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
Items 101–145 of 145
Yamamoto, A., Kusakabe, T., Satô, K., Tokizaki, T., Sakurai, K., & Abe, S. (2019) · Acta Radiologica Open · doi:10.1177/2058460119892407 · Cited by 6
Iwanishi, M., Kusakabe, T., Azuma, C., Tezuka, Y., Yamamoto, Y., Ito‐Kobayashi, J., Washiyama, M., Morimoto, M., & Ebihara, K. (2019) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2019.04.034 · Cited by 6
Jones, A. G., & Hattersley, A. T. (2010) · Wiley eBooks · doi:10.1002/9781444324808.ch15 · Cited by 6
Ahima, R. S., Scolaro, L. M., & Park, H.-K. (2016) · Springer eBooks · doi:10.1007/978-3-319-11251-0_24 · Cited by 5
Meikle, A. W. (2006) · Yearbook of Endocrinology · doi:10.1016/s0084-3741(08)70439-6 · Cited by 5
Leptin restores markers of female fertility in lipodystrophy
Eifler, L. K., Hoffmann, A., Wagner, I. V., Klöting, N., Sahlin, L., Ebert, T., Jeßnitzer, B., Lössner, U., Stümvoll, M., Söder, O., et al. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.07.015 · Cited by 4
Gao, C., & Mantzoros, C. S. (2010) · Elsevier eBooks · doi:10.1016/b978-1-4160-5583-9.00038-1 · Cited by 4
Brown, R. J., Akıncı, B., Al-Yaarubi, S., Bismuth, É., Cappa, M., Deeb, A., Kamrath, C., Musso, C., Patni, N., Prodam, F., et al. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1597053 · Cited by 4
Self-citationNeuroendocrine Regulation of Appetite and Body Weight
Wilkinson, M., & Imran, S. A. (2018) · Cambridge University Press eBooks · doi:10.1017/9781108149938.005 · Cited by 4
Miehle, K., von Schnurbein, J., Faßhauer, M., Stümvoll, M., Borck, G., & Wabitsch, M. (2017) · Medizinische Genetik · doi:10.1007/s11825-017-0162-2 · Cited by 3
Besci, Ö., Güler, M. Ç., Foss‐Freitas, M. C., & Oral, E. A. (2025) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2025.2574318 · Cited by 2
Lipodystrophy look-alikes: navigating diagnostic overlap with endocrine diseases
Ceccarini, G., Gilio, D., Magno, S., Palladino, L., & Santini, F. (2026) · European Journal of Endocrinology · doi:10.1093/ejendo/lvag067 · Cited by 2
Jackson, M. B., & Ahima, R. S. (2007) · Humana Press eBooks · doi:10.1007/978-1-59745-370-7_3 · Cited by 2
Metabolic Disorders in HIV-infected Children Metabolic Disorders in HIVinfected Children
Liguoro, S. M. (2014) · Journal of Metabolic Syndrome · doi:10.4172/2167-0943.1000169 · Cited by 2
Ahima, R. S., Scolaro, L. M., & Park, H.-K. (2015) · Springer eBooks · doi:10.1007/978-3-319-12125-3_24-1 · Cited by 2
Androgens and Severe Insulin Resistance States: Basic and Clinical Aspects
Gambineri, A., Zanotti, L., & Gasparini, D. I. (2019) · Frontiers of hormone research · doi:10.1159/000494911 · Cited by 2
The emerging clinical significance of leptin in humans with absolute or relative leptin deficiency
Moschos, S. J., & Mantzoros, C. S. (2005) · Current Opinion in Internal Medicine · doi:10.1097/01.med.0000177421.80858.74 · Cited by 2
Misra, S., & Hattersley, A. T. (2016) · Wiley eBooks · doi:10.1002/9781118924853.ch18 · Cited by 2
Викторовна, Ф. Н., Романовна, Р. Е., Koksharova, E., Фархадовна, Б. Ф., Vasiluev, P. A., Minniakhmetov, I. R., Eremina, I. A., & Shestakova, M. V. (2025) · Diabetes Mellitus · doi:10.14341/dm13333 · Cited by 1
Ahima, R. S., & Park, H. K. (2023) · Springer eBooks · doi:10.1007/978-3-031-40116-9_24 · Cited by 1
Substrate Metabolism in the Diabetic Heart
Onay-Beşi̇kçi̇, A. (2013) · Springer eBooks · doi:10.1007/978-1-4614-9317-4_4 · Cited by 1
Impact of Obesity on Female Reproductive Health
Olatinwo, M. O., Harp, D., Thompson, W. E., Park, H.-K., & Mathews, R. P. (2010) · Springer eBooks · doi:10.1007/978-1-4419-1607-5_17 · Cited by 1
Clinical Applications of Leptin
Oral, E. A., & DePaoli, A. M. (2006) · Springer eBooks · doi:10.1007/978-0-387-31416-7_17
Self-citationMapping the Neural Mechanisms by which Leptin Regulates Distinct Physiological Functions.
Louis, G. W. (2010) · Deep Blue (University of Michigan)
METRELEPTINA: TRATAMIENTO PARA LAS COMPLICACIONES METABÓLICAS DE LA LIPODISTROFIA GENERALIZADA.
Lima-Martínez, M. M. (2016) · Actualidad Contable FACES
Late-Breaking Clinical Trial Report
Chan, J. L., Lutz, K., Cochran, E. K., Huang, W., Peters, Y., Weyer, C., & Görden, P. (2011)
Self-citationDunnigan-Type Familial Partial Lipodystrophy: Understanding and Treating the Syndrome
Santos, A. R. J., Ferreira, S. P., Benazzi, M., Capra, M., Medeiros, H. P. A., de Jesus, A. L. C., de Almeida, M. H., de Sá, L. B. P. C., & Arbex, A. K. (2017) · Open Journal of Endocrine and Metabolic Diseases · doi:10.4236/ojemd.2017.71003
Regulation of the Timing of Puberty: Exploration of the Role of Epigenetics
Rzeczkowska, P. A. (2012) · TSpace (University of Toronto)
Lipodystrophie et lipoatrophie
Vatier, C., Mosbah, H., Zammouri, J., Donadille, B., Janmaat, S., Lascols, O., Fève, B., Jéru, I., & Vigouroux, C. (2021) · Elsevier eBooks · doi:10.1016/b978-2-294-76753-1.00061-8
Identification of hypothalamic sites that control puberty onset and sexual maturation
Greenwald-Yarnell, M. L. (2013) · Deep Blue (University of Michigan)
Ahima, R. S., Scolaro, L. M., & Park, H.-K. (2017) · Springer eBooks · doi:10.1007/978-3-319-12125-3_24-2
Simha, V., & Garg, A. (2020) · Contemporary cardiology · doi:10.1007/978-3-030-56514-5_22
3: The Lipodystrophy Syndromes: Clinical Features and Treatments
Mattingly, M., Valencia, A., Cochran, E. K., Brown, R. J., & Gorden, P. (2018) · American Diabetes Association eBooks · doi:10.2337/9781580406666.03
Self-citationAhima, R. S., & Park, H. K. (2023) · Springer eBooks · doi:10.1007/978-3-319-12125-3_24-3
Leptin-related disorders of the nervous system
Saez-Calveras, N., Ishii, M., Elmquist, J. K., & Williams, K. W. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-19041-4.00027-3
Somali, M., Korakas, E., Pizirtzidou, E., Efstathiadou, Z. A., Sapranidis, M., & Mouslech, Z. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1715799
Lima, J. G., Valério, C. M., Godoy‐Matos, A. F., Carvalho, G., Dantas, J. R., Salles, J. E. N., Gerchman, F., & Montenegro, R. M. (2025) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-025-01990-4 · Cited by 1
Al-Yaarubi, S., Alsagheir, A., Shidhani, A. N. A., Alzelaye, S., Alghazir, N., Brema, I. A., Alsaffar, H., Dubayee, M. A., Alshahrani, A., Abdelmeguid, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26692813
Manejo avanzado del síndrome de Donohue: control glucémico con bomba de infusión
Barrón-Balderas, A., Aguirre-Salas, L. M., Robledo-Aceves, M., Lona-Reyes, J. C., & Cabrera-Arias, S. M. (2025) · Salud Jalisco · doi:10.35366/121775
Weiskorn, J., & Kordonouri, O. (2026) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2026-0516
Lipodystrophy: The experiment of nature to study leptin
Ahima, R. S., & Jackson, M. B. (2006) · Springer eBooks · doi:10.1007/978-0-387-31416-7_12
Ahima, R. S., & Varela, G. M. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-374145-5.00332-6
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
