Tamoxifen and Ovarian Function

PLoS One. 2013 Jun 28;8(6):e66616. doi: 10.1371/journal.pone.0066616. Print 2013.


Background: Some studies suggest that the clinical parameter "amenorrhea" is insufficient to define the menopausal status of women treated with chemotherapy or tamoxifen. In this study, we investigated and compared the ovarian function defined either by clinical or biological parameters in pre-menopausal breast cancer patients treated with tamoxifen administered as adjuvant therapy.

Materials and methods: Between 1999 and 2003, 138 premenopausal patients consecutively treated for early breast cancer were included. Sixty-eight received tamoxifen in monotherapy as the only adjuvant systemic treatment (Group I) and 70 were treated with tamoxifen after adjuvant chemotherapy (Group II). All patients had a confirmed premenopausal status based on clinical parameters and hormonal values at study entry. They were followed prospectively every 3 months for 3 years: menses data, physical examination and blood tests (LH, FSH, 17-beta-estradiol). Vaginal ultrasonography was carried out every 6 months. After 3 years, prospective evaluation was completed and monitoring of ovarian function was performed as usual in our institution (1x/year). All data were retrospectively evaluated in 2011.

Results: Three patients were excluded from the study in group I and 2 were excluded in group II. Patients were divided into 4 subgroups according to clinical data, i.e. menses patterns. These patterns were assessed by questionnaires. a: Regular menses (>10 cycles/year) b: Oligomenorrhea (5 to 9 cycles/year) c: Severe oligomenorrhea (1 to 4 cycles/year) d: Complete amenorrhea Estrogen levels did not appear to have any impact on disease-free survival rates after 3 or 8 years. FSH values were also documented and analyzed. They exhibited the same profile as estradiol values.

Conclusions: Amenorrhea is an insufficient parameter to define menopausal status in patients receiving tamoxifen. Low estradiol levels must be coupled with other biological parameters to characterize endocrine status. These data are very important for the choice of endocrine therapy.

MeSH terms

  • Adult
  • Amenorrhea / chemically induced
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / mortality
  • Carcinoma, Ductal, Breast / blood
  • Carcinoma, Ductal, Breast / drug therapy*
  • Carcinoma, Ductal, Breast / mortality
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Estradiol / blood
  • Female
  • Humans
  • Menstrual Cycle / drug effects
  • Middle Aged
  • Ovary / drug effects
  • Ovary / physiopathology*
  • Premenopause
  • Retrospective Studies
  • Tamoxifen / adverse effects
  • Tamoxifen / therapeutic use*
  • Treatment Outcome


  • Antineoplastic Agents, Hormonal
  • Tamoxifen
  • Estradiol

Grant support

The authors have no support or funding to report.