Modeling Variation in the Reproductive Lifespan of Female Adolescent and Young Adult Cancer Survivors Using AMH

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Context</jats:title> <jats:p>Many female survivors of adolescent and young adult cancers (AYA survivors) have shortened reproductive lifespans. However, the timing and duration of ovarian function after cancer treatment are largely unknown.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective</jats:title> <jats:p>To model the trajectory of ovarian function over two decades following cancer treatment and evaluate how trajectories vary by treatment gonadotoxicity and age.</jats:p> </jats:sec> <jats:sec> <jats:title>Design</jats:title> <jats:p>In a prospective cohort, AYA survivors aged 18-39 at variable times since cancer treatment completion provided dried blood spots (DBS) every 6 months for up to 18 months. Anti-Müllerian hormone (AMH) levels were measured using the Ansh DBS AMH enzyme-linked immunosorbent assay. The mean AMH trajectory was modeled for the entire cohort and separately by treatment gonadotoxicity and age using functional principal components analysis.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>763 participants, mean (standard deviation) enrollment age 33.3 (4.7) and age at cancer diagnosis 25.9 (5.7) years, contributed 1905 DBS samples. The most common cancers were breast (26.9%), lymphoma (24.8%), and thyroid (18.0%). AMH trajectories differed among survivors by treatment gonadotoxicity (low, moderate, or high) (P &amp;lt; 0.001). Following low or moderately gonadotoxic treatments, AMH levels increased over 2-3 years and plateaued over 10-15 years before declining. In contrast, following highly gonadotoxic treatment, AMH levels were lower overall and declined shortly after peak at 2-3 years. Younger age at treatment was associated with higher trajectories, but a protective effect of younger age was not observed in survivors exposed to highly gonadotoxic treatments (Pinteraction &amp;lt; 0.001).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>In this large AYA survivor cohort, timing and duration of ovarian function strongly depended on treatment gonadotoxicity and age at treatment. The findings provide novel, more precise information to guide reproductive decision-making.</jats:p> </jats:sec>

Anti-Müllerian Hormone and Ovarian Reserve: Update on Assessing Ovarian Function

“…However, predicting their reproductive life span remains challenging and will require additional longitudinal studies controlled for cancer type, age of cancer diagnosis, and treatment regimen. A recent study by Su et al ( 96 ), analyzing survivors of breast cancer, thyroid cancer, and lymphoma is one of the first studies starting to address these limitations. AMH trajectories indeed differed based on the gonadotoxic effect of the treatment.…”

“…AMH trajectories indeed differed based on the gonadotoxic effect of the treatment. While treatment at younger age resulted in higher AMH trajectories, this protective effect was nullified upon treatment with high gonadotoxic agents ( 96 ).…”

The Clinical Value and Interpretation of Anti-Müllerian Hormone in Women With Cancer

“…AMH levels show this recovery. When modeling AMH in cancer survivors, levels are initially low immediately post-treatment then rise to peak between 2 and 3 years later ( 35 ). Prospective studies in women with breast cancer (median age 41), as discussed above, show both a marked fall versus pretreatment levels and minimal recovery of AMH levels over several years thereafter ( 25 ), while a comparable study in younger women with lymphoma (mean age 24) showed a clear divergence of the pattern of AMH levels by different chemotherapy regimens, with robust recovery of AMH levels in women treated with ABVD versus very limited recovery in women treated with high doses of alkylating agents ( 36 ).…”

“…A second study reported the slope of change in AMH over approximately 3 years in long-term childhood cancer survivors (median of 16 years since cancer treatment) was similar to women without cancer ( 38 ). Taken together, although AMH levels will on average be lower in a cancer survivor than a woman without cancer, there may be a long duration of relative stability with a plateau over 10 to 15 years prior to decline rather than a rapid decline for many young women who are cancer survivors ( 35 ). This is very reassuring for such patients, although additional detail is needed to confirm that this applies across the range of AMH levels.…”

The Use of AMH to Assess Ovarian Toxicity in Adolescents and Young Adults After Cancer Treatment

“…This has been demonstrated in prepubertal girls, in young adults, and in older premenopausal women, but generally in relatively small studies, particularly when prospective and mostly with less than a 5-year follow-up. The question of the longer-term function of the chemotherapy-exposed ovary therefore remains very uncertain, and it is this that Su and colleagues have investigated in a paper in the current edition of the Journal of Clinical Endocrinology and Metabolism ( 7 ). The study recruited women who had been diagnosed with cancer from the ages of 18 to 39 who were on the registries of 2 US states or were known to participating research centers.…”