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Commentary

Recent Advances in Pharmacologic Management of PCOS: Targeting Androgens, Metabolism and Ovulation

Authors: iyuan Zheng and Renyuan Li, MD*

Publication Date: 23 March

Citation: Zheng S, LI R. Recent Advances in Pharmacologic Management of PCOS: Targeting Androgens, Metabolism and Ovulation. Arch Wom Health 2026; 2(1): 102-104.

Copyright:© 2026 Zheng S., This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Polycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic disorders in women of reproductive age, characterized by hyperandrogenemia, chronic anovulation and insulin resistance. Traditionally, the treatment of PCOS is mainly aimed at symptomatic relief and most of them are over-the-counter medications and there is still no therapeutic drug specifically approved for PCOS1. However, in recent years, important advances have been made in drug treatment strategies targeting the three core features of PCOS. This editorial describes and summarizes established treatments as well as novel therapeutic agents.

 

Keywords: PCOS; Pharmacologic management; Androgens; Metabolism; Ovulation

1. Treatment for Hyperandrogenemia

Combination oral contraceptives (COCs) remain the treatment of choice. COCs are effective in reducing free testosterone by suppressing luteinizing hormone (LH) and increasing sex hormone binding globulin (SHBG) levels1. Low-dose COCs containing anti-androgenic progestins such as drospirenone have been shown to be efficacious in improving hirsutism, acne and menstrual disorders and have a positive effect on metabolic markers2.

 

Spironolactone is widely used as an androgen receptor antagonist in patients with poor symptom control or who cannot tolerate COCs. Studies have shown that spironolactone (100 mg/day for 6-12 months of treatment) reduces hirsutism scores by more than 50% and has no negative effect on body weight, lipids or blood glucose levels3.Other antiandrogenic drugs such as finasteride (5α-reductase inhibitor) and flutamide (androgen receptor blocker) have also been shown to be efficacious2. but the latter is restricted due to higher risk of hepatotoxicity. In recent years a topical androgen receptor inhibitor (clascoterone cream) has been approved for the treatment of acne, giving a new option for topical treatment of androgenic skin symptoms in patients with PCOS.

 

2. Treatments Targeting Metabolic Dysfunction

Insulin resistance is one of the central mechanisms in the pathogenesis of PCOS. Metformin improves insulin sensitivity and reduces hepatic glucose output through activation of the AMPK pathway, which also indirectly reduces ovarian androgen secretion and helps to restore a more regular ovulation cycle2. Recent studies have shown that metformin plays a positive role in modestly improves ovulation rates, menstrual regularity and reduces serum androgen levels in women with PCOS2. Thiazolidinediones (e.g., pioglitazone), on the other hand, improve insulin sensitivity by activating PPAR-γ receptors，increase ovulation rates and improve metabolic markers2.

 

Inositols (e.g., myo-inositol, D-chiral inositol) have received much attention in recent years as natural insulin signaling molecules. Systematic evaluations have noted that inositol improves ovulation rate, insulin sensitivity and menstrual cycle regularity4, but the quality of the evidence is still somewhat controversial and needs to be selected in the context of patient individualization.

 

GLP-1 receptor agonists (e.g., liraglutide, simethicone) have shown superior weight management and metabolic improvement in PCOS by promoting satiety, suppressing appetite and improving insulin sensitivity5. Recent studies have shown that GLP-1 receptor agonists are not only superior to metformin in weight management2,5, but also help to improve the menstrual cycle with lower androgen levels2.

 

Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors, such as dalgogliflozin, improve blood glucose levels and promote weight loss and preliminary studies suggest that it may also improve hormonal profiles and metabolic parameters in PCOS patient1.

 

3. Treatment for Ovulation Disorders

Letrozole, an aromatase inhibitor, has replaced clomiphene as the first-line drug for ovulation induction in PCOS. By inhibiting estrogen synthesis, letrozole relieves negative feedback stimulation of FSH secretion and promotes follicular development. A recent meta-analysis showed that letrozole showed higher ovulation, pregnancy and live birth rate6.

 

Weight loss by GLP-1 receptor agonists or SGLT2 inhibitors followed by ovulation induction has also emerged as an emerging integrative treatment strategy in overweight or obese PCOS patients.

 

In conclusion, important advances have been made in the pharmacologic management of PCOS in recent years. COCs, spironolactone, metformin and letrozole remain the cornerstone of hyperandrogenism management; GLP-1 receptor agonists along with SGLT2 inhibitors offer new options for patients with metabolic disorders. In the future, treatment will be more individualized and precise, integrating to improve the endocrine and metabolic status of PCOS patients to optimize reproductive and long-term health outcomes (Table 1).

 

Table 1: Pharmacologic therapies in PCOS – classes, mechanisms, clinical targets and recent evidence.

Therapy Class

Mechanism of Action

Clinical Targets

Key Recent Findings

Combined Oral Contraceptives

Suppress gonadotropins (↓LH), ↑SHBG (less free T)

Hirsutism, acne; regulate menses

Remain first-line for hyperandrogenism; low-dose combos effectively reduce hirsutism and acne2​pmc.ncbi.nlm.nih.gov​pmc.ncbi.nlm.nih.gov. Anti-androgenic progestins in newer COCs improve metabolic profile.

Anti-androgens (e.g. spironolactone, finasteride)

Block androgen receptor or synthesis (finasteride inhibits 5α-reductase)

Hirsutism, acne (usually adjunct to COC)

Spironolactone 50–200 mg/day significantly reduces hirsutism with minimal side effects3​pmc.ncbi.nlm.nih.gov. Finasteride and flutamide also effective for hirsutism2​pmc.ncbi.nlm.nih.gov, though flutamide use limited by hepatotoxicity.

Metformin (biguanide)

Improves insulin sensitivity; reduces hepatic gluconeogenesis

Insulin resistance; dysglycemia; assists ovulation

Still a staple insulin sensitizer - improves menstrual regularity and ovulation, modest weight loss5​pmc.ncbi.nlm.nih.gov. Often combined with other agents; GI tolerability can limit use.

Inositols (myo-inositol & D-chiro-inositol)

Insulin second messenger; improves insulin signaling and oocyte microenvironment

Insulin resistance; ovulatory dysfunction

Meta-analyses show improved insulin sensitivity and ovulation, comparable to metformin in some studies4​rbej.biomedcentral.com. However, latest evidence reviews deem clinical benefit inconclusive​7pmc.ncbi.nlm.nih.gov.

GLP-1 Receptor Agonists (liraglutide, semaglutide)

Incretin mimetic: ↑insulin (glucose-dependent), ↓glucagon; slows gastric emptying; central appetite suppression

Obesity, metabolic syndrome; secondary benefits on hyperandrogenism and anovulation

Achieve significant weight loss (~5–10%) and ↓insulin resistance in PCOS5​pmc.ncbi.nlm.nih.gov. Superior to metformin for BMI reduction; improves menstrual regularity and lowers androgens in many patients. Gaining acceptance as adjunct therapy in obese PCOS5​pmc.ncbi.nlm.nih.gov.

SGLT2 Inhibitors (dapagliflozin, etc.)

Promote renal glucose excretion (↓blood glucose); osmotic diuresis and mild weight loss

Overweight/obesity; metabolic dysfunction; possibly menstrual regularity

Early trials report ↓body weight, ↓visceral fat and androgen levels and improved cycle frequency1​pmc.ncbi.nlm.nih.gov. Well tolerated; considered promising add-on for PCOS with impaired glucose tolerance.

Aromatase Inhibitors (letrozole)

Inhibit estrogen synthesis, ↑FSH release -> follicular growth

Anovulation (infertility treatment)

Now established 1st-line for ovulation induction in PCOS. Higher ovulation and live birth rates than clomiphene​6mdpi.com. Recent studies confirm letrozole’s efficacy across BMI categories; extended protocols can help letrozole-resistant cases.

 

4. References

  1. Porth R, Oelerich K, Sivanandy MS. The Role of Sodium-Glucose Cotransporter-2 Inhibitors in the Treatment of Polycystic Ovary Syndrome: A Review. J Clin Med, 2024;13: 1056.
  2. Singh S, Pal N, Shubham S, et al. Polycystic Ovary Syndrome: Etiology, Current Management and Future Therapeutics. J Clin Med, 2023;12: 1454.
  3. Rani N, Kumar P, Mishra AK, et al. Efficacy of Spironolactone in Adult Acne in Polycystic Ovary Syndrome Patients an Original Research. J Pharm Bioallied Sci, 2021;13: 1659-1663.
  4. Greff D, Juhász AE, Váncsa S, Váradi A, et al. Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol, 2023;21: 10.
  5. Bader S, Bhatti R, Mussa B, et al. A systematic review of GLP-1 on anthropometrics, metabolic and endocrine parameters in patients with PCOS. Womens Health, 2024;20: 17455057241234530.
  6. Vajna RZ, Géczi AM, Meznerics FA, et al. Strong Early Impact of Letrozole on Ovulation Induction Outperforms Clomiphene Citrate in Polycystic Ovary Syndrome. Pharmaceuticals, 2024;17: 971.
  7. Fitz V, Graca S, Mahalingaiah S, et al. Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines. J Clin Endocrinol Metab, 2024;109: 1630-1655.