Foreword by Sarah L. Berga

In this monograph, we explore the nuances of individualizing hormone therapy for postmenopausal women. It has been commonly assumed that all estrogens and progestins elicit comparable tissue effects. Herein, we call in question that assumption.

The goal of individualizing is to maximize benefit by minimizing risk and bother. The con of this approach is that it requires more attention to the patient’s circumstances (and thus more time and thought) in addition to an expanded knowledge base of pharmacology and molecular endocrinology. As we discover more about the tissue-specific effects of various estrogen and progestin preparations, we also develop insight into when and how to individualize therapy. A general rule of thumb in endocrinology is that physiologic hormone replacement maximizes benefit while minimizing untoward side effects. This is true for thyroid and adrenal gland replacement. For some reason, this concept has not been widely applied to the replacement of lost ovarian function. An additional hurdle has been the lack of convenient ways to mimic physiology. If replicating physiology can only be achieved by an intravenous infusion, then this approach would clearly not be feasible for most patients. Thus, in the interest of practicality, we often prescribe a pharmacologic substitute with the hope that it will get the job done in a manner that is relatively convenient.

Can we prove that physiologic hormone therapy for postmenopausal women is superior to the use of pharmacologic preparations? Not yet. Might there be pharmacologic preparations that are superior to physiologic ones?

Possibly. Are there clinical situations when mimicking physiology is prudent if for no other reason than that the patient’s medical condition existed during reproductive years and during that time she fared well? Certainly. Are there circum-stances when mimicking physiology is just not worth the effort? Probably. It will be difficult to prove that physiology is best for most postmenopausal women if we are stuck with long-term epidemiologic trials. Our ability to do comparative trials of the “best products” is limited by the fact that the “best formulations” are constantly evolving. In this sense, we might see ourselves as the victims of heightened technological wizardry. It seems that molecular endocrinology, however, might allow us to explore the hypothesis (that physiology is best) more quickly than epidemiologic approaches through use of the technique of gene microarrays or “gene chips.” If we know all the genes gated by estradiol, for instance, and put them on a “gene chip,” then we ought to be able to determine in a single assay the extent to which a given hormone preparation approximates the biologic actions of the physiologic ligand. Thus, in the relatively near future, this technology ought to permit us to determine if a new preparation is better or just new.

I hope you will keep these thoughts in mind as you read this supplement. We, the authors, have tried to explore the rationale for various approaches to hormone use by postmenopausal women. This process clearly involves educated guesswork. It is important to get used to this process, however, because so much rides on being able to wisely individualize.