School of Medicine

Reproductive disorders

Premature menopause

Premature menopause or premature ovarian failure (POF), is defined as menopause occurring in women under the age of 40. POF is a common disorder, and occurs in about 1-2% of women, in some as early as their late teens and twenties. The cause of most cases of POF is unknown. A number of families exist where there is an inherited predisposition to POF that would suggest that there is an inherited defective gene. We wish to determine the molecular defects in families that have led to the development of premature menopause. We have previously found mutations in two genes in woman with POF, in the inhibin alpha gene, and the FOXL2 gene.

We are also looking at other genes that are likely to be strong candidates for the development of POF. Ascertainment of the molecular basis of POF would provide a better understanding of the reproductive processes involved. It would form the basis for a genetic test for other family members at risk of developing POF. Affected women could then make informed reproductive choices, in particular with respect to the timing of child-bearing. The most immediate concern for women with POF are the menopausal symptoms they experience, coupled with the psychological implications of these symptoms. However, longterm there are concerns about a greater risk of osteoporosis and cardiovascular disease. Eventually, an understanding of the genetic defect may allow us to return fertility to some of these women by replacing the defective molecule.

Dr Shelling set up the New Zealand Premature Menopause Support Group and continues to be involved in the group. He is also a patron of the UK based Daisy Network Premature Menopause Support Group.

New Zealand Premature Menopause Support Group

Antisperm antibodies and male infertility

Sperm antibodies can be found in up to 25% of infertile couples but are also found in approximately 10% of normal fertile couples. Thus, it is difficult to determine the contribution that these antibodies make to infertility. Part of the reason for this confusion is the poor quality of existing diagnostic tests for sperm antibodies. In collaboration with Dr Larry Chamley (Department of Obstetrics and Gynaecology) we have recently identified SPRASA, which is a highly conserved sperm protein that is the target of antisperm antibodies from infertile men.

We believe SPRASA has an essential role in fertilisation that is blocked by some antisperm antibodies. The function of SPRASA is unknown but its localisation on sperm, as well as similarities to other known proteins suggests that SPRASA may be involved in the binding of sperm to oocytes. We are focused on identifying the function of SPRASA in fertility. This will allow us to determine whether SPRASA may be a target for the manipulation of reproductive function for the purposes of contraception or fertility enhancement.