Serum androgen dynamics in young women aged 18-40 treated with chemotherapy for breast cancer: an observational, multicentric, prospective study in France

Although the deleterious impact of chemotherapy regimen used to treat women of reproductive age with breast cancer on ovarian reserve has been extensively studied, hardly anything has been reported on the effect of these protocols on theca cell function and ovarian androgen secretion. The aim of this prospective multicentric cohort study was to describe serum levels of total testosterone and androstenedione during chemotherapy and 24-month follow-up in 250 patients &lt;40 years treated for breast cancer. Mean basal levels of androstenedione and total testosterone at diagnosis were 1.68 ng/mL and 0.20 ng/mL respectively. No correlation with age was found. Serum levels of androstenedione and total testosterone rapidly decreased after chemotherapy completion, before slowly increasing and almost returning to basal levels in all patients during 2-year follow-up. In conclusion our study demonstrates a chemotherapy-induced alteration of ovarian thecal function, resulting in a significant decrease in serum androgen levels. This alteration of theca cell function adds to the well-known alteration of granulosa cell function, resulting in a global, but partly transient, ovarian failure in young women treated for breast cancer. These data bring new insight into ovarian physiology and emphasize the need for pre and post-treatment ovarian follow-up. <b>Trial registration:</b> ClinicalTrial.gov identifier NCT01114464

尽管针对育龄期乳腺癌女性的化疗方案（chemotherapy regimen）对卵巢储备（ovarian reserve）的有害影响已得到广泛研究，但此类方案对卵泡膜细胞（theca cell）功能及卵巢雄激素分泌的影响却鲜有报道。本项前瞻性多中心队列研究旨在纳入250名年龄小于40岁的乳腺癌患者，分析其化疗期间及24个月随访（follow-up）期内的血清总睾酮（total testosterone）与雄烯二酮（androstenedione）水平。确诊时，雄烯二酮与总睾酮的平均基础水平（basal levels）分别为1.68 ng/mL与0.20 ng/mL，未发现与年龄存在相关性。化疗完成（chemotherapy completion）后，患者血清雄烯二酮与总睾酮水平迅速下降，随后缓慢回升，并在2年随访期内几乎恢复至基础水平。综上，本研究证实化疗可诱导卵巢卵泡膜细胞功能异常，进而引发血清雄激素水平的显著降低。此类卵泡膜细胞功能异常，与已被广泛认知的颗粒细胞（granulosa cell）功能异常共同作用，会导致接受乳腺癌治疗的年轻女性出现全面但部分可逆的卵巢功能衰竭（ovarian failure）。本研究结果为卵巢生理学（ovarian physiology）研究提供了新视角，并强调了治疗前后开展卵巢随访的必要性。<b>试验注册：</b>美国临床试验数据库（ClinicalTrial.gov）识别号NCT01114464