Vasomotor symptom relief versus unwanted effects: role of estrogen dosage

Recent clinical trials show that low-dose estrogen reduces the number of moderate to severe vasomotor episodes by 65%. This reduction is about midway between the 35% to 40% reduction observed with placebo and the 75% to 80% reduction observed with standard dosage. Compared with standard dosages whose effects are substantial by 4 weeks, relief with lower dosages is not maximal until 8 to 12 weeks. Women using lower dosages of estrogen experience 50% lower rates of irregular bleeding or breast tenderness compared with individuals taking standard dosages. Despite several lower dosage hormone therapy (HT) formulations being approved by the US Food and Drug Administration (FDA) and brought to market, their uptake by healthcare providers has been slow. Most women who have continued HT after reports of the Women's Health Initiative (WHI) were published take estrogen at the standard dosage; only a minority of these individuals report receiving guidance about switching to a lower dosage. The purpose of this review is to summarize the clinical trial data showing, on one hand, effects of various dosages of estrogen on vasomotor symptoms and, on the other hand, the effects of these same doses on troublesome adverse events, particularly vaginal bleeding or breast tenderness. It is time to reconsider the current estrogen dosage recommendation on the basis of symptom benefit versus symptom nuisance. Furthermore, healthcare providers need to learn how and when to prescribe lower dosages of HT to optimize patient acceptance and continuation.