Ovarian luteinizing hormone priming preceding follicle-stimulating hormone stimulation: clinical and endocrine effects in women with long-term hypogonadotropic hypogonadism.
BACKGROUND
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.


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


METHODS
A prospective, self-controlled study was conducted at a university tertiary-care center.


METHODS
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.


METHODS
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.
Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine-University of Barcelona, 08036 Barcelona, Spain. jbalasch@ub.edu
Juan
J
Balasch
Francisco
F
Fábregues
Francisco
F
Carmona
Roser
R
Casamitjana
Manuel
M
Tena-Sempere
D000328:Adult; D000735:Androstenedione / Q000097:blood; D048429:Cell Size / Q000187:drug effects; D004334:Drug Administration Schedule; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage* / Q000097:blood; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000188:drug therapy*; D007986:Luteinizing Hormone / Q000008:administration & dosage* / Q000097:blood; D006080:Ovarian Follicle / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D010053:Ovary / Q000000981:diagnostic imaging / Q000187:drug effects*; D010062:Ovulation Induction / Q000379:methods*; D011994:Recombinant Proteins / Q000008:administration & dosage; D013997:Time Factors; D014463:Ultrasonography
D011994:Recombinant Proteins; D000735:Androstenedione; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone