Low blood lead concentration in association with infertility in women

Abstract

This study investigated the relationship between low-level lead exposure and risk of infertility in women. Study participants consisted of 64 cases recruited at a private infertility clinic and 83 control women from the postpartum clinic unit at a medical center in Kaohsiung, Taiwan. With informed consent, venous blood samples were obtained from subjects, during their early follicular phases (the 1st to 5th days of the menstrual cycle), for measuring concentrations of lead and hormones. Information on other potential risk factors associated with infertility, including reproductive history, Chinese herbal Medicine use, dairy product consumption, residential environment, and sociodemographic status, was obtained during an in-person interview. The mean blood lead level (BLL) in infertile women was significantly higher than that in controls (3.55 vs 2.78 μg/dL, P=0.007). Compared to women with BLL≦2.5 μg/dL, women with BLL>2.5 μg/dL were associated with a threefold increased risk for infertility (adjusted odds ratio=2.94, 95% confidence interval 1.18–7.34), after controlling for age, body mass index, smoking, Chinese herbal Medicine use, and irregular menstruation. Women's BLL was a significant predictor of the serum estradiol concentration also. These findings suggest an important role of very low BLL in the risk of infertility in women.

Introduction

Reproductive disorders are important health issues. The World Health Organization estimates that approximately 8% of couples, or 50–80 million people worldwide, have some forms of infertility (World Health Organization (WHO), 1987). In industrialized countries, 10–15% of married couples have had either primary or secondary infertility experiences (Hruska et al., 2000). Although both exogenous exposures and endogenous pathological disorders have been associated with infertility, a significant proportion of infertility remains unexplained.

Known as a reproductive toxicant to animals including humans, lead is one of the agents that universally affects infertility. Experimental studies based on animal models have shown that lead exposure produces a decreased fertility capacity in female mice (Pinon-Lataillade et al., 1995). Lead accumulation can induce ovarian dysfunction in mice by decreasing folliculogenesis (Taupeau et al., 2001). Exposure to lead decreases the plasma progesterone concentration by blocking the luteal function in rhesus and cynomolgus monkeys (Franks et al., 1989; Foster et al., 1996).

Two studies reported that women with elevated lead exposure from occupational settings are at increased risk of developing infertility compared with women with no such exposure (Rom, 1976; Landrigan et al., 2000). Recent epidemiological studies also found that reproductive impairments may develop in women even with low-to-moderate blood lead levels (BLL) (0–30 μg/dL), including intrauterine growth restriction (Bellinger et al., 1991; Srivastava et al., 2001), preterm delivery (Sanchez et al., 1999), and spontaneous abortion (Borja-Aburto et al., 1999; Tang and Zhu, 2003).

Some other epidemiological studies examined the possible adverse reproductive outcomes due to lead exposure in men, such as the time required for the first pregnancy (Joffe et al., 2003, Joffe et al., 1999; Apostoli et al., 2000; Sallmen et al., 2000a, Sallmen et al., 2000b; Shiau et al., 2004), the frequency of spontaneous abortion (Sharara et al., 1998), and reduced fertility because of abnormal sperm (Tas et al., 1996; Gennart et al., 1992), as surrogate markers of infertility. Compared with male infertility, it is interesting to note that few studies directly examined whether low lead exposure caused reproductive effects specific to females (Rachootin and Olsen, 1983; Sallmen et al., 1995; Guerra-Tamayo et al., 2003).

Although the time required for the first pregnancy and the experience of spontaneous abortion can be used to estimate the lead-exposure-associated female infertility, the disadvantages of using these two surrogate indices include that (a) the method excludes infertile couples and (b) recalling the previous lead exposure history may not be accurate in retrospective studies when a questionnaire is administered for past pregnancies (Baranski, 1993; Sallmen et al., 2000a, Sallmen et al., 2000b). We believe that comparing the BLL between infertile women and normal women can be an appropriate alternative to estimate the effect of low lead exposure on reproductive function. To assess this correlation, we conducted a case-control study to examine whether a low-concentration BLL could still have an association with the risk for female infertility.