Original Paper
Chemotherapy for gestational trophoblastic tumours hastens menopause by 3 years

https://doi.org/10.1016/S0959-8049(98)00059-8Get rights and content

Abstract

Chemotherapy may induce acute ovarian failure, but in women who retain gonadal function throughout chemotherapy, the late effects upon ovarian function are unknown. A retrospective controlled survey was performed to ascertain whether chemotherapy for gestational trophoblastic tumours (GTT) results in premature menopause. Questionnaires were sent to 1,489 women diagnosed between 1971 and 1990 with GTT, including 1089 who had received chemotherapy and 400 who had not received chemotherapy (controls). Responses were obtained from 972 chemotherapy-treated patients and 327 controls. 124 women were not evaluable for menopause date as they had undergone hysterectomy as part of the treatment for GTT or had developed permanent amenorrhoea during chemotherapy. Overall, 172 women reported that they were postmenopausal, including 157 women who had received chemotherapy. The median age at menopause for the evaluable population was 50 years (range 25–56 years). The age at menopause was significantly earlier in the treated arm (median 50, range 25–56 years) than in the controls (median 53, range 40–57 years) (logrank test χ2=12.6, P=0.0004). Menopause occurred significantly earlier in women treated with combination chemotherapy (median 49, range 25–56 years) compared with single agent methotrexate (median 51, range 25–56 years) (logrank test χ2=8.3, P=0.004). However, the age at completion of chemotherapy in the treated arm did not influence the age of menopause (proportional Hazards χ2=1.99, P=0.16). Chemotherapy for GTT induces menopause 3 years earlier than it occurs in women with GTT who do not receive chemotherapy. Although the difference is statistically significant, the magnitude is modest and most women can be reassured that neither fertility nor postmenopausal osteoporosis will be greatly affected.

Introduction

There are an increasing number of women surviving long term following curative cytotoxic chemotherapy and gonadal function in these women has become a focus of concern. Many studies have focused on ovarian failure, pregnancy and risk to offspring following chemotherapy. Most women who are successfully treated with combination chemotherapy before the age of 25 years retain their normal ovarian function1, 2, 3, 4, 5. Although there have been reports of women whose menses returned after chemotherapy subsequently developing amenorrhoea, it remains unknown whether women who receive chemotherapy are at risk of an early menopause.

A large cohort of women have been treated with chemotherapy for gestational trophoblastic disease in our unit and remain in contact through monitoring assays for human chorionic gonadotrophin (hCG). A control group of women were recruited who were registered for hCG follow-up following the diagnosis of hydatidiform molar pregnancy, but who had not required chemotherapy for persistent trophoblastic disease. We undertook a postal questionnaire survey of these women enquiring about the age of menopause.

Section snippets

Patients and methods

Between 1958 and 1990, 1,377 women were treated with cytotoxic chemotherapy for gestational trophoblastic disease in our unit. Questionnaires were sent to 1,089 women known to be long-term survivors still resident in the U.K. who were on hCG monitoring follow-up. The questions were designed to detect the date of menopause and the occurrence of second malignancies and have been presented elsewhere[6]. Women were asked about their health, hospital admissions and obstetric history since they

Results

Questions regarding menopause were completed by 972 women treated with for GTT, representing 89% of questionnaires sent. Responses were obtained from 327 women in the control arm (82% of questionnaires sent). For 124 women it was not possible to evaluate the date of menopause as the women had either undergone a hysterectomy as part of their treatment for GTT or had developed permanent amenorrhoea whilst receiving chemotherapy for GTT. 42 of these women received hormone replacement therapy,

Discussion

Pretreatment fertility in men with testicular tumours and Hodgkin’s disease is impaired[13], but pretreatment amenorrhoea is uncommon in women with Hodgkin’s disease[14]. None the less, it has been suggested that premenopausal women with breast cancer are more frequently having anovulatory cycles[15]and this suggests that these women are subfertile prior to therapy. In contrast, all women with GTT who make up this cohort are fertile by definition prior to treatment.

Cytotoxic drugs disrupt

References (23)

  • K.D. Bagshawe

    Risk and prognostic factors in trophoblastic neoplasia

    Cancer

    (1976)
  • Cited by (73)

    • Classification systems in Gestational trophoblastic neoplasia - Sentiment or evidenced based?

      2017, Cancer Treatment Reviews
      Citation Excerpt :

      On the other hand, it is equally problematic to administer more intensive, toxic combination chemotherapy regimens unnecessarily to patients who would have been cured by single- agent therapy. Combination treatment is associated with a significant increase in more serious short-term effects including alopecia and myelosuppression, whilst long-term side effects include earlier menopause (brought forward by three years) and a 1.5-fold increase in the rate of secondary malignancies, particularly leukaemia [6,50–55]. Etoposide has been reported to increase the risk of secondary breast, thyroid, colorectal cancer and melanomas [55,56].

    • Mechanisms of chemotherapy-induced ovarian damage in breast cancer patients

      2017, Critical Reviews in Oncology/Hematology
      Citation Excerpt :

      Taxane administration together or after standard Doxorubicin-CPA combination in the adjuvant treatment of breast cancer worsens ovarian function (Sukumvanich et al., 2010; Yoshimura and Furuya, 2014). Antimetabolites do not directly damage DNA, so MTX, 5FU and Gemcitabine have a very limited role in ovarian toxicity even if menopause may be anticipated by MTX treatment (Bower et al., 1998). Chemotherapy seems to have a double action: amenorrhea occurs in a relatively short time, but may be reversible.

    • Rate of second primary tumors following diagnosed choriocarcinoma: A SEER analysis (1973-2010)

      2014, Gynecologic Oncology
      Citation Excerpt :

      Surgical and/or chemotherapy for CC can induce premature ovarian failure. Bower et al. [47] reported an incidence of amenorrhea after treatment for CC of more than 10%. Estrogen deficiency has been recognized to be a protective factor for breast and uterine cancers and a risk factor for colorectal and lung cancers, although the mechanism is unclear [48].

    • Gestational Trophoblastic Neoplasia

      2012, Obstetrics and Gynecology Clinics of North America
      Citation Excerpt :

      However, metastatic PSTT and ETT are relatively chemotherapy-insensitive, and cure when the disease is extrauterine is problematic. Once cured, regardless of regimen, chemotherapy patients are normally fertile, although after chemotherapy, menopause typically occurs about 3 years earlier than normal.64 Approximately 10% of patients will have a positive chest radiograph at presentation.

    View all citing articles on Scopus
    View full text