Estrogen effects on neuroendocrine function: the new challenge of pulsed therapy

A growing body of evidence shows a beneficial effect of hormone replacement therapy (HRT) on climacteric symptoms, well-being, and prevention of long-term consequences of estrogen deprivation. Nevertheless, only a relatively small number of women are users, and the mean duration of treatment is only about 18-24 months. This evident reluctance to prescribe and use HRT, so-called poor compliance, is without doubt not only due to a misunderstanding of the beneficial effects of HRT but also (and mainly) due to a discordance between expectations and treatment available. In order to improve compliance and to meet the expectations of physicians and patients, there is a need for a new treatment. This new treatment has to be effective, better tolerated, reassuring for physicians and women, convenient, easy to prescribe, easy to use and also feminine. 17beta-Estradiol remains the only natural estrogen available. It is almost identical to that secreted by the ovaries, is effective on all the consequences of estrogen deprivation, and is obviously the one to choose. Research on the intimate intracellular mode of action of estrogen is progressing on a daily basis. Today, we know that there are different estrogen receptor isoforms, that the distribution of these receptors is not uniform among the tissues, and that there are different mechanisms of action: genomic and non-genomic, with rapid (seconds or minutes) or delayed (hours or days) effects. Natural hormonal stimulation of target tissues is not a continuous event over the day. Up to now, all available forms of estrogen stimulate target cells in a continuous fashion over the day and might lead to unsatisfactory reactions. Aerodiol, the first-ever pulsed estrogen therapy with its specific mode of action, a brief stimulation of estrogen receptors made possible by its unique pharmacokinetic profile and its innovative route of administration, represents a new approach in the field of HRT. Aerodiol is not only a new route of administration but really a new way to treat hormone deficiency. Data collected during phase-3 studies provide evidence that Aerodiol is at least as effective as continuous therapy such as with oral and transdermal estrogens, is better tolerated gynecologically, and may be safer. If we consider that improvement in compliance is the key issue of HRT, we have to consider women as decision-makers in this process and we have to provide them with something that meets their expectations. With two out of three women (66%) choosing Aerodiol to continue their treatment for 1 year and 85% of women continuing their treatment after 1 year, Aerodiol goes at least some way to meeting these.