Reproductive and endocrine gonadal capacity in patients treated with COPP chemotherapy for Hodgkin's disease

Abstract

Testicular and ovarian functions were assessed in 33 patients with Hodgkin's disease 1 to 17 years after cessation of COPP chemotherapy with cyclophosphamide, vincristine, procarbazine, prednisone. Diagnostic procedures consisted of hormone measurements, interviews, and semen analyses. In women serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17 beta-estradiol, progesterone, prolactin, and in men FSH, LH, 17 beta-estradiol, testosterone, and prolactin were determined. Semen analyses were performed in all men. Information concerning pregnancies, pregnancy outcome, future fertility wishes, sexual functions, menstrual pattern, and incidence of premature menopausal symptoms was ascertained by interview and questionnaire. Nineteen of 19 (100%) men showed elevated serum FSH levels between 715 and 1910 (median 1095) ng/ml and azoospermia, 1 to 11 years after therapy. Serum levels of testosterone were within normal limits in 18/19 (95%) of the men, and LH values were normal in all men. Permanent ovarian failure occurred in 8/14 (57%) women, causing infertility and premature menopausal symptoms. The incidence of ovarian failure in women over 24 years was 86% (6/7) versus 28% (2/7) in those under 24 years at the time of treatment. In women receiving estrogen replacement, incidence and severity of these symptoms were significantly reduced. Of 14 women 3 (21%) became pregnant and delivered 5 healthy children after treatment. Our results suggest irreversible sterility and normal Leydig cell function after COPP chemotherapy in all men. Drug-induced ovarian failure was age-related and caused premature menopausal symptoms, detracting from the quality of the patient's life. To reduce premature menopausal symptoms and to prevent adverse cardiovascular and metabolic late sequelae, hormonal replacement is indicated. Pregnancies ending in normal live births can be achieved after COPP chemotherapy in young women. In both men and women, serum FSH and LH levels proved to be feasible markers to determine degree and duration of endocrine and reproductive gonadal injury after chemotherapy.

Fertility in male patients with advanced Hodgkin lymphoma treated with BEACOPP: a report of the German Hodgkin Study Group (GHSG)

“…Similar results have been reported elsewhere 17,22,24 and confirm the hypothesis that spermatogonia are sensitive to chemotherapy, whereas Sertoli and Leyding cells are more resistant. 16,34 Since increased FSH serum levels have been associated with germinal epithelial damage, our findings support the hypothesis that male infertility after treatment is at least in part due to germinal epithelial damage. 22,26 Although FSH levels were elevated after treatment, there was no statistically significant correlation between FSH levels and fertility status, probably due to the small number of patients in our cohort.…”

“…Similar rates of azoospermia after treatment were also reported with older regimens such as MVPP (mechlorethamine, vinblastine, procarbazine, and prednisone; 88%; 36 of 41 patients), MOPP (86%; 25 of 29 patients), and COPP (100%; 19 of 19 patients). 16,25,26 There are some indications that fertility is more often preserved with MOPP/ABVD compared with MOPP. 27 The cumulative dose of the cytostatic drugs given seems to be one of the key determinants.…”

“…35 A significant association between FSH levels and male fertility status has also been observed by others. 16 Thus, FSH levels after treatment may be of predictive significance for fertility in patients with HL.…”

“…Chemotherapy regimens, which include alkylating agents such as cyclophosphamide and procarbazine, were particularly associated with infertility. 16,17 Interestingly, most male patients with HL were shown to have inadequate sperm quality even before treatment. 18 The issue of female fertility among patients with HL after treatment with a new BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen was recently analyzed and showed that after a median follow-up of 3.2 years, 51.4% of women receiving 8 cycles of BEACOPP escalated had continuous amenorrhea.…”

Treatment-related risk factors for premature menopause following Hodgkin lymphoma

“…10 The information on the effects of chemotherapy on early menopause, however, is still limited. Studies suffer from several shortcomings, including small sample size [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] and lack of detailed information on treatment exposures. 29,30 Although in most cases only acute gonadotoxic effects and chemotherapy-related amenorrhea have been studied rather than long-term effects on premature menopause, it can be concluded that alkylating agents are the most hazardous chemotherapeutic agents, and that gonadotoxicity is dose dependent.…”