Ovarian Morphometric Changes following Cyclophosphamide Treatment

  • David R. Plowchalk
  • Donald R. Mattison


Cyclophosphamide (CP) is a bifunctional alkylating agent routinely used in the treatment of a wide variety of malignancies and immunological disorders. Although CP can be quite effective in the management of these diseases, it also causes several adverse side effects. Observations by a number of investigators show that CP acts as a potent toxicant in the female reproductive system, capable of producing transient amenorrhea or complete ovarian failure (1–3). These side effects are accompanied by a reduction in serum estrogen and progesterone levels and an increase in FSH and LH, suggesting toxicity at the level of the ovary and not at the level of the hypothalamus or pituitary (4). Indeed, many animal studies demonstrate that CP produces a time-, dose-, strain-, and species-dependent destruction of oocytes and follicles (5–7). These data, collected in rodents, suggest that primordial follicles are most sensitive to CP insult, followed by growing and antral follicles. Although such changes in follicle pools are well defined, quicker and more sensitive assays are needed to assess earlier changes occurring in the follicle complex itself and other ovarian components that may be indicative signs of ovarian toxicity. Given the dynamic nature of follicle growth and replacement, it is possible that growing and antral follicles are equally or more sensitive than primordial folheies.


Corpus Luteum Antral Follicle Primordial Follicle Antral Follicle Count Ovarian Volume 
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  1. 1.
    Warne GL, Fairley KP, Hobbs JB, Martin FR. Cyclophosphamide-induced ovarian failure. N Engl J Med 1973; 289:1159–62.PubMedCrossRefGoogle Scholar
  2. 2.
    Koyama H, Wada T, Nishizawa Y, et al. Cyclophosphamide-induced ovarian failure and its therapeutic significance in patients with breast cancer. Cancer 1977; 39:1403–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Kumar R, McEvoy J, Biggart JD, McGeown MG. Cyclophosphamide and reproductive function. Lancet 1972; June 3:1212–4.CrossRefGoogle Scholar
  4. 4.
    Dnistrian AM, Schwartz MK, Fracchia AA, et al. Endocrine consequences of CMF adjuvant therapy in premenopausal and postmenopausal breast cancer patients. Cancer 1983;51:803–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Shiromizu K, Thorgeirsson S, Mattison DR. Effect of cyclophosphamide on oocyte and follicle number in Sprague-Dawley rats, C57BL/6N and DB A/2n mice. Pediatr Pharmacol (New York) 1984; 4:213–21.Google Scholar
  6. 6.
    Mattison DR, Chang L, Thorgeirsson SS, Shiromizu K. The effects of cyclophosphamide, azathioprine, and 6-mercaptopurine on oocyte and follicle number in C57BL/6N mice. Res Commun Chem Pathol Pharmacol 1981; 31:155–61.PubMedGoogle Scholar
  7. 7.
    Jarrel J, Young Lai EV, Barr R, McMahon A, Belbeck L, O’Connell G. Ovarian toxicity of cyclophosphamide alone and in combination with ovarian irradiation in the rat. Cancer Res 1987; 47:2340–3.Google Scholar
  8. 8.
    Pedersen T, Peters H. Proposal for a classification of oocytes and follicles in the mouse ovary. J Reprod Fertil 1968; 17:555–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Mattison DR, Shiromizu K, Nightingale MS. Oocyte destruction by polycyclic aromatic hydrocarbons. Am J Ind Med 1983; 4:191–202.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • David R. Plowchalk
    • 1
    • 2
  • Donald R. Mattison
    • 1
    • 2
  1. 1.University of Arkansas for Medical SciencesLittle RockUSA
  2. 2.National Center Toxicological ResearchJeffersonUSA

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