Skip to main content

Common pathophysiological mechanisms involved in luteal phase deficiency and polycystic ovary syndrome. Impact on fertility

Endocrine volume 43, pages 314–317 (2013)Cite this article

Abstract

Luteal phase deficiency (LPD) is a consequence of the corpus luteum (CL) inability to produce and preserve adequate levels of progesterone. This is clinically manifested by short menstrual cycles and infertility. Abnormal follicular development, defects in neo-angiogenesis or inadequate steroidogenesis in the lutein cells of the CL have been implicated in CL dysfunction and LPD. LPD and polycystic ovary syndrome (PCOS) are independent disorders sharing common pathophysiological profiles. Factors such as hyperinsulinemia, AMH excess, and defects in angiogenesis of CL are at the origin of both LPD and PCOS. In PCOS ovulatory cycles, infertility could result from dysfunctional CL. The aim of this review was to investigate common mechanisms of infertility in CL dysfunction and PCOS.

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

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

References

  1. G.E. Jones, Some newer aspects of management of infertility. J. Am. Med. Assoc. 141, 1123–1129 (1949)

    PubMed  Article  CAS  Google Scholar 

  2. W. Wuttke, L. Pitzel, D. Seidlova-Wuttke, B. Hinney, LH pulses and the corpus luteum: the luteal phase deficiency. Vitam. Horm. 63, 131–158 (2001)

    PubMed  Article  CAS  Google Scholar 

  3. E. Diamanti-Kandarakis, C.R. Kouli, A.T. Bergiele, F.A. Filandra, T.C. Tsianateli, G.G. Spina, E.D. Zapanti, M.I. Bartzis, A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J. Clin. Endocrinol. Metab. 84, 4006–4011 (1999)

    Article  Google Scholar 

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

    Article  Google Scholar 

  5. S.F. Witchel, S.E. Recabarren, F. González, E. Diamanti-Kandarakis, K.I. Cheang, A.J. Duleba, R.S. Legro, R. Homburg, R. Pasquali, R.A. Lobo, C.C. Zouboulis, F. Kelestimur, F. Fruzzetti, W. Futterweit, R.J. Norman, D.H. Abbott, Emerging concepts about prenatal genesis, aberrant metabolism and treatment paradigms in polycystic ovary syndrome. Endocrine (2012). doi:10.1007/s12020-012-9701-4

    PubMed  Google Scholar 

  6. M.J. De Souza, B.E. Miller, A.B. Loucks, A.A. Luciano, L.S. Pescatello, C.G. Campbell, B.L. Lasley, High frequency of luteal phase deficiency and anovulation in recreational women runners: blunted elevation in follicle-stimulating hormone observed during luteal-follicular transition. J. Clin. Endocrinol. Metab. 83, 4220–4232 (1998)

    PubMed  Article  Google Scholar 

  7. P. Miller, M. Soules, Luteal phase deficiency: pathophysiology, diagnosis and treatment. Global libr. Women’s Med. (2009). doi:10.3843/GLOWM.10327

    Google Scholar 

  8. E. Diamanti-Kandarakis, C. Christakou, E. Marinakis, Phenotypes and environmental factors: their influence in PCOS. Curr. Pharm. Des. 18, 270–282 (2012)

    PubMed  Article  CAS  Google Scholar 

  9. J.E. Nestler, Metformin for the treatment of the polycystic ovary syndrome. N. Engl. J. Med. 358, 47–54 (2008)

    PubMed  Article  CAS  Google Scholar 

  10. R. Tsutsumi, N.J. Webster, GnRH pulsatility, the pituitary response and reproductive dysfunction. Endocr. J. 56, 729–737 (2009)

    PubMed  Article  CAS  Google Scholar 

  11. R. Joseph-Horne, H. Mason, S. Batty, D. White, S. Hillier, M. Urquhart, S. Franks, Luteal phase progesterone excretion in ovulatory women with polycystic ovaries. Hum. Reprod. 17, 1459–1463 (2002)

    PubMed  Article  CAS  Google Scholar 

  12. G.F. Erickson, D.A. Magoffin, V.G. Garzo, A.P. Cheung, R.J. Chang, Granulosa cells of polycystic ovaries: are they normal or abnormal? Hum. Reprod. 7, 293–299 (1992)

    PubMed  CAS  Google Scholar 

  13. P. Fedorcsak, R. Storeng, P.O. Dale, T. Tanbo, T. Abyholm, Impaired insulin action on granulosa-lutein cells in women with polycystic ovary syndrome and insulin resistance. Gynecol. Endocrinol. 14, 327–336 (2000)

    PubMed  Article  CAS  Google Scholar 

  14. S. Rice, N. Christoforidis, C. Gadd, D. Nikolaou, L. Seyani, A. Donaldson, R. Margara, K. Hardy, S. Franks, Impaired insulin-dependent glucose metabolism in granulosa-lutein cells from anovulatory women with polycystic ovaries. Hum. Reprod. 20, 373–381 (2005)

    PubMed  Article  CAS  Google Scholar 

  15. J.M. Weiss, S. Polack, K. Diedrich, O. Ortmann, Effects of insulin on luteinizing hormone and prolactin secretion and calcium signaling in female rat pituitary cells. Arch. Gynecol. Obstet. 269, 45–50 (2003)

    PubMed  Article  CAS  Google Scholar 

  16. K.J. Meenakumari, S. Agarwal, A. Krishna, L.K. Pandey, Effects of metformin treatment on luteal phase progesterone concentration in polycystic ovary syndrome. Braz. J. Med. Biol. Res. 37, 1637–1644 (2004)

    PubMed  Article  CAS  Google Scholar 

  17. A. La Marca, F.J. Broekmans, A. Volpe, B.C. Fauser, N.S. Macklon, Anti-Müllerian hormone (AMH): what do we still need to know? Hum. Reprod. 24, 2264–2275 (2009)

    PubMed  Article  Google Scholar 

  18. A. Munsterberg, R. Lovell-Badge, Expression of the mouse anti-mullerian hormone gene suggests a role in both male and female sexual differentiation. Development 113, 613–624 (1991)

    PubMed  CAS  Google Scholar 

  19. A.P.N. Themmen, Anti-Müllerian hormone: its role in follicular growth initiation and survival and as an ovarian reserve marker. J. Natl. Cancer Inst. Monogr. 34, 18–21 (2005)

    PubMed  Article  CAS  Google Scholar 

  20. S.A. Stubbs, K. Hardy, P. Da Silva-Buttkus, J. Stark, L.J. Webber, A.M. Flanagan, A.P. Themmen, J.A. Visser, N.P. Groome, S. Franks, Anti-Müllerian hormone protein expression is reduced during the initial stages of follicle development in human polycystic ovaries. J. Clin. Endocrinol. Metab. 90, 5536–5543 (2005)

    PubMed  Article  CAS  Google Scholar 

  21. P. Pigny, E. Merlen, Y. Robert, C. Cortet-Rudelli, C. Decanter, S. Jonard, D. Dewailly, Elevated serum level of anti-mullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest. J. Clin. Endocrinol. Metab. 88, 5957–5962 (2003)

    PubMed  Article  CAS  Google Scholar 

  22. D.S. Wachs, M.S. Coffler, P.J. Malcom, R.J. Chang, Serum anti-mullerian hormone concentrations are not altered by acute administration of follicle stimulating hormone in polycystic ovary syndrome and normal women. J. Clin. Endocrinol. Metab. 92, 1871–1874 (2007)

    PubMed  Article  CAS  Google Scholar 

  23. J.H. Kim, M.M. Seibel, D.T. MacLaughlin, P.K. Donahoe, B.J. Ransil, P.A. Hametz, C.J. Richards, The inhibitory effects of müllerian-inhibiting substance on epidermal growth factor induced proliferation and progesterone production of human granulosa-luteal cells. J. Clin. Endocrinol. Metab. 75, 911–917 (1992)

    PubMed  Article  CAS  Google Scholar 

  24. L. Pellatt, S. Rice, H.D. Mason, Anti-Müllerian hormone and polycystic ovary syndrome: a mountain too high? Reproduction 139, 825–833 (2010)

    PubMed  Article  CAS  Google Scholar 

  25. M.P. Grossman, S.T. Nakajima, M.E. Fallat, Y. Siow, Müllerian-inhibiting substance inhibits cytochrome P450 aromatase activity in human granulosa lutein cell culture. Fertil. Steril. 89, 1364–1370 (2008)

    PubMed  Article  CAS  Google Scholar 

  26. L.P. Reynolds, A.T. Grazul-Bilska, D.A. Redmer, Angiogenesis in the corpus luteum. Endocrine 12, 1–9 (2001)

    Article  Google Scholar 

  27. H.M. Fraser, C. Wulff, Angiogenesis in the corpus luteum. Reprod. Biol. Endocrinol. 1, 88 (2003)

    PubMed  Article  Google Scholar 

  28. N. Ferrara, G. Frantz, J. LeCouter, L. Dillard-Telm, T. Pham, A. Draksharapu, T. Giordano, F. Peale, Differential expression of the angiogenic factor genes vascular endothelial growth factor (VEGF) and endocrine gland-derived VEGF in normal and polycystic human ovaries. Am. J. Pathol. 162, 1881–1893 (2003)

    PubMed  Article  CAS  Google Scholar 

  29. A. Galvao, S. Henriques, D. Pestka, K. Lukasik, D. Skarzynski, L.M. Mateus, G.M. Ferreira-Dias, Equine luteal function regulation may depend on the interaction between cytokines and vascular endothelial growth factor: an in vitro study. Biol. Reprod. 86, 1–9 (2012)

    Article  Google Scholar 

  30. M.B. Stanek, S.M. Borman, T.A. Molskness, J.M. Larson, R.L. Stouffer, P.E. Patton, Insulin and insulin-like growth factor stimulation of vascular endothelial growth factor production by luteinized granulosa cells: comparison between polycystic ovarian syndrome (PCOS) and non-PCOS women. J. Clin. Endocrinol. Metab. 92, 2726–2733 (2007)

    PubMed  Article  CAS  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Division of Endocrinology, First Department of Internal Medicine, Laiko General Hospital, Medical School, University of Athens, Aghiou Thoma 17 Street Goudi, Athens, Greece

    Georgios Boutzios, Maria Karalaki & Evangelia Zapanti

Authors
  1. Georgios Boutzios
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Karalaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Evangelia Zapanti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Georgios Boutzios.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Boutzios, G., Karalaki, M. & Zapanti, E. Common pathophysiological mechanisms involved in luteal phase deficiency and polycystic ovary syndrome. Impact on fertility. Endocrine 43, 314–317 (2013). https://doi.org/10.1007/s12020-012-9778-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-012-9778-9

Keywords

  • Corpus luteum
  • Luteal phase defect
  • Polycystic ovary syndrome
  • Infertility