Uses of anti-Müllerian hormone (AMH) measurement before and after cancer treatment in women

Highlights

• Anti-Müllerian hormone (AMH) is produced by growing ovarian follicles and may be reduced after cancer therapies.

• The degree of fall is related to the gonadal toxicity of the treatment.

• Post-treatment AMH production may predict remaining reproductive lifespan.

• Pre-treatment AMH can predict POI or ongoing ovarian activity after treatment.

• AMH may also be of value in assessing ovarian function in prepubertal girls after cancer treatments.

Abstract

There is a growing body of evidence supporting the use of anti-Müllerian hormone (AMH) serum levels as a biomarker of the growing follicle pool, in turn taken to reflect the ovarian reserve, in patients being treated for cancer. Many cancer therapies are gonadotoxic, often inducing premature ovarian insufficiency (POI) and thus rendering such patients infertile. The degree of ovariotoxicity is related to the type of treatment, dosage and patient's age. As survival rates from cancer improve, post-treatment reproductive health is becoming increasingly important to affected girls and women of reproductive age to allow them to have biologically-related children. AMH levels taken post-treatment may be able to guide advice regarding remaining reproductive lifespan and aid decision-making on suitable adjuvant hormonal treatments such as in hormone receptor-positive breast cancer. Furthermore, pre-treatment AMH levels are now shown to be predictive of long-term ovarian function. The development of prognostic scoring and classification methods including the use of pre-treatment AMH, as well as other patient factors including age, to determine the likelihood of return of menses may allow better individualisation of advice regarding the use of fertility preservation strategies prior to commencing cancer treatment. AMH may also be a useful marker of cancer therapy-related ovarian damage in pre-pubertal children, although there are very limited data on the relationship between AMH and the ovarian reserve in children and adolescents. AMH is proving to be of increasing value in assessing ovarian function and advising patients before and after cancer treatment.

Introduction

The essential role of anti-Müllerian hormone (AMH) during embryogenesis has long been known. However, its value as a measure of the growing follicle pool, recently suggested to be termed the ‘ovulatory potential’ [1] and, indirectly, of the ovarian reserve in females of reproductive age and perhaps also pre-pubertal girls has only been discovered and explored relatively recently (reviewed in [2]). The value of a reliable serum biomarker of ovarian reserve would be of especial importance in the field of oncofertility, when young girls and women of reproductive age are required to undergo life-saving but gonadotoxic treatment for their cancer. With improving survival rates from nearly all forms of cancer, reproductive health after cancer therapy is becoming a major quality of life issue for many young girls and women [3]. Societal changes have led to women delaying childbirth, meaning increasing numbers of female cancer sufferers are nulliparous or yet to complete their family at the time of diagnosis. AMH measurement in women who have already undergone treatment, perhaps as children, may allow clinicians to provide guidance as to remaining reproductive lifespan, and perhaps regarding timing of childbearing. Perhaps more crucial, however, is the ability to improve prediction of the impact of cancer treatment on the individual woman, helping guide patients to decide whether to undergo fertility preservation procedures prior to treatment. It is becoming clear that AMH could have a key role in helping patients and clinicians to make this decision by allowing an individualised approach. This review will therefore explore the effect of chemo- and radiotherapy on the ovary and consider when, and why, measuring AMH is appropriate in women who have to undergo cancer therapy.