Spironolactone and metformin combination therapy as a potential non-hormonal treatment for management of hyperandrogenic symptoms of polycystic ovarian syndrome
Introduction: Polycystic ovarian syndrome (PCOS) is one of the most common endocrinological conditions in women of child-bearing age.1 It is characterised by symptoms of oligo- or anovulation, hyperandrogenism and polycystic ovarian morphology.2 Current mainstay treatment for PCOS involves off-label...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
|
| Series: | Clinical Medicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1470211825001794 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849254262237822976 |
|---|---|
| author | Irene Karderinis Yangxinrui Ma Telma Viveiros Neha Deshpande Bassel Watter Vikram Talaulikar |
| author_facet | Irene Karderinis Yangxinrui Ma Telma Viveiros Neha Deshpande Bassel Watter Vikram Talaulikar |
| author_sort | Irene Karderinis |
| collection | DOAJ |
| description | Introduction: Polycystic ovarian syndrome (PCOS) is one of the most common endocrinological conditions in women of child-bearing age.1 It is characterised by symptoms of oligo- or anovulation, hyperandrogenism and polycystic ovarian morphology.2 Current mainstay treatment for PCOS involves off-label use of combined oral hormonal contraception (COC).3 However, use of COC carries several contraindications and cautions. There is growing evidence that anti-androgen agents could be a potential effective non-hormonal treatment for hyperandrogenic symptoms of PCOS.4–6 This review focused on available randomised control trials (RCT) evaluating use of spironolactone, alone or in combination with other non-hormonal treatments for: (1) the management of hyperandrogenic symptoms of PCOS; (2) its side-effect profile; and (3) burden on patients. Materials and Methods: Following PROSPERO registration (CRD42023404914), an electronic search was performed on MEDLINE, EMBASE, PUBMED, CENTRAL and SCOPUS. Abstracts were screened against inclusion and exclusion criteria. Studies were assessed for risk of bias using standard tools, and three studies with intermediate bias risk were included in this meta-analysis. Data were analysed using STATA V13 and Open Meta-analyst software. Results and Discussion: This meta-analysis included four clinical trials.7–10 The length of these trials ranged from 6 to 24 months. They] focused on the comparison of spironolactone and metformin monotherapy, as well as the effects of combination effect on hirsutism, body mass index (BMI) and testosterone levels.Spironolactone monotherapy and metformin monotherapy did not affect testosterone levels (n=3, weighted mean (WMD) -0.06, 95% confidence interval (Cl) -0.33 to 0.20, I2 46.62%). The clinical trials showed minimal evidence to support that spironolactone improved BMI (n=3, WMD -0.22, 95% Cl -1.07 to 0.62, I2 0%) and hirsutism compared with metformin (n=3, WMD -0.27, 95% Cl -1.07 to 0.53, I2 64.44%). Additionally, spironolactone in combination with metformin did not appear to have an advantage over use of metformin in relation to BMI (n=3, WMD 0.35, 95% Cl -1.25 to 1.94, I2 84.4%), hirsutism (n=3, WMD -0.10, 95% Cl -0.66 to 0.46, I2 22.8%) and blood testosterone levels (n=3, WMD -0.35, 95% Cl -0.57 to -0.12, I2 48.4%).None of the studies reported any major adverse events with use of spironolactone.Significant heterogeneity was observed across the studies, and the overall quality of evidence in this systematic review was moderate. Our findings emphasise the lack of high-quality data on non-hormonal treatments for hyperandrogenic symptoms of PCOS. Further research is needed to explore alternative treatment options, particularly for individuals who cannot use hormonal contraceptives because of side effects or medical contraindications. Conclusion: Currently, there is a lack of randomised evidence available that supports the use of spironolactone, either alone or in combination with metformin, for women with PCOS. Additional trials are necessary to determine its benefits before routinely recommending it as a treatment. |
| format | Article |
| id | doaj-art-d4e4c85c26ff41dab3aedd3815fce18d |
| institution | Kabale University |
| issn | 1470-2118 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Clinical Medicine |
| spelling | doaj-art-d4e4c85c26ff41dab3aedd3815fce18d2025-08-20T03:56:04ZengElsevierClinical Medicine1470-21182025-07-0125410046110.1016/j.clinme.2025.100461Spironolactone and metformin combination therapy as a potential non-hormonal treatment for management of hyperandrogenic symptoms of polycystic ovarian syndromeIrene Karderinis0Yangxinrui Ma1Telma Viveiros2Neha Deshpande3Bassel Watter4Vikram Talaulikar5University College LondonUniversity College LondonUniversity College LondonUniversity College LondonUniversity College LondonUniversity College LondonIntroduction: Polycystic ovarian syndrome (PCOS) is one of the most common endocrinological conditions in women of child-bearing age.1 It is characterised by symptoms of oligo- or anovulation, hyperandrogenism and polycystic ovarian morphology.2 Current mainstay treatment for PCOS involves off-label use of combined oral hormonal contraception (COC).3 However, use of COC carries several contraindications and cautions. There is growing evidence that anti-androgen agents could be a potential effective non-hormonal treatment for hyperandrogenic symptoms of PCOS.4–6 This review focused on available randomised control trials (RCT) evaluating use of spironolactone, alone or in combination with other non-hormonal treatments for: (1) the management of hyperandrogenic symptoms of PCOS; (2) its side-effect profile; and (3) burden on patients. Materials and Methods: Following PROSPERO registration (CRD42023404914), an electronic search was performed on MEDLINE, EMBASE, PUBMED, CENTRAL and SCOPUS. Abstracts were screened against inclusion and exclusion criteria. Studies were assessed for risk of bias using standard tools, and three studies with intermediate bias risk were included in this meta-analysis. Data were analysed using STATA V13 and Open Meta-analyst software. Results and Discussion: This meta-analysis included four clinical trials.7–10 The length of these trials ranged from 6 to 24 months. They] focused on the comparison of spironolactone and metformin monotherapy, as well as the effects of combination effect on hirsutism, body mass index (BMI) and testosterone levels.Spironolactone monotherapy and metformin monotherapy did not affect testosterone levels (n=3, weighted mean (WMD) -0.06, 95% confidence interval (Cl) -0.33 to 0.20, I2 46.62%). The clinical trials showed minimal evidence to support that spironolactone improved BMI (n=3, WMD -0.22, 95% Cl -1.07 to 0.62, I2 0%) and hirsutism compared with metformin (n=3, WMD -0.27, 95% Cl -1.07 to 0.53, I2 64.44%). Additionally, spironolactone in combination with metformin did not appear to have an advantage over use of metformin in relation to BMI (n=3, WMD 0.35, 95% Cl -1.25 to 1.94, I2 84.4%), hirsutism (n=3, WMD -0.10, 95% Cl -0.66 to 0.46, I2 22.8%) and blood testosterone levels (n=3, WMD -0.35, 95% Cl -0.57 to -0.12, I2 48.4%).None of the studies reported any major adverse events with use of spironolactone.Significant heterogeneity was observed across the studies, and the overall quality of evidence in this systematic review was moderate. Our findings emphasise the lack of high-quality data on non-hormonal treatments for hyperandrogenic symptoms of PCOS. Further research is needed to explore alternative treatment options, particularly for individuals who cannot use hormonal contraceptives because of side effects or medical contraindications. Conclusion: Currently, there is a lack of randomised evidence available that supports the use of spironolactone, either alone or in combination with metformin, for women with PCOS. Additional trials are necessary to determine its benefits before routinely recommending it as a treatment.http://www.sciencedirect.com/science/article/pii/S1470211825001794 |
| spellingShingle | Irene Karderinis Yangxinrui Ma Telma Viveiros Neha Deshpande Bassel Watter Vikram Talaulikar Spironolactone and metformin combination therapy as a potential non-hormonal treatment for management of hyperandrogenic symptoms of polycystic ovarian syndrome Clinical Medicine |
| title | Spironolactone and metformin combination therapy as a potential non-hormonal treatment for management of hyperandrogenic symptoms of polycystic ovarian syndrome |
| title_full | Spironolactone and metformin combination therapy as a potential non-hormonal treatment for management of hyperandrogenic symptoms of polycystic ovarian syndrome |
| title_fullStr | Spironolactone and metformin combination therapy as a potential non-hormonal treatment for management of hyperandrogenic symptoms of polycystic ovarian syndrome |
| title_full_unstemmed | Spironolactone and metformin combination therapy as a potential non-hormonal treatment for management of hyperandrogenic symptoms of polycystic ovarian syndrome |
| title_short | Spironolactone and metformin combination therapy as a potential non-hormonal treatment for management of hyperandrogenic symptoms of polycystic ovarian syndrome |
| title_sort | spironolactone and metformin combination therapy as a potential non hormonal treatment for management of hyperandrogenic symptoms of polycystic ovarian syndrome |
| url | http://www.sciencedirect.com/science/article/pii/S1470211825001794 |
| work_keys_str_mv | AT irenekarderinis spironolactoneandmetformincombinationtherapyasapotentialnonhormonaltreatmentformanagementofhyperandrogenicsymptomsofpolycysticovariansyndrome AT yangxinruima spironolactoneandmetformincombinationtherapyasapotentialnonhormonaltreatmentformanagementofhyperandrogenicsymptomsofpolycysticovariansyndrome AT telmaviveiros spironolactoneandmetformincombinationtherapyasapotentialnonhormonaltreatmentformanagementofhyperandrogenicsymptomsofpolycysticovariansyndrome AT nehadeshpande spironolactoneandmetformincombinationtherapyasapotentialnonhormonaltreatmentformanagementofhyperandrogenicsymptomsofpolycysticovariansyndrome AT basselwatter spironolactoneandmetformincombinationtherapyasapotentialnonhormonaltreatmentformanagementofhyperandrogenicsymptomsofpolycysticovariansyndrome AT vikramtalaulikar spironolactoneandmetformincombinationtherapyasapotentialnonhormonaltreatmentformanagementofhyperandrogenicsymptomsofpolycysticovariansyndrome |