiple pathways related to androgen activity. Interestingly, this medication was originally developed to treat high blood pressure, but its ability to address hormonal imbalances has made it a valuable option for tackling androgen-related issues in PCOS.

How It Works

Spironolactone reduces the effects of androgens in several ways. It blocks androgen receptors, stopping testosterone and dihydrotestosterone (DHT) from binding to cells, which helps normalize hair and skin function. Additionally, it partially inhibits the production of steroids in the ovaries and adrenal glands and interferes with enzymes like 5α-reductase and 17-hydroxysteroid dehydrogenase, which convert testosterone into its more potent form, DHT. On top of that, it boosts aromatase activity to convert androgens into estrogens and raises levels of sex hormone binding globulin (SHBG), which reduces the amount of free, active androgens in the body. Together, these mechanisms make spironolactone a powerful tool for managing PCOS symptoms.

Symptoms It Addresses

Spironolactone is particularly effective in treating hirsutism, acne, and androgenic alopecia. Improvements in these symptoms often start to appear within 3–6 months, with the best results typically seen around 12 months. It’s especially helpful for hormonal acne, such as breakouts along the jawline and chin that tend to worsen during menstrual cycles. For hair thinning, it may slow the process and, in some cases, even lead to modest regrowth.

Possible Side Effects

Like any medication, spironolactone comes with potential side effects. The most serious concern is hyperkalemia, or elevated potassium levels, which is especially risky for people with kidney problems or those taking potassium-sparing drugs. Other common issues include menstrual irregularities, with approximately 30% of users experiencing intermenstrual bleeding. Some people may also notice increased urination, dizziness, fatigue, muscle cramps, headaches, or mild gastrointestinal discomfort. A long-term study revealed that while 60% of patients reported side effects, only 15% stopped taking the medication. The most frequently reported issues were diuretic effects (29%), menstrual irregularities (22%), and breast tenderness (17%).

Monitoring and Safety

To ensure safe use, regular blood tests are essential to monitor potassium levels, kidney function, and sodium levels. Initial baseline tests followed by periodic check-ups help identify any issues early. Spironolactone is not suitable for individuals with hyperkalemia, significant kidney impairment (serum creatinine >2.0 mg/dL or eGFR <30 mL/min), or Addison’s disease. Those at higher risk - such as individuals over 45 or those with diabetes, heart conditions, or kidney disease - may need more frequent monitoring.

Pregnancy prevention is also critical while using spironolactone, as it can affect fetal development, potentially causing feminization of male fetuses. Women of childbearing age should use effective contraception and stop the medication if planning to conceive. It’s generally safe to try for pregnancy about a month after discontinuing spironolactone.

For personalized PCOS care, check out Oana Health, where you can get spironolactone prescriptions starting at $14 per month, delivered right to your door.

2. Finasteride

Finasteride is a medication that has found a role in addressing hirsutism in women with PCOS. While originally used for conditions like hair loss and prostate issues, it is now prescribed off-label to help reduce unwanted hair growth associated with PCOS.

Mechanism of Action

Finasteride works by blocking the enzyme 5-alpha reductase, which is responsible for converting testosterone into dihydrotestosterone (DHT), a more potent androgen. By reducing DHT levels, finasteride helps improve hair growth patterns and directly targets the excessive hair growth often seen in PCOS patients.

Key PCOS Symptoms Targeted

The primary benefit of finasteride in PCOS is its ability to reduce hirsutism. Clinical studies show that finasteride can lower hirsutism scores by 26–60% after 6–12 months of treatment. Some women report noticeable improvements within 3 months, with the most significant changes typically occurring around the 6-month mark.

"Finasteride can be recommended for PCOS patients with hirsutism, particularly those with refractory symptoms or endocrine co-morbidities, as it effectively reduces hirsutism scores by inhibiting 5α-reductase activity." – Dr.Oracle Medical Advisory Board & Editors

Research also suggests that combining finasteride with other medications, such as spironolactone or cyproterone acetate paired with ethynyl estradiol, can result in even greater reductions in hirsutism scores compared to using spironolactone alone. This makes finasteride a valuable option, especially for patients who do not respond adequately to other treatments.

Common Side Effects

Like any medication, finasteride comes with potential side effects. Commonly reported issues include:

• Headaches
• Nausea
• Weight gain
• Breast tenderness
• Decreased libido
• Dizziness
• Menstrual irregularities
• Dry skin

A decrease in libido has been observed in approximately 5.2% to 10.5% of patients. Importantly, women must avoid pregnancy while taking finasteride, as it can cause severe birth defects, particularly affecting the external genitalia of male fetuses. For this reason, finasteride is not suitable for women who are pregnant, trying to conceive, or breastfeeding. Women of reproductive age must use effective contraception while on this medication.

Some studies suggest that women who are premenopausal may experience side effects more frequently. To minimize these effects, intermittent dosing (e.g., 2.5 mg every 3 days) has been explored and may reduce issues like decreased libido compared to daily dosing. Rare but serious side effects, such as persistent sexual dysfunction, Post-Finasteride Syndrome (PFS), or severe allergic reactions, have also been reported [15, 21].

Monitoring Requirements

As with other anti-androgen treatments, regular monitoring is essential to ensure both safety and effectiveness. Follow-up appointments with a healthcare provider are necessary to evaluate the response to treatment, particularly improvements in hirsutism, and to address any side effects. Women of childbearing age must adhere strictly to contraception guidelines while taking finasteride to avoid potential risks.

3. Flutamide

Flutamide, initially developed to treat prostate cancer, has found a role in managing PCOS-related hyperandrogenism, addressing symptoms like acne, hirsutism, hair loss, and ovulatory dysfunction. However, its use requires careful attention due to the risk of liver toxicity, making personalized dosing and regular monitoring essential.

Mechanism of Action

Flutamide works by converting into hydroxyflutamide, a metabolite with a much stronger affinity (10–25 times greater) for androgen receptors. This blocks the effects of testosterone and DHT, two key androgens implicated in PCOS symptoms. It also slightly inhibits androgen production by targeting CYP17A1. Unlike some other treatments, flutamide does not exhibit progestogenic, estrogenic, glucocorticoid, or antigonadotropic activity, ensuring its effects are primarily focused on reducing androgen activity.

Key PCOS Symptoms Targeted

Flutamide has shown significant results in improving acne, hirsutism, and hair loss:

• Acne: Studies highlight up to 90% resolution of acne compared to 40% with spironolactone. Within three months, 80% reductions in acne and seborrhea scores were reported, with 97% of women expressing satisfaction with acne control.
• Hirsutism: Ferriman–Gallwey scores, which measure excess hair growth, dropped significantly from 16.4 ± 3.2 to 6.0 ± 1.5 after six months of treatment.
• Hair Loss: A 21% improvement in Ludwig scores for female pattern hair loss was observed after one year of use.

Additional benefits include restored ovulatory cycles and improved uterine blood flow, supporting its broader role in PCOS management.

"The most important result of the present study was that flutamide restored ovulation in anovulatory PCOS patients." – Vincenzo De Leo, et al.

Common Side Effects

Flutamide carries a black box warning for severe liver toxicity. While rare, liver failure occurs in about 0.03% of patients (3 in 10,000). Elevated liver enzymes are more common, affecting 42–62% of users, with severe cases occurring in 3–5%, particularly within the first three months of treatment.

Other side effects include:

• Dry Skin: Reported in about 75% of patients due to decreased sebum production.
• Gastrointestinal Issues: Diarrhea affects 12–26%, with approximately 6% discontinuing treatment as a result. Nausea, vomiting, and appetite loss are seen in about 10% of users.
• Less Common Effects: These include swelling, low white blood cell counts, rash, dizziness, and harmless greenish-blue urine discoloration. Rare but serious reactions include interstitial pneumonitis (0.04% incidence), photosensitivity, and blood disorders.

Flutamide is contraindicated in women trying to conceive due to the risk of severe birth defects in male fetuses.

Monitoring Requirements

Given the potential for liver toxicity, strict monitoring is non-negotiable. Liver function tests are required at baseline and then monthly for the first four months. Therapy should be discontinued if jaundice develops or if ALT levels double the normal range. Patients must be vigilant for symptoms of liver dysfunction, such as abdominal pain, nausea, vomiting, jaundice, or changes in urine color. Additionally, women of reproductive age must undergo pregnancy testing, as flutamide is classified as Category D for pregnancy.

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4. Cyproterone Acetate

Cyproterone acetate (CPA) isn’t approved for use in the United States, but it’s a common treatment option in other parts of the world, including Europe and Canada. In these regions, CPA is often prescribed alongside ethinylestradiol in medications like Diane-35. While the U.S. relies on different therapies, CPA remains a prominent choice abroad for addressing hyperandrogenism and symptoms of polycystic ovary syndrome (PCOS).

Mechanism of Action

CPA works as an anti-androgen, but its approach is distinct. This 21-carbon steroid has progestogenic and mild glucocorticoid properties, helping reduce androgen activity by blocking androgen receptors and suppressing luteinizing hormone (LH) secretion.

"Cyproterone acetate acts as an antiandrogen by competing with DHT and testosterone for binding to the androgen receptor. There is also some evidence that cyproterone acetate and ethinyl estradiol in combination can inhibit 5α-reductase activity in skin." (Williams Textbook of Endocrinology, Twelfth Edition, 2011)

Its progestational effects create a feedback mechanism that lowers ovarian androgen production by reducing LH levels. When paired with ethinylestradiol, the estrogen boosts the liver’s production of sex hormone-binding globulin (SHBG), which decreases the amount of free, active testosterone circulating in the body.

Key PCOS Symptoms Targeted

CPA is effective in managing various hyperandrogenic symptoms tied to PCOS. For instance, low-dose CPA/ethinylestradiol combinations improve acne in 75–90% of women. When it comes to hirsutism, a 2 mg dose of CPA delivers results comparable to 50 mg of spironolactone. It also helps with androgenic alopecia and seborrhea by addressing the underlying androgen imbalance. Additionally, CPA’s progestogenic properties assist in regulating menstrual cycles, making them more predictable.

Common Side Effects

While CPA is effective, it comes with a range of potential side effects, including:

• Sexual dysfunction: Reduced libido and vaginal dryness
• Weight gain: Often linked to fluid retention and increased fat storage
• Breast tenderness and swelling: A common complaint among users
• Mood changes: Fatigue, depression, anxiety, and mood swings
• Gastrointestinal and vasomotor symptoms: Nausea, vomiting, hot flashes, and sweating

More serious risks include a higher likelihood of developing meningiomas, a rare but benign brain tumor. This risk is particularly notable with prolonged use of doses at 25 mg per day or higher, affecting roughly 1 to 10 in 10,000 patients. CPA also increases the risk of venous thromboembolism (VTE), with studies estimating a 50% to 100% higher risk compared to contraceptives containing levonorgestrel. The pooled relative risk is around 1.6–1.8.

Monitoring Requirements

Given its side effect profile, CPA requires close medical supervision. Key monitoring measures include:

• Liver function tests: Regular checks are crucial, as CPA can lead to liver toxicity, especially at doses of 100 mg or more. Symptoms like jaundice, dark urine, or severe abdominal pain should not be ignored.
• Neurological monitoring: Watch for symptoms such as persistent headaches, vision changes, hearing loss, or memory issues, which could signal meningiomas. CPA should be discontinued if these occur.
• Blood tests: Routine blood counts and hormone level monitoring (especially testosterone) help track treatment progress.
• Blood sugar monitoring: Particularly important for diabetic patients, as CPA may affect glucose control.
• Cardiovascular checks: Blood pressure monitoring and screening for signs of blood clots are essential due to the increased VTE risk.
• Bone density scans: Long-term users may need periodic bone density evaluations to check for potential osteoporosis.

Close medical oversight ensures that CPA’s benefits outweigh its risks, offering effective symptom relief while minimizing adverse effects.

5. Drospirenone-Containing Combined Oral Contraceptives

Drospirenone-containing combined oral contraceptives (COCs) are often the go-to treatment for women with PCOS who aren't planning to conceive. These medications pair ethinyl estradiol with drospirenone, a synthetic progestin chemically related to spironolactone. Popular brands include Yasmin and Yaz.

Like other anti-androgen therapies, these COCs not only manage specific symptoms but also address the hormonal imbalances that drive PCOS.

How They Work

Drospirenone-containing COCs take a multi-pronged approach to managing PCOS. First, they suppress the release of gonadotropins - luteinizing hormone (LH) and follicle-stimulating hormone (FSH) - to prevent ovulation and reduce ovarian androgen production.

Drospirenone itself blocks androgen receptors and reduces the binding of dihydrotestosterone (DHT), leading to lower androgen levels from both the ovaries and adrenal glands. This includes reductions in testosterone, androstenedione, and dehydroepiandrosterone sulfate (DHEAS). It also inhibits enzymes involved in androgen production.

The ethinyl estradiol component complements these effects by boosting the liver's production of sex hormone-binding globulin (SHBG). Higher SHBG levels mean more testosterone is bound and inactive, leaving less free testosterone in circulation.

Additionally, drospirenone has antimineralocorticoid properties, blocking aldosterone receptors. This helps the body excrete excess sodium and water.

Symptoms Addressed in PCOS

These COCs are particularly effective in tackling hyperandrogenism. Studies show they reduce acne severity and improve hirsutism scores. They also lower biochemical markers like testosterone levels and the Free Androgen Index.

Menstrual irregularities are another area where these medications shine. In a study of 140 women with PCOS, 98.57% experienced withdrawal bleeding, and 80.71% reported normalized menstrual cycles after three months of treatment with 3 mg drospirenone and 20 μg ethinyl estradiol. These medications help regulate erratic periods and restore a more predictable cycle. Research even suggests they can reduce ovarian volume, which may improve the polycystic appearance often seen on ultrasound. For some women, these COCs also help ease symptoms of premenstrual dysphoric disorder (PMDD).

"COCs, in addition to lifestyle modifications, represent the first-line treatment in most women with PCOS if fertility is not desired, in order to regulate the menstrual cycle and improve clinical signs of hyperandrogenism." - Seda Hanife Oguz & Bulent Okan Yildiz, Endocrinology and Metabolism (2021)

Possible Side Effects

While effective, drospirenone-containing COCs do come with potential side effects. A key concern is the increased risk of venous thromboembolism (VTE), with 8–10 events per 10,000 woman-years reported - higher than with levonorgestrel-containing alternatives. There's also a 1.6-fold increased risk of arterial thrombosis in premenopausal women using these COCs.

The estrogen component can raise blood pressure by increasing angiotensinogen production. Other metabolic changes include higher triglycerides, LDL cholesterol, and HDL cholesterol levels. Some studies note increases in total and truncal fat percentage after six months of use, despite no changes in BMI.

In the same study of 140 women with PCOS, 57.86% reported no side effects, but 42.14% experienced issues like breast swelling and pain (14.29%), irregular bleeding (35.71%), dizziness and headaches (2.86%), and gastrointestinal discomfort (0.72%). Other common but manageable side effects include nausea (especially early on), mood swings, fatigue, and skin discoloration. Drospirenone's antimineralocorticoid action can also lead to hyperkalemia, particularly in those with kidney, liver, or adrenal conditions.

Monitoring During Treatment

Starting drospirenone-containing COCs requires a thorough evaluation and regular follow-ups. The initial assessment should cover cardiovascular risk factors, migraine history, depression, and any family history of blood clots.

Because drospirenone can affect potassium levels, monitoring is advised for high-risk individuals or those taking medications like ACE inhibitors, NSAIDs, or potassium-sparing diuretics. Follow-up visits are typically scheduled after three months to check BMI, waist circumference, and blood pressure. Hirsutism improvements are usually assessed after six months, as noticeable changes can take time.

"It is also emphasized that a minimum duration of 6 months is required to assess treatment response regarding hirsutism." - Seda Hanife Oguz & Bulent Okan Yildiz, Endocrinology and Metabolism (2021)

Patients should be educated about side effects and serious complications like blood clots. Warning signs include leg swelling, severe headaches, vision changes, chest pain, and muscle weakness. Additionally, avoiding grapefruit products and using sunscreen can help prevent skin discoloration.

For personalized advice and monitoring, healthcare providers at Oana Health can guide you in determining whether drospirenone-containing COCs are the right option for managing your PCOS symptoms. They’ll also provide ongoing support throughout your treatment journey.

Medication Comparison Table

Here’s a concise comparison of five anti-androgen medications for PCOS, focusing on their mechanisms, targeted symptoms, effectiveness, side effects, monitoring needs, and cost. This table summarizes key details to help guide treatment decisions.

Research shows that anti-androgens combined with lifestyle changes outperform metformin paired with lifestyle interventions for reducing hirsutism (weighted mean difference: −1.59, p = 0.03).

Safety and Monitoring

Safety profiles vary significantly. Spironolactone and drospirenone-containing COCs are considered safer options with manageable side effects, while flutamide carries a higher risk of liver toxicity, requiring close monitoring. Cyproterone acetate, though effective, is less favored due to its safety concerns and is unavailable in the United States.

Cost and Accessibility

Cost is an essential factor. For instance, Oana Health offers oral spironolactone at $14 per month, making it one of the more affordable options. Topical spironolactone, priced at $43 monthly, may provide effective results for hair-related symptoms with fewer systemic side effects.

Choosing the Right Treatment

Monitoring needs also differ. Medications like flutamide and drospirenone-containing COCs require additional checks for liver function or cardiovascular risks. Ultimately, the best medication depends on your symptoms, medical history, and treatment goals. Providers like Oana Health can help you find the right fit, offering personalized treatment plans delivered directly to your door.

Conclusion

Managing PCOS effectively requires a tailored approach to anti-androgen therapy, one that takes into account your specific symptoms, medical history, and personal treatment goals. As researchers have noted, "treatments of PCOS must be tailored to the specific needs of each patient; goals of therapy may include ameliorating hyperandrogenic symptoms, inducing ovulation, regulating menstruation, and preventing cardiometabolic complications".

There isn’t a one-size-fits-all solution when it comes to PCOS. Finding the right treatment often involves ongoing evaluation and adjustments. This highlights the importance of individualized care and consistent monitoring throughout your treatment journey.

Medical supervision plays a crucial role, especially when anti-androgens are considered after first-line treatments, like combined oral contraceptives, fail to deliver the desired results after at least six months. During this process, healthcare providers assess individual risk factors, monitor for potential side effects, and make necessary adjustments to ensure the treatment is both safe and effective.

For added convenience, telehealth services like Oana Health offer access to licensed professionals who specialize in hormonal health and PCOS care. They provide options such as spironolactone, starting at $14 per month, delivered straight to your door.

Effective PCOS care combines systemic and symptom-specific strategies. As Aya A. Muhammed Saeed and colleagues explained, "This personalized treatment approach focuses on both systemic and symptom-specific aspects of PCOS to enable better reproductive and metabolic health". Whether you're addressing acne, unwanted hair growth, hair loss, or irregular cycles, working with knowledgeable healthcare providers ensures you receive the most suitable anti-androgen therapy for your unique needs.

If you're ready to take the next step in managing PCOS, reach out to Oana Health and connect with specialists who can guide you toward the right treatment plan.

FAQs

What should I consider when selecting an anti-androgen medication for PCOS?

When choosing an anti-androgen medication for PCOS, it's crucial to assess the severity of your symptoms, such as excessive facial hair, acne, or hair thinning. Equally important is evaluating how well the medication works to lower androgen levels and considering any potential side effects.

You should also factor in your overall health, any ongoing treatments, and whether the medication will be combined with hormonal therapies like birth control pills. Be sure to consult with a licensed healthcare professional to develop a treatment plan that suits your specific needs.

What lifestyle changes can help anti-androgen medications work better for PCOS?

Making adjustments to your daily habits can play a big role in boosting the effectiveness of anti-androgen medications for managing PCOS. Incorporating regular exercise - like a combination of aerobic workouts and strength training - can improve insulin sensitivity, aid in weight control, and help reduce symptoms such as acne and excess hair growth.

Eating a well-balanced diet and shedding extra pounds, if necessary, can also help regulate hormones and enhance your treatment outcomes. Even small steps, like prioritizing whole, nutrient-rich foods, managing stress levels, and ensuring quality sleep, can have a positive impact on your overall health and the management of PCOS symptoms.

What’s the best way to manage side effects of anti-androgen medications for PCOS?

To safely handle potential side effects of anti-androgen medications, staying in close contact with your healthcare provider is key. They can keep an eye on serious concerns like liver issues, electrolyte imbalances, or shifts in blood cell counts. If you notice anything unusual or experience unexpected side effects, let them know immediately.

You can also play an active role in supporting your treatment by embracing a healthy lifestyle. Focus on eating a well-rounded diet, staying active, and managing your weight. These steps not only help minimize side effects but can also enhance the overall effectiveness of your treatment. Regular follow-ups with your provider will ensure your treatment plan remains safe and tailored to your needs.

Related Blog Posts

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• Anti-Androgens for PCOS: Are They Safe Long-Term?
• Top 5 Anti-Androgen Medications for Hirsutism
• Anti-Androgens in PCOS: Mechanisms Explained