Trial reportProceedings of the National Academy of Sciences of the United States of America2011
Leptin is an effective treatment for hypothalamic amenorrhea.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00130117 (Randomized, Double-blind, Placebo-controlled Trial of Human Recombinant Leptin), which is not on this map. Cited by 110 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Randomized, Double-blind, Placebo-controlled Trial of Human Recombinant Leptin (r-metHuLeptin) for the Treatment of Hypothalamic (Exercise-Induced) Amenorrhea
Who cites it
110 citing papers in PubMed, 286 citations in OpenAlex.
- Leptin Decreases Energy Expenditure Despite Increased Thyroid Hormone in Patients With Lipodystrophy.The Journal of clinical endocrinology and metabolism · 2021Trial
- Regulation of the activins-follistatins-inhibins axis by energy status: Impact on reproductive function.Metabolism: clinical and experimental · 2018Trial
- Leptin administration in physiological or pharmacological doses does not alter circulating irisin levels in humans.International journal of obesity (2005) · 2016Trial
- The effect of leptin replacement on parathyroid hormone, RANKL-osteoprotegerin axis, and Wnt inhibitors in young women with hypothalamic amenorrhea.The Journal of clinical endocrinology and metabolism · 2014Trial
- Circulating fetuin-A levels are not affected by short and long-term energy deprivation and/or by leptin administration.Metabolism: clinical and experimental · 2014Trial
- Gender dimorphism and lack of day/night variation or effects of energy deprivation on undercarboxylated osteocalcin levels in humans.Obesity (Silver Spring, Md.) · 2013Trial
- Neuroendocrine recovery initiated by cognitive behavioral therapy in women with functional hypothalamic amenorrhea: a randomized, controlled trial.Fertility and sterility · 2013Trial
- Randomized double-blind placebo-controlled study of leptin administration after gastric bypass.Obesity (Silver Spring, Md.) · 2013Trial
- Selective capacity of metreleptin administration to reconstitute CD4+ T-cell number in females with acquired hypoleptinemia.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- The effect of gonadal and adrenal steroid therapy on skeletal health in adolescents and young women with anorexia nervosa.Metabolism: clinical and experimental · 2012Trial
- Short-term energy deprivation alters activin a and follistatin but not inhibin B levels of lean healthy women in a leptin-independent manner.The Journal of clinical endocrinology and metabolism · 2011Trial
- Energy deprivation alters in a leptin- and cortisol-independent manner circulating levels of activin A and follistatin but not myostatin in healthy males.The Journal of clinical endocrinology and metabolism · 2011Trial
- 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.The Journal of clinical endocrinology and metabolism · 2011Trial
- Leptin administered in physiological or pharmacological doses does not regulate circulating angiogenesis factors in humans.Diabetologia · 2011Trial
- Leptin treatment reduces body fat but does not affect lean body mass or the myostatin-follistatin-activin axis in lean hypoleptinemic women.American journal of physiology. Endocrinology and metabolism · 2011Trial
- Circulating vaspin and visfatin are not affected by acute or chronic energy deficiency or leptin administration in humans.European journal of endocrinology · 2011Trial
- Adipose tissue as a humoral-neuronal hub in metabolic regulation.Nature reviews. Endocrinology · 2026Review
- Variation in the diagnosis and management of functional hypothalamic amenorrhea across clinical specialties: A nationwide cross-sectional survey in China.The Journal of international medical research · 2026Article
- Hypothalamic regulation of energy homeostasis: Quo vadis.Reviews in endocrine & metabolic disorders · 2026Review
- The Intimate Relationship between Adipose Tissue, Fertility, and Bone.Journal of frailty, sarcopenia and falls · 2026Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Hypothalamic amenorrhea (HA) is associated with dysfunction of the hypothalamic-pituitary-peripheral endocrine axes, leading to infertility and bone loss, and usually is caused by chronic energy deficiency secondary to strenuous exercise and/or decreased food intake. Energy deficiency also leads to hypoleptinemia, which has been proposed, on the basis of observational studies as well as an open-label study, to mediate the neuroendocrine abnormalities associated with this condition. To prove definitively a causal role of leptin in the pathogenesis of HA, we performed a randomized, double-blinded, placebo-controlled trial of human recombinant leptin (metreleptin) in replacement doses over 36 wk in women with HA. We assessed its effects on reproductive outcomes, neuroendocrine function, and bone metabolism. Leptin replacement resulted in recovery of menstruation and corrected the abnormalities in the gonadal, thyroid, growth hormone, and adrenal axes. We also demonstrated changes in markers of bone metabolism suggestive of bone formation, but no changes in bone mineral density were detected over the short duration of this study. If these data are confirmed, metreleptin administration in replacement doses to normalize circulating leptin levels may prove to be a safe and effective therapy for women with HA.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.