Challenges and methodology for testing young healthy women in physiological studies.

Physiological responses and control of body systems differ between women and men. Moreover, within women, female gonadal hormones have important influences on organs and systems outside of reproduction. Until the NIH Revitalization Act of 1993, laboratories focused physiological research primarily on men, and this focus placed limitations on women's health care. Thus, the NIH directive to include women required scientists and physicians studying humans to consider female reproductive physiology. Even though this directive was enacted over 20 years ago, there is still a great deal of misunderstanding as to the best methods to control hormones or account for changes in internal hormone exposure in women. This discussion describes common methods investigators use to include women in physiological studies and to examine the impact of female reproductive hormone exposure for research purposes. In some cases, the goal is to control for phase of the cycle, so women are studied when the endogenous hormones should be similar to each other. When the goal of the research is to examine the effects of hormones on a physiological response, it is important to use methods that will change hormone exposure in a controlled fashion. We recommend a method that employs gonadotropin-releasing hormone (GnRH) agonist or antagonist to suppress estrogens, gonadotropins, progesterone, and androgens followed by administration of these hormones. While this method is more invasive, it is safe and is the strongest research design to examine both hormone effects within women and between women and men.