Male reproductive function is under the control of several components whose proper coordination is important for normal fertility. Several of the components and some endpoints related to male fertility, including reproductive hormones and sperm characteristics, can be studied as indicators of fertility. The reproductive neuroendocrine axis involves the central nervous system, the anterior pituitary gland, and the testis. The hypothalamus integrates neural inputs from the central and peripheral nervous systems and regulates the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Both are secreted into the circulation in episodic bursts by the anterior pituitary gland and are necessary for normal spermatogenesis. In the testis, LH interacts with receptors on Leydig cells, where it stimulates increased testosterone synthesis. FSH and the testosterone from the Leydig cells interact with the Sertoli cells in the seminiferous tubule epithelium to regulate spermatogenesis. More detailed reviews of the male reproductive hormones can be found elsewhere (Knobil et al., 1994; Yen and Jaffe, 1991). Several agents, such as lead and dibromochloropropane, affect the neuroendocrine system and spermatogenesis (for reviews, see Bonde and Giwercman, 1995; Tas et al., 1996).

Whereas many studies have investigated the relationship between chemicals and male fertility, studies among women are sparse. Some chemicals may disrupt the female hormonal balance necessary for proper functioning. Normal menstrual-cycle functioning is also important in the risk of hormonally related diseases, such as osteopenia, breast cancer, and cardiovascular disease. Chemicals can have multiple effects on the female system, including modulation of hormone concentrations, such menstrual- or ovarian-cycle irregularities as changes in menarche and menopause, and impairment of fertility (Bretveld et al., 2006a,b). In this chapter, we discuss studies that have focused on menstrual-cycle characteristics and age of menarche or age of menopause. Studies of the association between the chemicals of interest and endometriosis are reviewed in Chapter 9.

Conclusions from VAO and Updates

The committee responsible for Veterans and Agent Orange, hereafter referred to as VAO (IOM, 1994), concluded that there was inadequate or insufficient evidence of an association between exposure to 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), TCDD, picloram, or cacodylic acid and altered sperm characteristics or infertility. Additional information available to the committees responsible for Update 1996, Update 1998, Update 2000, Update 2002, and Update 2004 did not change that finding. Reviews of the relevant studies are presented in the earlier reports. Table 7-1 summarizes the studies.

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