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Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of Kisspeptin-54. 2014

Channa N Jayasena, and Ali Abbara, and Johannes D Veldhuis, and Alexander N Comninos, and Risheka Ratnasabapathy, and Akila De Silva, and Gurjinder M K Nijher, and Zainab Ganiyu-Dada, and Amrish Mehta, and Catriona Todd, and Mohammad A Ghatei, and Stephen R Bloom, and Waljit S Dhillo
Section of Investigative Medicine (C.N.J., A.A., A.N.C., R.R., A.D.S., G.M.K.N., Z.G.-D., M.A.G., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom; and Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905; and Department of Imaging (A.M., C.T.), Imperial College Healthcare National Health Service Trust, Charing Cross Hospital, London W6 8RF, United Kingdom.

BACKGROUND Hypothalamic amenorrhea (HA) is the one of the most common causes of period loss in women of reproductive age and is associated with deficient LH pulsatility. High-dose kisspeptin-54 acutely stimulates LH secretion in women with HA, but chronic administration causes desensitization. GnRH has paradoxical effects on reproductive activity; we therefore hypothesized that a dose-dependent therapeutic window exists within which kisspeptin treatment restores the GnRH/LH pulsatility in women with HA. OBJECTIVE The aim of the study was to determine whether constant iv infusion of kisspeptin-54 temporarily increases pulsatile LH secretion in women with HA. METHODS Five patients with HA each underwent six assessments of LH pulsatility. Single-blinded continuous iv infusion of vehicle or kisspeptin-54 (0.01, 0.03, 0.10, 0.30, or 1.00 nmol/kg/h) was administered. The LH pulses were detected using blinded deconvolution. RESULTS Kisspeptin increased LH pulsatility in all patients with HA, with peak responses observed at different doses in each patient. The mean peak number of pulses during infusion of kisspeptin-54 was 3-fold higher when compared with vehicle (number of LH pulses per 8 h: 1.6 ± 0.4, vehicle; 5.0 ± 0.5, kisspeptin-54, P < .01 vs vehicle). The mean peak LH pulse secretory mass during kisspeptin-54 was 6-fold higher when compared with vehicle (LH pulse secretory mass in international units per liter: 3.92 ± 2.31, vehicle; 23.44 ± 12.59, kisspeptin-54; P < .05 vs vehicle). CONCLUSIONS Kisspeptin-54 infusion temporarily increases LH pulsatility in women with HA. Furthermore, we have determined the dose range within which kisspeptin-54 treatment increases basal and pulsatile LH secretion in women with HA. This work provides a basis for studying the potential of kisspeptin-based therapies to treat women with HA.

UI MeSH Term Description Entries
D007027 Hypothalamic Diseases Neoplastic, inflammatory, infectious, and other diseases of the hypothalamus. Clinical manifestations include appetite disorders; AUTONOMIC NERVOUS SYSTEM DISEASES; SLEEP DISORDERS; behavioral symptoms related to dysfunction of the LIMBIC SYSTEM; and neuroendocrine disorders. Froehlich's Syndrome,Hypothalamic-Neurohypophyseal Disorders,Pituitary Diencephalic Syndrome,Hypothalamic Dysfunction Syndromes,Hypothalamic Dysinhibition Syndrome,Hypothalamic Overactivity Syndrome,Hypothalamic Pseudopuberty,Hypothalamic-Adenohypophyseal Disorders,Diencephalic Syndrome, Pituitary,Diencephalic Syndromes, Pituitary,Disease, Hypothalamic,Diseases, Hypothalamic,Disorder, Hypothalamic-Adenohypophyseal,Disorder, Hypothalamic-Neurohypophyseal,Disorders, Hypothalamic-Adenohypophyseal,Disorders, Hypothalamic-Neurohypophyseal,Dysfunction Syndrome, Hypothalamic,Dysfunction Syndromes, Hypothalamic,Dysinhibition Syndrome, Hypothalamic,Dysinhibition Syndromes, Hypothalamic,Froehlich Syndrome,Froehlichs Syndrome,Hypothalamic Adenohypophyseal Disorders,Hypothalamic Disease,Hypothalamic Dysfunction Syndrome,Hypothalamic Dysinhibition Syndromes,Hypothalamic Neurohypophyseal Disorders,Hypothalamic Overactivity Syndromes,Hypothalamic Pseudopuberties,Hypothalamic-Adenohypophyseal Disorder,Hypothalamic-Neurohypophyseal Disorder,Overactivity Syndrome, Hypothalamic,Overactivity Syndromes, Hypothalamic,Pituitary Diencephalic Syndromes,Pseudopuberties, Hypothalamic,Pseudopuberty, Hypothalamic,Syndrome, Froehlich's,Syndrome, Hypothalamic Dysfunction,Syndrome, Hypothalamic Dysinhibition,Syndrome, Hypothalamic Overactivity,Syndromes, Hypothalamic Dysfunction,Syndromes, Hypothalamic Dysinhibition,Syndromes, Hypothalamic Overactivity,Syndromes, Pituitary Diencephalic
D007262 Infusions, Intravenous The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it. Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D007986 Luteinizing Hormone A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Luteinizing hormone regulates steroid production by the interstitial cells of the TESTIS and the OVARY. The preovulatory LUTEINIZING HORMONE surge in females induces OVULATION, and subsequent LUTEINIZATION of the follicle. LUTEINIZING HORMONE consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH and FSH), but the beta subunit is unique and confers its biological specificity. ICSH (Interstitial Cell Stimulating Hormone),Interstitial Cell-Stimulating Hormone,LH (Luteinizing Hormone),Lutropin,Luteoziman,Luteozyman,Hormone, Interstitial Cell-Stimulating,Hormone, Luteinizing,Interstitial Cell Stimulating Hormone
D008597 Menstrual Cycle The period from onset of one menstrual bleeding (MENSTRUATION) to the next in an ovulating woman or female primate. The menstrual cycle is regulated by endocrine interactions of the HYPOTHALAMUS; the PITUITARY GLAND; the ovaries; and the genital tract. The menstrual cycle is divided by OVULATION into two phases. Based on the endocrine status of the OVARY, there is a FOLLICULAR PHASE and a LUTEAL PHASE. Based on the response in the ENDOMETRIUM, the menstrual cycle is divided into a proliferative and a secretory phase. Endometrial Cycle,Ovarian Cycle,Cycle, Endometrial,Cycle, Menstrual,Cycle, Ovarian,Cycles, Endometrial,Cycles, Menstrual,Cycles, Ovarian,Endometrial Cycles,Menstrual Cycles,Ovarian Cycles
D011673 Pulsatile Flow Rhythmic, intermittent propagation of a fluid through a BLOOD VESSEL or piping system, in contrast to constant, smooth propagation, which produces laminar flow. Flow, Pulsating,Perfusion, Pulsatile,Flow, Pulsatile,Flows, Pulsatile,Flows, Pulsating,Perfusions, Pulsatile,Pulsatile Flows,Pulsatile Perfusion,Pulsatile Perfusions,Pulsating Flow,Pulsating Flows
D004958 Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. 17 beta-Estradiol,Estradiol-17 beta,Oestradiol,17 beta-Oestradiol,Aerodiol,Delestrogen,Estrace,Estraderm TTS,Estradiol Anhydrous,Estradiol Hemihydrate,Estradiol Hemihydrate, (17 alpha)-Isomer,Estradiol Monohydrate,Estradiol Valerate,Estradiol Valeriante,Estradiol, (+-)-Isomer,Estradiol, (-)-Isomer,Estradiol, (16 alpha,17 alpha)-Isomer,Estradiol, (16 alpha,17 beta)-Isomer,Estradiol, (17-alpha)-Isomer,Estradiol, (8 alpha,17 beta)-(+-)-Isomer,Estradiol, (8 alpha,17 beta)-Isomer,Estradiol, (9 beta,17 alpha)-Isomer,Estradiol, (9 beta,17 beta)-Isomer,Estradiol, Monosodium Salt,Estradiol, Sodium Salt,Estradiol-17 alpha,Estradiol-17beta,Ovocyclin,Progynon-Depot,Progynova,Vivelle,17 beta Estradiol,17 beta Oestradiol,Estradiol 17 alpha,Estradiol 17 beta,Estradiol 17beta,Progynon Depot
D005260 Female Females
D005640 Follicle Stimulating Hormone A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. FSH (Follicle Stimulating Hormone),Follicle-Stimulating Hormone,Follitropin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000293 Adolescent A person 13 to 18 years of age. Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths

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