Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder and the main cause of infertility in women of reproductive age. Affected women suffer from insulin resistance and present with an intense stress response. Treatment with insulin sensitizers alone and in combination is used to ameliorate the signs and symptoms associated with the disease. This study was designed to compare the endocrine and metabolic parameters as well as subjective and objective measures of stress in women with PCOS before and after treatment with acetyl-l-carnitine (ALC) and metformin plus pioglitazone.
A total of 147 women with PCOS were randomly assigned into two groups: the combo group (n = 72) received a combination of metformin, pioglitazone, and ALC (500 mg, 15 mg, and 1500 mg, respectively), twice daily; the Met + Pio group (n = 75) received metformin plus pioglitazone (500 mg, 15 mg, respectively) and placebo (citric acid plus calcium carbonate), twice daily for 12 weeks. Medications were discontinued when pregnancy was confirmed. The Perceived Stress Scale (PSS14) and Profile of Mood States (POMS) were employed as subjective measures of stress. The endocrine and metabolic functions of women with PCOS were assessed by measuring insulin, leutinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and adiponectin levels in fasting blood samples. Insulin resistance was calculated by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).
Women at baseline had significantly elevated circulating concentration of insulin and low level of adiponectin. Treatment decreased insulin in both groups; however, the combo group showed a significant decrease (p = 0.001). Serum adiponectin level was raised significantly after treatment in both groups (p < 0.001). HOMA-IR also decreased in both groups (both p < 0.001). Testosterone, FSH, and LH significantly improved in both groups. LH also decreased in both groups; however, the change was significant only in the combo (metformin plus pioglitazone plus ALC) group (p = 0.013). Interestingly, there was a significant improvement in body circumference (p < 0.001) in the combo group. The PSS scores of the patients improved significantly (p < 0.001) in the combo group. Interestingly, regular menstrual cycles were found (97.2%) in the carnitine group, but in only 12.9% of the other group.
We conclude that addition of ALC therapy is superior to metformin plus pioglitazone in ameliorating insulin resistance, polycystic ovaries, menstrual irregularities, and hypoadiponectinemia in women with PCOS.
Trial registration: clinicalTrial.gov NCT04113889. Registered 3 October, 2019. https://clinicaltrials.gov/ct2/show/NCT04113889.
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We thank the study subjects for participating in this clinical trial.
No funding or sponsorship was received for this study or publication of this article.
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Saman Tauqir and Momina Israr were involved in the execution of project. Bushra Rauf co-supervised the study and provided clinical expertise. Syed Hamid Habib and Fawad Ali Shah helped in editing and provided critical comments. Muhammad Omar Malik helped in organization of data and did the statistical analysis. Muhammad Usman and Muhammad Asif Raza helped in packaging of drug and masking. Inayat Shah, Haroon Badshah, and Ehtesham Ehtesham provided critical discussion in the manuscript. Mohsin Shah supervised, designed, executed the study and wrote the manuscript.
The authors Saman Tauqir, Momina Israr, Bushra Rauf, Muhammad Omar Malik, Syed Hamid Habib, Fawad Ali Shah, Muhammad Usman, Muhammad Asif Raza, Inayat Shah, Haroon Badshah, Ehtesham Ehtesham, and Mohsin Shah have nothing to disclose. The authors alone are responsible for the content and writing of the paper. Metformin plus pioglitazone medications (which come under the trade name of Zolid Plus) were bought from Getz Pharmaceuticals. Acetyl-l-carnitine (ALC) was purchased by Hengtai chemical Co. Ltd (Batch#10,100,420,190,605) and packed by Zenta Pharmaceutical Company. Placebo was prepared and packed in identical packaging to ALC by Zenta Pharmaceutical Company. The pharmaceutical company had no other role in the current study.
Compliance with Ethics Guidelines
All procedures involving human participants performed in this study were in accordance with the ethical standards of Khyber Medical University’s ethics committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the institution board of study and informed consent was obtained from each participants included in the study.
Available from the corresponding author on reasonable request.
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Tauqir, S., Israr, M., Rauf, B. et al. Acetyl-l-Carnitine Ameliorates Metabolic and Endocrine Alterations in Women with PCOS: A Double-Blind Randomized Clinical Trial. Adv Ther 38, 3842–3856 (2021). https://doi.org/10.1007/s12325-021-01789-5