Androgen Excess and Cancer Risk in Infertile Women

Cancer Risk Among Infertile Women With Androgen Excess or Menstrual Disorders (Including Polycystic Ovary Syndrome)

Brinton LA, Moghissi KS, Westhoff C, Lamb EJ, Scoccia B
Fertil Steril. 2010;94:1787-1792

Background

Reproductive hormones play a role in the development of certain types of cancer. The association between unopposed estrogen and the development of uterine cancer is well-known. In addition, some reproductive factors are associated with various types of cancer.^[1,2] For example, early menarche, late menopause, nulliparity, older age at first birth, and lack of contraceptive use are all associated with an increased risk for both ovarian cancer and breast cancer.

The effect of androgens on cancer formation is less studied. Androgens are overproduced in a variety of clinical conditions (eg, adrenal enzyme defect, adrenal tumors, hyperprolactinemia, thyroid dysfunction, and the polycystic ovary syndrome [PCOS]). These clinical problems are often also associated with fertility problems, mainly those involving ovulatory defects. By far the most prevalent of these disorders is PCOS, which is characterized by androgen excess, cycle irregularity, and polycystic ovaries. At least half of the patients with this disorder are obese, and many also have metabolic problems, such as insulin resistance. Women with PCOS typically have chronic anovulation; if left untreated, their risk for endometrial cancer is high.^[3] The effects of androgens on other types of cancer are less obvious. This study assessed cancer risk in women with androgen excess and menstrual irregularities.

Study Summary

Patients were identified from infertility practice databases. Follow-up information was collected from cancer registries, clinic records, and questionnaires. Data were available for 8,422 patients and 155,624 person-years of follow-up. Of the original sample, 412 women met the criteria for PCOS, 1,705 had menstrual irregularities, and 443 had androgen excess only.

Compared with the general population, women with androgen excess and/or menstrual irregularities were not at an overall increased risk for noncutaneous cancer (standardized incidence ratio [SIR], 0.99; 95% CI, 0.85-1.15). When individual types of cancer were assessed, however, the risk for breast cancer (SIR, 1.31; 95% CI, 1.05-1.62), uterine cancer (SIR, 2.02; 95% CI, 1.13-3.34), and melanoma (SIR, 1.96; 95% CI, 1.12-3.18) was increased over the rates of the general population. When women with a diagnosis of PCOS were evaluated separately, the risks for breast and uterine cancer were not increased. Risk for these types of cancer was only increased in women with primary infertility.

When women with androgen excess and/or menstrual irregularity were compared with infertile women without these disorders, the overall risk for cancer or the risk for certain individual types of cancer was not increased.

Viewpoint

Women with PCOS are at increased risk for several medical problems. Diabetes, hypertension, cardiovascular disease, and dyslipidemia are all more common in these patients. Part of the extra risk is related to the pathomechanism (insulin resistance) leading to the syndrome and part is related to obesity, which is often present in this population. Women with PCOS are often infertile, and it is known that certain types of cancer are more common in infertile women. Such women are also less likely to use contraceptive pills and therefore cannot benefit from their protective effects against ovarian and uterine cancer. Women with irregular cycles are often exposed to prolonged estrogen effects and therefore have an increased risk for uterine cancer. Breast and ovarian cancer are diagnosed more often in women who give birth later in life or do not deliver at all. Breast-feeding, however, offers some protection.

This study evaluated whether women with androgen excess and/or menstrual irregularities were at higher risk for certain types of cancer. The study population is heterogeneous because women with menstrual irregularities did not necessarily have high androgen levels and vice versa. Indeed, most patients had menstrual irregularities but did not have hyperandrogenism. The analysis restricted to smaller subgroups would not have led to meaningful results because of the small numbers of cancers. Therefore, as a result of the mixed patient population, the findings have to be interpreted carefully.

Overall, the main findings of this report are reassuring because they show that the types of cancer considered are associated with infertility itself, and the diagnosis of menstrual irregularities or androgen excess does not further increase the risk. Protection against endometrial cancer is still important for women who are obese or have oligo-ovulation. Future studies should try to answer the same questions in a more homogenous patient population to allow proper counseling and screening of at-risk women.

Abstract

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