Hormone variability and hot flash experience: Results from the midlife women's health study

Objective: Hot flashes are believed to be related to hormonal changes. However, the relationship between hormonal fluctuations and hot flashes has not been studied. The objective of this study is to determine hormone measurement summaries that best explain the incidence of hot flashes in midlife women. Study design: In a cohort study of 798 midlife women over 1–7 years, women provided 4 weekly blood samples annually and completed a survey detailing life history, ongoing behaviors, and menopausal symptoms. Estradiol, progesterone, and testosterone were measured in all serum samples. Annual summary variables of each hormone were median, mean, maximum, minimum, variance, and range. The association of these values with hot flashes was assessed using multivariable logistic regression and Bayesian network analysis, controlling for smoking history and menopausal status. Main outcome measures: Hot flash incidence, severity, and frequency. Results: For most outcomes, the best-fit model included progesterone variability; increased progesterone variance or range was correlated with decreased hot flash frequency (OR = 0.82, 95% CI = 0.74–0.91) and severity (OR = 0.82, 95% CI = 0.77-0.88). In the Bayesian network model, the maximum estradiol value was negatively correlated with many outcomes (OR for hot flashes = 0.68). Relationships between progesterone variability, maximum estradiol level, maximum progesterone level, and hot flashes indicate that the effects of progesterone variance on hot flash outcomes are likely mediated through progesterone's relationship with maximum estradiol level. Conclusions: Variability of progesterone, as opposed to mean values, should be used as an indicator of risk of hot flashes in midlife women.