Recombinant human leptin in women with hypothalamic amenorrhea.
paper
Cited
Public
Unavailable
- Authors
- Welt, Corrine K; Chan, Jean L; Bullen, John; Murphy, Robyn; Smith, Patricia; DePaoli, Alex M; Karalis, Aspasia; Mantzoros, Christos S
- Year
- 2004
- Journal
- The New England journal of medicine
- PMID
- 15342807
- DOI
- 10.1056/NEJMoa040388
BACKGROUND: Disruptions in hypothalamic-gonadal and other endocrine axes due to energy deficits are associated with low levels of the adipocyte-secreted hormone leptin and may result in hypothalamic amenorrhea. We hypothesized that exogenous recombinant leptin replacement would improve reproductive and neuroendocrine function in women with hypothalamic amenorrhea. METHODS: Eight women with hypothalamic amenorrhea due to strenuous exercise or low weight were studied for one month before receiving recombinant human leptin and then while receiving treatment for up to three months. Six control subjects with hypothalamic amenorrhea received no treatment and were studied for a mean (+/-SD) of 8.5+/-8.1 months. RESULTS: Luteinizing hormone (LH) pulsatility, body weight, ovarian variables, and hormone levels did not change significantly over time in the controls and during a one-month control period before recombinant leptin therapy in the treated subjects. In contrast, recombinant leptin treatment increased mean LH levels and LH pulse frequency after two weeks and increased maximal follicular diameter, the number of dominant follicles, ovarian volume, and estradiol levels over a period of three months. Three patients had an ovulatory menstrual cycle (P<0.05 for the comparison with an expected rate of spontaneous ovulation of 10 percent); two others had preovulatory follicular development and withdrawal bleeding during treatment (P<0.05). Recombinant leptin significantly increased levels of free triiodothyronine, free thyroxine, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, bone alkaline phosphatase, and osteocalcin but not cortisol, corticotropin, or urinary N-telopeptide. CONCLUSIONS: Leptin administration for the relative leptin deficiency in women with hypothalamic amenorrhea appears to improve reproductive, thyroid, and growth hormone axes and markers of bone formation, suggesting that leptin, a peripheral signal reflecting the adequacy of energy stores, is required for normal reproductive and neuroendocrine function.
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| Chemerin is expressed mainly in pancreas and liver, is regulated by energy deprivation, and lacks day/night variation in humans. | Chamberland JP et al. | β | 2013 | β |
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| An age-dependent interaction with leptin unmasks ghrelin's bone-protective effects. | van der Velde M et al. | β | 2012 | β |
| A potential mechanism for the sexual dimorphism in the onset of puberty and incidence of idiopathic central precocious puberty in children: sex-specific kisspeptin as an integrator of puberty signals. | Bianco SD | β | 2012 | β |
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| Genetics of isolated hypogonadotropic hypogonadism: role of GnRH receptor and other genes. | Beate K et al. | β | 2012 | β |
| Higher ghrelin and lower leptin secretion are associated with lower LH secretion in young amenorrheic athletes compared with eumenorrheic athletes and controls. | Ackerman KE et al. | β | 2012 | β |
| Hypogonadism in male cancer patients. | Burney BO et al. | β | 2012 | β |
| Insulin resistance is a sufficient basis for hyperandrogenism in lipodystrophic women with polycystic ovarian syndrome. | Lungu AO et al. | β | 2012 | β |
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| Leptin as a modulator of neuroendocrine function in humans. | Khan SM et al. | β | 2012 | β |
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| Leptin revisited: its mechanism of action and potential for treating diabetes. | Coppari R et al. | β | 2012 | β |
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| Possible factors for altered energy balance across the menstrual cycle: a closer look at the severity of PMS, reward driven behaviors and leptin variations. | McNeil J et al. | β | 2012 | β |
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| Serum leptin and ghrelin levels in women with polycystic ovary syndrome: correlation with anthropometric, metabolic, and endocrine parameters. | Houjeghani S et al. | β | 2012 | β |
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| Syndromic insulin resistance: models for the therapeutic basis of the metabolic syndrome and other targets of insulin resistance. | Gorden P et al. | β | 2012 | β |
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| The female athlete triad. | Nazem TG et al. | β | 2012 | β |
| The impairment of reproduction in db/db mice is not mediated by intraovarian defective leptin signaling. | Zhang Y et al. | β | 2012 | β |
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| The source of leptin, but not leptin depletion in response to food restriction, changes during early pregnancy in mice. | Schlitt JM et al. | β | 2012 | β |
| Adipocytokines, gut hormones and growth factors in anorexia nervosa. | Kowalska I et al. | β | 2011 | β |
| Adolescent oligomenorrhea in a biracial schoolgirl cohort: a simple clinical parameter predicting impaired fasting glucose plus type 2 diabetes mellitus, insulin, glucose, insulin resistance, and centripetal obesity from age 19 to 25 years. | Morrison JA et al. | β | 2011 | β |
| A genetic basis for functional hypothalamic amenorrhea. | Caronia LM et al. | β | 2011 | β |
| Altered multihormone synchrony in obese patients with polycystic ovary syndrome. | Roelfsema F et al. | β | 2011 | β |
| Analysis of stress fractures in athletes based on our clinical experience. | Iwamoto J et al. | β | 2011 | β |
| Beyond Leptin: Emerging Candidates for the Integration of Metabolic and Reproductive Function during Negative Energy Balance. | True C et al. | β | 2011 | β |
| Bone metabolism in adolescents with anorexia nervosa. | Misra M et al. | β | 2011 | β |
| Bone mineral density accrual determines energy expenditure with refeeding in anorexia nervosa and supersedes return of menses. | Sum M et al. | β | 2011 | β |
| Circulating leptin concentrations do not distinguish menstrual status in exercising women. | Corr M et al. | β | 2011 | β |
| Circulating vaspin and visfatin are not affected by acute or chronic energy deficiency or leptin administration in humans. | Kang ES et al. | β | 2011 | β |
| Cross-Talk between Metabolism and Reproduction: The Role of POMC and SF1 Neurons. | Xu Y et al. | β | 2011 | β |
| Effect of food restriction and intense physical training on estrous cyclicity and plasma leptin concentrations in rats. | Dos Santos ZA et al. | β | 2011 | β |
| Effects of leptin and adiponectin on pancreatic Ξ²-cell function. | Lee YH et al. | β | 2011 | β |
| Efficacy of metreleptin in obese patients with type 2 diabetes: cellular and molecular pathways underlying leptin tolerance. | Moon HS et al. | β | 2011 | β |
| Endocrine dysregulation in anorexia nervosa update. | Miller KK | β | 2011 | β |
| Endocrine manifestations of eating disorders. | Warren MP | β | 2011 | β |
| Energy deprivation alters in a leptin- and cortisol-independent manner circulating levels of activin A and follistatin but not myostatin in healthy males. | Vamvini MT et al. | β | 2011 | β |
| Etiology and treatment of hypogonadism in adolescents. | Viswanathan V et al. | β | 2011 | β |
| Genetic basis and variable phenotypic expression of Kallmann syndrome: towards a unifying theory. | Mitchell AL et al. | β | 2011 | β |
| Hypothalamic sites of leptin action linking metabolism and reproduction. | Donato J et al. | β | 2011 | β |
| Intrafollicular and serum levels of leptin during in vitro fertilization cycles: comparison between the effects of recombinant follicle-stimulating hormones and human menopausal gonadotrophin. | Almog B et al. | β | 2011 | β |
| Leptin administered in physiological or pharmacological doses does not regulate circulating angiogenesis factors in humans. | Aronis KN et al. | β | 2011 | β |
| Leptin administration does not prevent the bone mineral metabolism changes induced by weight loss. | Conroy R et al. | β | 2011 | β |
| Leptin administration to overweight and obese subjects for 6 months increases free leptin concentrations but does not alter circulating hormones of the thyroid and IGF axes during weight loss induced by a mild hypocaloric diet. | Shetty GK et al. | β | 2011 | β |
| Leptin and the brain. | Chowen JA et al. | β | 2011 | β |
| Leptin and the regulation of body weigh. | Friedman JM | β | 2011 | β |
| Leptin and the skeleton-where is the fat? | Gordon CM | β | 2011 | β |
| Leptin in human physiology and pathophysiology. | Mantzoros CS et al. | β | 2011 | β |
| Leptin is an effective treatment for hypothalamic amenorrhea. | Chou SH et al. | β | 2011 | β |
| Leptin is not the critical signal for kisspeptin or luteinising hormone restoration during exit from negative energy balance. | True C et al. | β | 2011 | β |
| Leptin's effect on puberty in mice is relayed by the ventral premammillary nucleus and does not require signaling in Kiss1 neurons. | Donato J et al. | β | 2011 | β |
| Leptin treatment reduces body fat but does not affect lean body mass or the myostatin-follistatin-activin axis in lean hypoleptinemic women. | Brinkoetter M et al. | β | 2011 | β |
| Long-term metreleptin treatment increases bone mineral density and content at the lumbar spine of lean hypoleptinemic women. | Sienkiewicz E et al. | β | 2011 | β |
| Menstrual function in sports. | Roupas ND et al. | β | 2011 | β |
| Normal pubertal development: part II: clinical aspects of puberty. | Bordini B et al. | β | 2011 | β |
| Novel strategy for the use of leptin for obesity therapy. | Tam CS et al. | β | 2011 | β |
| Nutrition and human health from a sex-gender perspective. | Marino M et al. | β | 2011 | β |
| Obstacles in the optimization of bone health outcomes in the female athlete triad. | Ducher G et al. | β | 2011 | β |
| Patterns of corpora lutea growth and progesterone secretion in sows with thrifty genotype and leptin resistance due to leptin receptor gene polymorphisms (Iberian pig). | Gonzalez-AΓ±over P et al. | β | 2011 | β |
| Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa. | Misra M et al. | β | 2011 | β |
| Preadipocyte factor-1 levels are higher in women with hypothalamic amenorrhea and are associated with bone mineral content and bone mineral density through a mechanism independent of leptin. | Aronis KN et al. | β | 2011 | β |
| Preovulatory follicle dynamics and ovulatory efficiency in sows with thrifty genotype and leptin resistance due to leptin receptor gene polymorphisms (Iberian pig). | Gonzalez-AΓ±over P et al. | β | 2011 | β |
| Repositioning leptin as a therapy for Alzheimer's disease. | Johnston JM et al. | β | 2011 | β |
| Screening for anorexia nervosa via measurement of serum leptin levels. | FΓΆcker M et al. | β | 2011 | β |
| Short-term energy deprivation alters activin a and follistatin but not inhibin B levels of lean healthy women in a leptin-independent manner. | Moragianni VA et al. | β | 2011 | β |
| The acute effects of leptin require PI3K signaling in the hypothalamic ventral premammillary nucleus. | Williams KW et al. | β | 2011 | β |
| The neuroendocrine basis of anorexia nervosa and its impact on bone metabolism. | Misra M et al. | β | 2011 | β |
| The ventral premammillary nucleus links metabolic cues and reproduction. | Donato J et al. | β | 2011 | β |
| Adaptive thermogenesis in humans. | Rosenbaum M et al. | β | 2010 | β |
| Adipose tissue and reproduction in women. | Bohler H et al. | β | 2010 | β |
| Advanced onset of puberty in gilts of thrifty genotype (Iberian pig). | Gonzalez-AΓ±over P et al. | β | 2010 | β |
| Anorexia, bulimia, and the female athlete triad: evaluation and management. | Mendelsohn FA et al. | β | 2010 | β |
| Anorexia nervosa, osteoporosis and circulating leptin: the missing link. | Legroux-GΓ©rot I et al. | β | 2010 | β |
| Brain imaging studies of appetite in the context of obesity and the menstrual cycle. | Van Vugt DA | β | 2010 | β |
| Cellular bioenergetics as a target for obesity therapy. | Tseng YH et al. | β | 2010 | β |
| Clinical practice. Functional hypothalamic amenorrhea. | Gordon CM | β | 2010 | β |
| Colitis causes delay in puberty in female mice out of proportion to changes in leptin and corticosterone. | DeBoer MD et al. | β | 2010 | β |
| Cross-talk between adipose and gastric leptins for the control of food intake and energy metabolism. | Cammisotto PG et al. | β | 2010 | β |
| Effects of recombinant human growth hormone in anorexia nervosa: a randomized, placebo-controlled study. | Fazeli PK et al. | β | 2010 | β |
| Efficacy of leptin therapy in the different forms of human lipodystrophy. | Chong AY et al. | β | 2010 | β |
| Evidence that obesity and androgens have independent and opposing effects on gonadotropin production from puberty to maturity. | Rosenfield RL et al. | β | 2010 | β |
| Fat and bone. | Reid IR | β | 2010 | β |
| Gonadotropin-releasing hormone fibers contact POMC neurons in the hypothalamic arcuate nucleus. | Sotonyi P et al. | β | 2010 | β |
| Influence of ghrelin and adipocytokines on bone mineral density in adolescent female athletes with amenorrhea and eumenorrheic athletes. | Russell M et al. | β | 2010 | β |
| Kisspeptins: bridging energy homeostasis and reproduction. | Castellano JM et al. | β | 2010 | β |
| Lasker lauds leptin. | Flier JS et al. | β | 2010 | β |
| Lasker lauds leptin. | Flier JS et al. | β | 2010 | β |
| Leaping for leptin: the 2010 Albert Lasker Basic Medical Research Award goes to Douglas Coleman and Jeffrey M. Friedman | β | β | 2010 | β |
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| Leptin in human physiology and therapeutics. | Dardeno TA et al. | β | 2010 | β |
| Metabolic signals in human puberty: effects of over and undernutrition. | Martos-Moreno GA et al. | β | 2010 | β |
| Narrative review: the role of leptin in human physiology: emerging clinical applications. | Kelesidis T et al. | β | 2010 | β |
| Obesity and leptin resistance: distinguishing cause from effect. | Myers MG et al. | β | 2010 | β |
| Pathophysiology of bone loss in the female athlete. | Lambrinoudaki I et al. | β | 2010 | β |
| Preadipocyte factor-1 is associated with marrow adiposity and bone mineral density in women with anorexia nervosa. | Fazeli PK et al. | β | 2010 | β |
| Predictors of menstrual resumption by patients with anorexia nervosa. | Arimura C et al. | β | 2010 | β |
| Rationale for leptin-replacement therapy for severe lipodystrophy. | Oral EA et al. | β | 2010 | β |
| Regulation of thyrotropin-releasing hormone-expressing neurons in paraventricular nucleus of the hypothalamus by signals of adiposity. | Ghamari-Langroudi M et al. | β | 2010 | β |
| Slender, older women appear to be more susceptible to nontuberculous mycobacterial lung disease. | Chan ED et al. | β | 2010 | β |
| Substantiation of ovarian effects of leptin by challenging a mouse model of obesity/type 2 diabetes. | Pallares P et al. | β | 2010 | β |
| TAC3 and TACR3 defects cause hypothalamic congenital hypogonadotropic hypogonadism in humans. | Young J et al. | β | 2010 | β |
| The anorectic and obese adolescent. | Bruni V et al. | β | 2010 | β |
| The effect of pinealectomy, melatonin and leptin hormones on ovarian follicular development in female Syrian hamsters (Mesocricetus auratus). | KarakaΕ A et al. | β | 2010 | β |
| The effect of tenofovir disoproxil fumarate on whole-body insulin sensitivity, lipids and adipokines in healthy volunteers. | Randell PA et al. | β | 2010 | β |
| The long-term clinical follow-up and natural history of men with adult-onset idiopathic hypogonadotropic hypogonadism. | Dwyer AA et al. | β | 2010 | β |
| Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. | Elks CE et al. | β | 2010 | β |
| W(h)ither metreleptin for lipodystrophy and the metabolic syndrome? | Mantzoros CS | β | 2010 | β |
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| Childhood obesity and the timing of puberty. | Ahmed ML et al. | β | 2009 | β |
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| Diagnostic issues in eating disorders and obesity. | Hebebrand J | β | 2009 | β |
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| Fat targets for skeletal health. | Kawai M et al. | β | 2009 | β |
| Is there a further acceleration in the age at onset of menarche? A cross-sectional study in 1840 school children focusing on age and bodyweight at the onset of menarche. | Bau AM et al. | β | 2009 | β |
| KiSS-1/kisspeptins and the metabolic control of reproduction: physiologic roles and putative physiopathological implications. | Castellano JM et al. | β | 2009 | β |
| Leptin: a pivotal regulator of human energy homeostasis. | Farooqi IS et al. | β | 2009 | β |
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| Focus on the fire of life. | Saris WH | β | 2004 | β |
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