Changes in markers of ovarian reserve and endocrine function in young women with breast cancer undergoing adjuvant chemotherapy.
BACKGROUND
Premenopausal women undergoing chemotherapy are at risk for amenorrhea and impaired fertility. The objective of the current study was to assess levels of mullerian inhibitory substance (MIS), estradiol (E2), follicle-stimulating hormone (FSH), and menstrual status, in women undergoing chemotherapy.


METHODS
A nested prospective cohort study was conducted in women aged <40 years with breast cancer (BC) who were undergoing adjuvant chemotherapy (n = 26). Serum MIS, FSH, and E2 were measured before chemotherapy (baseline) and at Weeks 6, 12, 36, and 52. Controls were 134 age-matched women with known fertility. Hormone levels were compared between the cases and controls at baseline. Differences between amenorrhea and age subgroups were tested using the nonparametric Wilcoxon 2-sample test using a 2-sided alpha of 0.05.


RESULTS
Subjects with BC and age-matched controls had similar baseline MIS levels (median, 0.94 ng/mL vs 0.86 ng/mL;, P > .05). Serum MIS decreased significantly at 6 weeks and remained suppressed for 52 weeks. E2 levels decreased, and FSH levels increased during chemotherapy; however, at 52 weeks, the levels returned to baseline. At 52 weeks, only 1 patient had MIS above the lower normal range, 15 had return of menstrual function, 11 had premenopausal levels of FSH, and 13 had follicular phase levels of E2. In women aged <35 years, 25% remained amenorrheic, whereas in women aged >35 years, 50% were amenorrheic. Amenorrheic and menstruating women were found to have similar MIS values at baseline and follow-up.


CONCLUSIONS
In young women with BC, chemotherapy decreases MIS rapidly and dramatically. Rapid reductions in MIS do not appear to be predictive of subsequent menstrual function. Ovarian reserve and endocrine function may be affected differently by chemotherapy.
Yu
Bo
B
Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, New York 10032, USA.
Douglas
Nataki
N
Ferin
Michel J
MJ
Nakhuda
Gary S
GS
Crew
Katherine
K
Lobo
Rogerio A
RA
Hershman
Dawn L
DL
D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D004958:Estradiol / Q000097:blood*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood*; D006801:Humans; D008598:Menstruation; D011247:Pregnancy
D015415:Biomarkers; D004958:Estradiol; D054304:Anti-Mullerian Hormone; D005640:Follicle Stimulating Hormone