Association of tamoxifen use and ovarian function in patients with invasive or pre-invasive breast cancer

Abstract

The impact of long-term tamoxifen therapy on ovarian function is not known. Understanding these effects will help reproductive-aged patients who desire future pregnancy make more informed decisions regarding their treatment. This is a retrospective cohort study in patients identified through the UCSF Cancer Registry and SPORE database. We enrolled women with a history of ductal carcinoma in situ (DCIS) or early stage invasive breast cancer who were premenopausal at diagnosis and did not receive chemotherapy. Menstrual histories were obtained through electronic and paper surveys. We compared the age of menopause onset and menstrual pattern changes between women who received tamoxifen (TAM) and those who did not receive tamoxifen (control). Neither group received chemotherapy. 250 subjects were included in this study (125 TAM, 125 control). Mean age of menopause onset was 51.0 for both the groups and was not associated with duration of tamoxifen use or the age at tamoxifen initiation. Menstrual pattern changes, including amenorrhea, were more frequent in the TAM group than control group (any change: 48% TAM vs. 15 % control, p < 0.001; amenorrhea: 22% TAM vs. 3% control, p < 0.001). Older age was associated with an increased risk of developing amenorrhea within 6 months of starting tamoxifen (HR 1.32, p < 0.001). Menstrual pattern changes are common in premenopausal women taking tamoxifen. Tamoxifen use in the absence of chemotherapy is not associated with an earlier age onset of menopause in patients with DCIS or invasive breast cancer and is unlikely to significantly accelerate ovarian aging.

Amenorrhea and Menopause in Patients with Breast Cancer after Chemotherapy

“…The majority of patients were receiving tamoxifen hormone therapy at the time of assessment, and it was associated with a decreased frequency of CIM. Although tamoxifen itself was unlikely to affect the ovarian reserve [25], changes in the FSH and estradiol levels after adjuvant hormone therapy have been previously reported, and in one study, tamoxifen exerted different effects according to the menopausal status, with elevated FSH in premenopausal women and decreased FSH in postmenopausal women [1526]. The mechanism underlying the influence of tamoxifen on TRA/CIM remains unclear.…”

Impact of tamoxifen therapy on fertility in breast cancer survivors

“…It is the first line agent for premenopausal women diagnosed with early breast cancer (4). Tamoxifen is considered an endocrine disruptor, and thus thought to be cytostatic rather than cytotoxic (5, 6). When taken daily for the recommended 5 years, tamoxifen has been shown to significantly improve survival in women with early breast cancer who remain premenopausal during treatment, reducing breast cancer mortality at 15-years after diagnosis by about one-third (risk ratio [RR] = 0.70, 95% confidence interval [CI]: 0.60, 0.80) compared to women who did not take tamoxifen (7).…”

Retained products of conception in hysteroscopy in a patient with breast cancer on tamoxifen

“…Menstrual pattern may change with tamoxifen, ranging from oligomenorrhoea to amenorrhoea. It appears that tamoxifen does not alter the age of menopause 12. In this case discussed, the 47-year-old woman had not yet reached menopause despite 2 years of amenorrhoea induced by tamoxifen.…”