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Ovarian Luteinizing Hormone Priming Preceding Follicle-Stimulating Hormone Stimulation: Clinical and Endocrine Effects in Women with Long-Term Hypogonadotropic Hypogonadism

Institute Clinic of Gynecology, Obstetrics, and Neonatology (J.B., F.F., F.C.) and Hormonal Laboratory (R.C.), Hospital Clínic-Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine-University of Barcelona, 08036 Barcelona, Spain; and Physiology Section, Department of Cell Biology, Physiology and Immunology, University of Córdoba, and Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III (M.T-S.), 14004 Córdoba, Spain

Address all correspondence and requests for reprints to: Juan Balasch, M.D., Institute Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clínic, C/Casanova 143, 08036 Barcelona, Spain. E-mail: jbalasch{at}ub.edu.

Context: Patients with hypogonadotropic hypogonadism (HH), who may be totally LH deficient, remain the primary clinical model for investigating the physiology of gonadotropin actions on ovarian steroidogenesis and follicular development.

Objectives: Our objective was to investigate the effects of LH pretreatment on subsequent ovarian stimulation with FSH in longstanding HH women.

Design and Setting: A prospective, self-controlled study was conducted at a university tertiary-care center.

Patients and Interventions: Eight HH women (six idiopathic, two surgical) underwent ovarian stimulation with recombinant human (rh)FSH preceded or not by rhLH administration in two separate cycles. In one additional patient with idiopathic HH, pretreatment was conducted with recombinant human chorionic gonadotropin (rhCG) instead of rhLH.

Main Outcome Measures: Follicular development and serum hormone concentrations throughout LH-FSH and FSH treatment cycles were assessed.

Results: Pretreatment with rhLH significantly decreased the mean threshold (daily effective) FSH dose and tended to lower the total amount of FSH required to induce follicular maturation in association with appropriate serum estradiol levels and endometrial thickness. Unexpectedly, in HH women retaining functional pituitary tissue, pretreatment with rhLH evoked a consistent elevation of serum LH levels during FSH administration, an effect that was also induced, even at higher magnitude, by pretreatment with rhCG.

Conclusions: In addition to changes in FSH requirements for follicular maturation, pretreatment with rhLH/rhCG evoked unambiguous elevations in serum levels of endogenous LH during FSH treatment in HH patients with preserved pituitary function. This is suggestive of a novel regulatory loop of LH secretion involving gonadotropin-stimulated ovarian factors whose nature and physiological relevance are yet to be disclosed, ovarian-derived kisspeptins being appealing candidates.

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