Gonadal Dysfunction in Patients Receiving Chemotherapy for Cancer

Abstract

Since the introduction of antineoplastic chemotherapy, lasting clinical remissions have been obtained for many patients with acute lymphoblastic leukemia, Hodgkin's disease, gestational trophoblastic tumors, and other malignancies. With this therapeutic success there have been concerns about persistent or delayed toxicities of cancer chemotherapy that may become clinically significant for long-term survivors. Gonadal toxicity and infertility occur in many men, women, and children treated with antineoplastic drugs. In this paper we review the clinical syndromes of chemotherapy-related gonadal toxicity and discuss how particular drug classes, doses, or combinations correlate with the degree of gonadal injury and with the potential for recovery of function. Further, we examine how drug effects on germ cell production and endocrine function vary with the age of the patient at the time of treatment. Finally, we comment on the need for long-term prospective studies of fertility, teratogenesis, and mutagenesis in patients receiving cancer chemotherapy.

Chemotherapy-Induced Amenorrhea and Fertility in Women Undergoing Adjuvant Treatment for Breast Cancer

“…20 Following treatment with chemotherapy, the ovaries have a decreased number of oocytes available for follicular recruitment, along with evidence of fibrosis. [6][7][8][9]21 These changes are similar to those observed in natural postmenopausal ovaries. However, the chemotherapy induces further reduction and insult to a diminished population of oocytes, which may manifest in overt ovarian failure.…”

“…The cytotoxic agent that has been most intensely studied and known to induce amenorrhea is cyclophosphamide. [6][7][8][9] Cyclophosphamide is an integral part of most of the commonly used regimens for the adjuvant treatment of breast cancer. Table 3 depicts amenorrhea rates associated with various regimens used in the adjuvant setting.…”

Risedronate Prevents Bone Loss in Breast Cancer Survivors: A 2-Year, Randomized, Double-Blind, Placebo-Controlled Clinical Trial

“…[1][2][3][4][5][6][7] The Risedronate Effect on Bone Loss in Breast Cancer (REBBeCa) trial was designed to examine the efficacy of risedronate once weekly, an oral antiresorptive therapy, in the prevention of bone loss in newly postmenopausal women with breast cancer treated with chemotherapy. 8 After 1 year, bone mass significantly increased at the spine and the hip with risedronate compared with placebo.…”

Protection of rat spermatogenic epithelium from damage induced by procarbazine chemotherapy

“…In adult males, the incidence of permanently induced azoospermia from combination chemotherapy with six or more courses of nitrogen mustard, vincristine or vinblastine, procarbazine, and prednisone (MOPP or MVPP) is 80-90% (Schilsky et al, 1980). Testicular function in prepubertal males may be partially protected from cytotoxic drugs, as evidenced by more normal gonadotropin levels and usually normal progression through puberty (Rivkees & Crawford, 1988;Sherins et al, 1978).…”

“…In clinical settings, the recovery time of marrow and gut are dose limiting; however, at the 'tolerable' dose for these acute effects, irreparable damage may be done to testicular and ovarian function. Thus, numerous reports suggest that permanent infertility may accompany curative drug therapy for neoplasia, especially Hodgkin's disease (Sherins & DeVita, 1973;Schilsky et al, 1980;Rivkees & Crawford, 1988).…”