Significant effects of mild endogenous hormonal changes in humans: considerations for low-dose testing.

We review the significant and adverse health effects that can occur with relatively small endogenous hormonal changes in pubertal and adult humans. We discuss the effects of hormonal changes that occur within normal physiologic ranges--such as the rising levels of estrogen in peripuberty, which cause growth spurts at low levels and then the fusion of epiphyses at higher levels--and the hormonal variations during the menstrual cycle and their relation to genital phenotypic changes and intercurrent disease evolution. We turn next to adaptive changes in gonadal and other functions during aging, exercise, stress, starvation, and chronic diseases, which can serve as models for the effects of exogenous, hormonally active compounds. Then we review the states of borderline hormonal imbalances such as subclinical (having few or very mild symptoms, if any) hypothyroidism or hyperthyroidism, glucose intolerance, and other endocrine conditions. Finally, we review the deleterious systemic effects of gonadal imbalance. Information stemming from clinical observations leads to the concept of "no threshold" within the endocrine system and thus illustrates the importance of considering low-dose testing for chemicals that interfere with hormonal activity. We also urge attention to more sensitive, less visible end points such as osteoporosis, increased risk for cardiovascular disease, or cognitive changes.