Pharmacogenomics of LH and FSH receptors

Carlo Alviggi's lecture answers the question of why patients receiving identical gonadotropin doses show such different ovarian responses, and how the pharmacogenomics of FSH and LH receptors helps to explain and predict this variability. The focus shifts from standard protocols toward the molecular profile of the individual patient.

The analysis is built on the pharmacogenomics of FSH and the functionally linked FSH-LH system. The effect of an exogenous gonadotropin is determined not only by the administered dose but also by how a patient's genome encodes the receptors and the hormones themselves. It is at the level of ligand-receptor interaction that the differences later seen by the clinician as a good or a weak response first arise.

Particular attention is given to the classic lock-and-key model of hormone-receptor binding. Alviggi highlights its limitations: the real interaction is more complex than simple geometric complementarity, and current data point to the role of receptor conformational states and the modulating influence of LH. Recognising these limits reshapes how we interpret why the same drug behaves differently across patients.

An important section addresses the clearance and metabolism of gonadotropins, where individual variability is especially pronounced. Elimination rate and bioavailability differ between patients, so a fixed dose does not guarantee the same serum concentration or the same follicular stimulation. This pharmacokinetic layer complements the pharmacogenomic one and accounts for part of the unpredictability of cycles.

The central practical idea of the lecture is that polymorphisms of receptor and hormone genes serve as predictors of dose and response. Carrying certain FSH or LH receptor variants is associated with altered sensitivity, which may call for adjusting the starting dose or adding LH activity. This approach relies on the biology of the specific patient rather than on averaged protocol templates.