The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
The long-term effect of recombinant methionyl human leptin therapy on hyperandrogenism and menstrual function in female and pituitary function in male and female hypoleptinemic lipodystrophic patients
Abstract
Lipodystrophy patients are hypoleptinemic and insulin resistant. Women have enlarged polycystic ovaries, hyperandrogenism, and amenorrhea. We have determined the role of correction of hypoleptinemia on these metabolic and neuroendocrine parameters. Ten females and 4 males with generalized lipodystrophy were treated with recombinant methionyl human leptin (r-metHuLeptin) in physiologic doses in an open-labeled study for a period of 12 and 8 months, respectively. In the female group, serum free testosterone decreased from 39.6 +/- 11 to 18.9 +/- 4.5 ng/dL (P < 0.01) and serum sex hormone binding globulin increased from 14 +/- 2.5 to 25 +/- 4.8 nmol/L (P < 0.02). Luteinizing hormone (LH) responses to LH releasing hormone were more robust after therapy and significantly changed in the youngest group of 3 female patients (P < 0.01). Ovarian ultrasound showed a polycystic ovarian disease pattern in all patients and did not change after therapy. Eight of the 10 patients had amenorrhea prior to therapy and all 8 developed normal menses after therapy. In the male group, serum testosterone tended to increase from 433 +/- 110 to 725 +/- 184 ng/dL (P = 0.1) and sex hormone binding globulin also increased from 18.25 +/- 2.6 to 27 +/- 1.7 nmol/L (P < 0.04) following r-metHuLeptin therapy. Serum LH response to LH releasing hormone did not show significant changes. Five additional hypoleptinemic male subjects with minimal metabolic abnormalities underwent normal pubertal development without receiving r-metHuLeptin therapy. In both genders, insulin-like growth factor increased significantly and there were no differences in growth hormone, thyroid, or adrenal hormone levels following r-metHuLeptin therapy. Glycemic parameters significantly improved after r-metHuLeptin therapy in both groups. Hypoglycemic medications were discontinued in 7 of 12 patients and dramatically reduced in 5 patients. r-metHuLeptin therapy plays an important role in insulin sensitivity. In females, it plays an additional role in normalizing menstrual function. This is likely to occur both from increasing insulin sensitivity and from restoring LH pulsatility. The persistent hypoleptinemic state in these subjects did not inhibit pubertal development.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Female patients generally had hypogonadotropic amenorrhea, as previously described (9,10).”
From Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy (2005) · cites this paper as [10]
In the citing paper
“Most female patients resumed and sustained normal menses following initiation of r-metHuLeptin”
From Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy (2005) · cites this paper as [10]
In the citing paper
“consistent with normalization of their gonadotropin axis (9,10).”
From Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy (2005) · cites this paper as [10]
In the citing paper
“R-metHuLeptin therapy led to a decrease in serum androgen levels and normal cyclic menses in women of reproductive age (9,10).”
From Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy (2005) · cites this paper as [10]
In the citing paper
“R-MetHuLeptin therapy is associated with decreased energy intake, improvements in dyslipidemia, hepatic steatosis, and insulin resistance, as well as hypothalamic regulation of the gonadal axis (9,10).”
From Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy (2005) · cites this paper as [10]
In the citing paper
“Treatment with metreleptin also has improved reproductive function in other leptin-de fi cient conditions, including congenital leptin de fi ciency (23) and lipodystrophy (26), in uncontrolled pilot studies.”
From Leptin is an effective treatment for hypothalamic amenorrhea (2011) · cites this paper as [26]
Citations
Cites
Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis
Dunaif, A. E. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.6.0318 · Cited by 2,776
Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
Minokoshi, Y., Kim, Y.-B., Peroni, O. D., Fryer, L. G. D., Müller, C., Carling, D., & Kahn, B. B. (2002) · Nature · doi:10.1038/415339a · Cited by 2,053
Farooqi, I. S., Matarese, G., Lord, G. M., Keogh, J. M., Lawrence, E., Agwu, C., Sanna, V., Jebb, S. A., Perna, F., Fontana, S., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15693 · Cited by 1,374
Self-citationLeptin-Replacement Therapy for Lipodystrophy
Oral, E. A., Simha, V., Ruiz, E., Andewelt, A., Premkumar, A., Snell, P., Wagner, A. J., DePaoli, A. M., Reitman, M. L., Taylor, S. I., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa012437 · Cited by 1,247 · cited 9×
“The second is acquired and congenital forms of lipodystrophy, characterized by insulin resistance [2], and the third is the Rabson-Mendenhall syndrome with a presumed mutation in the insulin receptor and also characterized by insulin resistance [11].”
BackgroundResultInfluentialSelf-citationInsulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis
Dunaif, A. E. (1997) · Endocrine Reviews · doi:10.1210/er.18.6.774 · Cited by 1,167
Farooqi, I. S., Matarese, G., Lord, G. M., Keogh, J. M., Lawrence, E., Agwu, C., Sanna, V., Jebb, S. A., Perna, F., Fontana, S., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215693 · Cited by 1,105
Self-citationThe Syndromes of Insulin Resistance and Acanthosis Nigricans
Kahn, C. R., Flier, J. S., Bar, R. S., Archer, J. A., Görden, P., Martin, M. M., & Roth, J. (1976) · New England Journal of Medicine · doi:10.1056/nejm197604012941401 · Cited by 1,101
Role for Stearoyl-CoA Desaturase-1 in Leptin-Mediated Weight Loss
Cohen, P., Miyazaki, M., Socci, N. D., Hagge-Greenberg, A., Liedtke, W., Soukas, A. A., Sharma, R., Hudgins, L. C., Ntambi, J. M., & Friedman, J. M. (2002) · Science · doi:10.1126/science.1071527 · Cited by 826
Early onset of reproductive function in normal female mice treated with leptin
Chehab, F. F., Mounzih, K., Lu, R., & Lim, M. E. (1997) · Science · doi:10.1126/science.275.5296.88 · Cited by 822
Leptin accelerates the onset of puberty in normal female mice.
Ahima, R. S., Dushay, J. R., Flier, S. N., Prabakaran, D., & Flier, J. S. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119172 · Cited by 760
Flagged first, then by citations
Cited by
Sorted by citations
Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism
Park, H. K., & Ahima, R. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.08.004 · Cited by 710
Narrative Review: The Role of Leptin in Human Physiology: Emerging Clinical Applications
Kelesidis, T., Kelesidis, I., Chou, S. H.-H., & Mantzoros, C. S. (2010) · Annals of Internal Medicine · doi:10.7326/0003-4819-152-2-201001190-00008 · Cited by 693
Leptin in Human Physiology and Pathophysiology
Mantzoros, C. S., Magkos, F., Brinkoetter, M., Sienkiewicz, E., Dardeno, T. A., Kim, S.-Y., Hamnvik, O.-P. R., & Koniaris, A. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00315.2011 · Cited by 593
Puberty : ontogeny, neuroendocrinology, physiology, and disorders
Styne, D. M., Grumbach, M. M., Dennis, M., Styne, J., & Melvin, M. N. (1998) · Time to knit · doi:10.1016/b978-1-4160-2911-3.50026-1 · Cited by 546
The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society Practice Guideline
Brown, R. J., Araújo‐Vilar, D., Cheung, P. T., Dunger, D. B., Garg, A., Jack, M., Mungai, L., Oral, E. A., Patni, N., Rother, K. I., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-2466 · Cited by 536
Metadata
- Authors
- Musso, C., Cochran, E., Javor, E., Young, J., DePaoli, A. M., & Gorden, P.
- Affiliations
- National Institutes of Health (US)
- Amgen (United States) (US)
- Corresponding author
- Musso, Carla
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 54
- Issue
- 2
- Pages
- 255-263
- ISSN
- 0026-0495 (ISSN-L)
- OpenAlex
- W2059105920
- Semantic Scholar
- 9facc3ba9dec2ca44742978285cee6875b5d0fc5
- Cited by
- 146
- References
- 32
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 3 · 2020: 7 · 2019: 6 · 2018: 8 · 2017: 5 · 2016: 6 · 2015: 7 · 2014: 11 · 2013: 4 · 2012: 8
- FWCI
- 10.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- lipodystrophy, hypoleptinemia, hyperandrogenism, polycystic ovary syndrome, amenorrhea, menstrual function, luteinizing hormone, sex hormone-binding globulin, testosterone, insulin resistance, insulin-like growth factor, pituitary function, glycemic control, hypoglycemia, puberty
- MeSH terms
- Adolescent, Adult, Aged, Amenorrhea, Androgens, Blood Glucose, Child, Female, Humans, Insulin-Like Growth Factor I, Luteinizing Hormone, Lipodystrophy, Male, Menstruation, Pituitary Function Tests, Pituitary Gland, Polycystic Ovary Syndrome, Puberty, Recombinant Proteins, Sex Hormone-Binding Globulin, Testosterone, Thyroid Gland, Hyperandrogenism, Human Growth Hormone, Leptin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
