Authors
Cooper GS, Savitz DA, Milikan R, Chiu Kit T.

Title
Organochlorine exposure and age at natural menopause.

Journal
Epidemiology; 2002:13(6):729-733.

Summary
Onset of natural menopause can be used as a biomarker for damage to the follicular pool or disruption of normal hormonal feedback during perimenopausal transition. Smoking has been strongly associated with a decrease of about 1-2 years in the age of natural menopause, however, other toxicants including PCBs and DDT have not been examined. Both PCBs and DDT have been implicated as endocrine disrupters with potential effects on the reproductive system and menstrual cycle. In this study, Cooper et al investigate the effects of organochlorine exposure on the age of natural menopause.

The study design used was a population-based, case-control study of women with breast cancer carried out in North Carolina (1993-1996). Breast cancer cases were 21-74 years of age, selected from the Breast Cancer study group. Controls were selected from the Division of Motor Vehicle and Medicare beneficiary lists. Approximately equal numbers of African-American and white women and equal numbers of women above and below age 50 were used for the study. Serum levels of 35 individual PCB congeners and DDT and metabolites (o,p'-DDE, p,p'-DDE) were measured for each participant with serum lipid adjustment. Onset of natural menopause (at least 12 months since last menstrual period) was determined by questionnaire. Age at natural menopause was defined as age at time of last menstrual period. Women who reported natural menopause within 1 year of their current age were classified as premenopausal. Classification of the participants was as follows: premenopausal, natural menopause, surgical menopause, other, unknown. Factors considered included age, race, education, parity, lactation, physical activity, thyroid condition, body mass index and smoking.

The results suggested that higher body burdens of DDE were associated with earlier onset of natural menopause, but no association was found with PCBs. In a study examining the effects of exposure to PCB-contaminated cooking oil (YuCheng's disease) there was no difference in menopausal status comparing exposed and unexposed women. Other estrogenic exposures, such as age at menarche and oral contraceptive use, have not been consistently associated with onset of natural menopause in previous studies. The effects of tobacco smoke exposure on menopause are believed to be mediated by binding of polycyclic aromatic hydrocarbons (PAHs) to the AhR receptor in the ovary, resulting in increased apoptosis (programmed cell death) and oocyte death. The actions of DDE on the ovary are not well known. DDE is weakly estrogenic but also acts as an anti-androgen. Animal studies have shown that androgens are associated with follicular atresia and apoptosis, however, in the rhesus monkey short-term exposure to androgens has been associated with slightly decreased apoptosis and increased follicular survival. As an anti-androgen, DDE may influence the onset of menopause by disrupting follicular development and causing apoptosis, however, further research is required to determine the mechanism of action.

One limitation of this study is the reliance on self-reporting to determine age of onset of natural menopause, although self-reporting via questionnaire or interview has been found to be fairly accurate in other studies regarding menopausal status. Another limitation was the collection of blood for organochlorine analysis at the time of the study, rather than prior to the onset of menopause. Approximately 25% of the menopausal women were 20 or more years past the age of menopausal onset. Although breast cancer and treatments may affect the age of onset of menopause, there was little difference in the age of menopausal onset between breast cancer cases and controls.

This study examined the effects of organochlorine exposure and onset of natural menopause addresses an important area in reproductive health. Few studies have addressed the effects of endocrine toxicants on the timing of natural menopause. Early menopause has been associated with increased risk of cardiovascular mortality, thereby having implications beyond the reproductive system. Further investigation is required to determine whether the association of DDE with onset of menopause, reported here, can be replicated, and the biological mechanism of DDE on ovarian function.