PRINCIPLES OF TOXICOLOGY

222 REPRODUCTIVE TOXICOLOGY
Figure 11.4 Sequence of hormonal peaks and hormone balance with concomitant follicle development during
the human female reproductive cycle. Timeline indicates number of days beginning with the first day of menses;
E—Estrogen; FSH—Follicle Stimulating Hormone; LH—Luteinizing Hormone; P—Progesterone. (Reproduced
with permission from Mattison (Ed.), “Reproductive Toxicology,” American Journal of Industrial Medicine, 4
(1983): 1–2. P. 20.)
Cigarette smoking, probably the nicotine, and alcohol are both capable of interfering with GnRH
release. Alcoholics have been observed to be unable to produce the LH surge needed for ovulation,
and tobacco use is associated with decreased estrogen levels. These observations are consistent with
irregularities of the cycle that have been associated with alcohol and tobacco use. The decreased libido
and lack of cyclicity associated with narcotics abuse may relate to the hypothalamic depression that
these compounds cause. Clearly, drugs of abuse and smoking have wide ranging physiological effects,
and their toxicity is not specifically tied to female reproductive function. However, the endocrine
actions of such compounds clearly present a mechanism by which associated reproductive impairments
could be explained.
Clomiphene citrate is an example of a compound that is used therapeutically to interfere with
the female endocrine balance. This anti-estrogen is used to hyperstimulate ovulation in infertile
women. It appears to work by increasing gonadotropin release, allowing more follicular development
to occur. The anti-estrogenic properties prevent the estrogen-mediated shut down of FSH
production. There are, however, other ramifications of the anti-estrogenic activity including
decreased luteal function and decreased ability of the uterus to establish a pregnancy. The mixture
of desired and undesired outcomes is a good example of the complex outcomes associated with
endocrine interference.