Changes in plasma müllerian-inhibiting substance and brain-derived neurotrophic factor after chemotherapy in premenopausal women

Abstract

Eight premenopausal women with cancer had blood drawn for brain-derived neurotrophic factor (BDNF) and Mullerian Inhibiting Substance (MIS) before and three months after receiving chemotherapy. Unlike MIS, BDNF levels were not reduced following chemotherapy. KeywordsOvarian reserve; chemotherapy; cancer; Mullerian inhibiting substance; Anti mullerian hormone; brain-derived neurotrophic factor Accelerated ovarian aging (1,2) and ovarian failure are common consequences of the treatment of malignant disease in women (3,4,5). At present, fertility prediction in women is imprecise. Mullerian inhibiting substance (MIS) shows particular promise in that regard (6,7). MIS is expressed in granulosa cells of follicles from initiation of growth until the early antral stages (8,9), more closely reflects ovarian reserve than do other hormones (10), and has been shown to be useful for assessing the toxicity of chemotherapeutic agents (11,12,13). Decanter et al (14) showed that MIS concentrations fell dramatically just after the start of the chemotherapy and were near their detection limit at the end of the treatment. It has also been shown that among childhood cancer survivors, MIS can be used to identify patients who are at risk for decreased fertility (15).Other markers that have been linked to ovarian function, but not ovarian reserve, are neurotrophins. Brain-derived neurotrophic factor (BDNF), one of the neurotrophin family, has been shown to be expressed in human ovaries and in human plasma (16,17,18,19 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Additionally, BDNF has been shown to be present in the follicular fluid of women with normal cycles and in the preovulatory follicles of women undergoing in vitro fertilization (17,18,20,21). Interestingly, plasma BDNF levels decrease steadily after menopause (22) and the levels tend to be lower in women with diminished ovarian reserve (23). The relationship of BDNF to chemotherapy has not been previously reported. Since BDNF decreases with age in women, we wanted to determine whether circulating BDNF is affected by chemotherapy in premenopausal women. Therefore, we measured MIS and BDNF levels in women of reproductive age, diagnosed with cancers, before and after undergoing chemotherapy. NIH Public AccessPremenopausal women who attended the Cancer Center from January 2008 till January 2009 were screened for eligibility. Women who agreed to participate were enrolled in a prospective study evaluating pre-and post-chemotherapy MIS and BDNF plasma levels. Approval for the study was obtained from the local Institutional Review Bo...

Serum AMH level as a marker of acute and long-term effects of chemotherapy on the ovarian follicular content: a systematic review

“…In this study, pre-treatment AMH levels were not different between the patients and the control population. Aslam et al [ 47 ] in a smaller case–control study had the same results. In contrast, two other studies [ 48 , 49 ] concluded that ovarian reserve seemed to be already compromised prior to chemotherapy for haematological malignancy.…”

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“…ously reported (Aslam et al, 2011;Giannini et al, 2010) but similar to women with natural cycles (Seifer et al, 2003).…”

Neurotrophins and glial cell line-derived neurotrophic factor in the ovary: physiological and pathophysiological implications

“…Lower expression levels of BDNF in women with diminished ovarian reserve may reflect their ovarian ages and a gradual decline in follicle quantity. Although many studies have demonstrated the decline in BDNF levels with advancing chronological age in women (Begliuomini et al , 2007; Ziegenhorn et al , 2007; Buyuk and Seifer, 2008), BDNF (unlike anti-Müllerian hormone) does not reflect ovarian function or serve as an indicator for cancer in women receiving chemotherapy (Aslam et al , 2011).…”