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.
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Female patients generally had hypogonadotropic amenorrhea.
“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]
Most female patients resumed and sustained normal menses following initiation of r-metHuLeptin.
“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]
The resumption of normal menses in female patients was consistent with normalization of their gonadotropin axis.
“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]
R-metHuLeptin therapy led to a decrease in serum androgen levels and normal cyclic menses in women of reproductive age.
“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]
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.
“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]
Treatment with metreleptin has improved reproductive function in other leptin-deficient conditions, including congenital leptin deficiency and lipodystrophy, in uncontrolled pilot studies.
“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]
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- 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
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