Skip to main content

Effect of amlodipine on blood flow of preovulatory follicle in women with clomiphene resistant polycystic ovaries: a randomized controlled trial



To detect whether amlodipine could increase pre-ovulatory follicular blood flow, thus enhancing ovulation and creating a better chance of conception in women with PCOS.


165 women were screened of which 124 were qualified and women were equally randomized to 62 receiving clomiphene citrate and amlodipine and 62 receiving clomiphene citrate and placebo. The primary outcome was to detect if amlodipine can improve pre-ovulatory follicle blood flow studied by colour and power Doppler Pulsatility index of ovarian arteries, with drug administration. The secondary outcomes were endometrial thickness and clinical pregnancy.


The mean value of the ovarian arteries Pulsatility Index was significantly lower in the amlodipine group when compared to those of the placebo group (1.36 and 1.82, respectively, with P value 0.002). Mean endometrial thickness, for all women in both groups, on the day of detecting a mature follicle was significantly higher in the amlodipine group compared to the placebo group (8.99 and 7.0, respectively, with P value 0.003), and clinical pregnancy increased from 11% to 37% in the amlodipine group compared to the placebo group.


Amlodipine improves ovarian blood flow and increases the chances of conception.

Trial registration

Pan African Clinical Trial Registry ( Trial No: PAC TR201708002485292.

This is a preview of subscription content, access via your institution.


  1. Adams J, Polson DW, Franks S (1986) Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism. Br Med J Clin Res Ed 293(6543):355–359

    Article  CAS  Google Scholar 

  2. Panidisa D, Tziomalosb K, Papadakis E, Katsikis I (2013) Polycystic ovary syndrome. Novel insights into causesand therapy. Front Horm Res 40:128–141

    Article  Google Scholar 

  3. Christian RC, Dumesic DA, Behrenbeck T, Oberg AL, Sheedy PF, Fitzpatrick LA (2003) Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome. J Clin Endocrinol Metab 88(6):2562–2568

    Article  CAS  Google Scholar 

  4. Yildir IC, Kutluturk F, Tasliyurt T et al (2013) Insulin resistance and cardiovascular risk factors in women with PCOS who have normal glucose tolerance test. Gynecol Endocrinol 29(2):148–151

    Article  Google Scholar 

  5. Dahlgren E, Janson PO, Johansson S, Lapidus L, Oden A (1992) Polycystic ovary syndrome and risk for myocardial infarction. Evaluated from a risk factor model based on a prospective population study of women. Acta Obstet Gynecol Scand 71(8):599–604

    Article  CAS  Google Scholar 

  6. Lam P, Johnson I, Raine-Fenning N (2009) Endometrial blood flow is impaired in women with polycystic ovarian syndrome who are clinically hyperandrogenic. Ultrasound Obstet Gynecol 34:326–334

    Article  CAS  Google Scholar 

  7. Ferreira A, Pires C, Moron A, Araujo JE, Traina E, Mattar R (2007) Doppler assessment of uterine blood flow in recurrent pregnancy loss. Int J Gynaecol Obstet 98:115–119

    Article  CAS  Google Scholar 

  8. Cocksedge KA, Saravelos SH, Wang Q, Tuckerman E, Laird SM, Li TC (2008) Does free androgen index predict subsequent pregnancy outcome in women with recurrent miscarriage? Hum Reprod 23:797–802

    Article  CAS  Google Scholar 

  9. Dolz M, Osborne NG, Javier Blanes J et al (1999) Polycystic ovarian syndrome: assessment with colour Doppler angiography and three-dimensional ultrasonography American Institute of Ultrasound in Medicine. J Ultrasound Med 18:303–313

    Article  CAS  Google Scholar 

  10. Loverro G, Vicino M, Lorusso F, Vimercati A, Greco P, Selvaggi L (2001) Polycystic ovary syndrome: relationship between insulin sensitivity, sex hormone levels and ovarian stromal blood flow. Gynecol Endocrinol 15(2):142–149

    PubMed  CAS  Google Scholar 

  11. Cameron I, Campbell S (1998) Nitric oxide in the endometrium. Hum Reprod Update 4:565–569

    Article  CAS  Google Scholar 

  12. Ota H, Igarashi S, Hatazawa J, Tanaka T (1998) Endothelial nitric oxide synthase in the endometrium during the menstrual cycle in patients with endometriosis an adenomyosis. Fertil Steril 69:303–308

    Article  CAS  Google Scholar 

  13. Takasaki A, Tamura H, Miwa I, Taketani T, Shimamura K, Sugino N (2010) Endometrial growth and uterine blood flow: a pilot study for improving endometrial thickness in the patients with a thin endometrium. Fertil Steril 93(6):1851–1858

    Article  CAS  Google Scholar 

  14. Jr Moreira SG, Brannigan RE, Spitz A, Francisco J, Orejuela FJ, Lipshultz LI, Kim ED (2000) Side-effect profile of sildenafil citrate (Viagra) in clinical practice. Urol J 56(3):474–476

    Article  Google Scholar 

  15. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group (2008) Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod 23:462–477

    Article  Google Scholar 

  16. Brown J, Farquhar C, Beck J, Boothroyd C, Hughes E (2009) Clomiphene and anti-oestrogens for ovulation induction in PCOS. Cochrane database. Syst Rev 4:CD002249

    Google Scholar 

  17. Johnson NP (2014) Metformin use in women with polycystic ovary syndrome. Ann Transl Med 2(6):56

    PubMed  PubMed Central  Google Scholar 

  18. The Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19:41–47

    Article  Google Scholar 

  19. Pfizer Canada Inc. Submission Control Number: 206420. Accessed 12 Sept 2017

  20. Calcium channel blocking drugs. Drug Information Reference ®2003

  21. Official FDA information, International Labs Inc ® 2017

  22. Zar JH (1984) Bio statistical analysis, 2nd edn. Prentice-Hall, Englewood Cliffs

    Google Scholar 

  23. Hintze J (2011) PASS 11 Kaysville, Utah, USA. NCSS, LLC

  24. Fetih AN, Habib DM, Abdelaal II, Hussein M, Fetih GN, Othman E (2017) Adding sildenafil vaginal gel to clomiphene citrate in infertile women with prior clomiphene citrate failure due to thin endometrium: a prospective self-controlled clinical trial. Facts Views Vis Obgyn 9(1):21–27

    PubMed  PubMed Central  CAS  Google Scholar 

  25. Soliman GM, Fetih G, Abbas AM (2017) Thermosensitive bioadhesive gels for the vaginal delivery of sildenafil citrate: in vitro characterization and clinical evaluation in women using clomiphene citrate for induction of ovulation. Drug Dev Ind Pharm 43(3):399–408. (Epub 2016 Nov 14)

    Article  PubMed  CAS  Google Scholar 

  26. Sher G, Fisch JD (2000) Vaginal sildenafil (Viagra). A preliminary report of a novel method to improve uterine artery blood flow and endometrial development in patients undergoing IVF. Hum Reprod 15:806–809

    Article  CAS  Google Scholar 

  27. Moretto MF, Lopez J, Negro-Vilar A (1993) Nitric oxide regulates luteinizing hormone-releasing hormone secretion. Endocrinology 133:2399–2402

    Article  CAS  Google Scholar 

  28. Moncada S, Higgs EA (1993) The l-arginine-nitric oxide pathway regulates luteinizing hormone-releasing hormone secretion. Endocrinol N Engl J Med 329:2002–2012

    Article  CAS  Google Scholar 

  29. Palmer RMJ, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nat Lond 327:524–526

    Article  CAS  Google Scholar 

  30. Ledee-Bataille N, Olivennes F, Lefaix JL, Chaouat G, Frydman R, Delanian S (2002) Combined treatment by pentoxifylline and tocopherol for recipient women with a thin endometrium enrolled in an oocyte donation programme. Hum Reprod 17:1249–2125

    Article  CAS  Google Scholar 

  31. (2017) Amlodipine pregnancy and breastfeeding warnings. Accessed 22 Aug 2017

  32. Ahn HK, Nava-Ocampo AA, Han JY, Choi JS, Chung JH, Yang JH, Koong MK, Park CT (2007) Exposure to amlodipine in the first trimester of pregnancy and during breastfeeding. Hypertens Pregnancy 26(2):179–187

    Article  CAS  Google Scholar 

  33. Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Devereaux PJ, Elbourne D, Egger M, Altman DG (2010) CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ 340:c869

    Article  Google Scholar 

Download references



Author information

Authors and Affiliations


Corresponding author

Correspondence to Haitham A. Torky.

Ethics declarations

Conflict of interest

The authors report that they neither have a conflict of interest nor received any financial support for this work.

Ethical approval

The study results are presented following the Consolidated Standards of Reporting Trials (CONSORT) criteria [33].

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Torky, H.A., Shata, A., Ahmad, A.M. et al. Effect of amlodipine on blood flow of preovulatory follicle in women with clomiphene resistant polycystic ovaries: a randomized controlled trial. Arch Gynecol Obstet 301, 845–850 (2020).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • Infertility
  • Amlodipine
  • Pre-ovulatory follicle
  • Clomiphene
  • Doppler ultrasonography