Biological rhythms, medication safety, and women's health.

Biological processes and functions in women are well organized in time, as evidenced by the expression of ultradian (high frequency), circadian ( approximately 24-hour), circamensual ( approximately monthly), and circannual ( approximately yearly) rhythms and by the changes that occur with menarche, reproduction, and menopause. Attributes of women's circamensual structure have been explored in depth, particularly with regard to fertility/infertility and birth control. However, the role of 24-hour and other rhythms in health, disease, and treatment has been little studied. The symptom intensity of a variety of chronic medical conditions is rhythmic, as is the risk of severe events, such as stroke and myocardial infarct (MI). Improving the safety, efficacy, and preventive qualities of medications requires the understanding of how rhythms impact drug pharmacokinetics and pharmacodynamics. The therapeutic and adverse effects of prescription and nonprescription medications widely used by women can vary markedly with the (circadian) time of administration. Circadian rhythm-dependent differences in the safety of medications are particularly relevant to pregnant women; laboratory animal studies show that the fetal toxicity of various treatments varies not only with developmental stage but also with circadian time. Rhythm-dependent differences in the actions of medications are also of great importance to perimenopausal and postmenopausal women, who are advised to ingest prescribed pharmacotherapy for osteopenia and osteoporosis in the morning to minimize the risk of adverse effects and, as a consequence, may elect to take other medications at times not recommended in the instructions for their use. Medication trials must be comprehensive and representative of women and men of different life stages, ethnicities, and likely times (morning vs. evening) of drug use.