Evidence-Based Hormone Therapies

Alpha-MSH

Healthy men: the increase of serum LH with single/acute IV alpha-MSH treatment (1 trial, 7 men)

1. Limone P, Calvelli P, Altare F, Ajmone-Catt P, Lima T, Molinatti GM. Evidence for an interaction between alpha-MSH and opioids in the regulation of gonadotropin secretion in man. J Endocrinol Invest. 1997 Apr;20(4):207-10.

Melanotan I: 3 trials, 310 patients

Photosensitivity, insufficiently skin tanning: the increase in skin tanning and sun protection with subcutaneous implants or injections of melanotan 1 (3 trials, 310 patients)

2. Langendonk JG1, Balwani M, Anderson KE, Bonkovsky HL, Anstey AV, Bissell DM, Bloomer J, Edwards C, Neumann NJ, Parker C, Phillips JD, Lim HW, Hamzavi I, Deybach JC, Kauppinen R, Rhodes LE, Frank J, Murphy GM, Karstens FP, Sijbrands EJ, de Rooij FW, Lebwohl M, Naik H, Goding CR, Wilson JH, Desnick RJ. Afamelanotide for Erythropoietic Protoporphyria. N Engl J Med. 2015 Jul 2;373(1):48-59.
3. Barnetson RS, Ooi TK, Zhuang L, Halliday GM, Reid CM, Walker PC, Humphrey SM, Kleinig MJ. [Nle4-D-Phe7]-alpha-melanocyte-stimulating hormone significantly increased pigmentation and decreased UV damage in fair-skinned Caucasian volunteers. J Invest Dermatol. 2006 Aug;126(8):1869-78.
4. Fitzgerald LM, Fryer JL, Dwyer T, Humphrey SM. Effect of MELANOTAN, [Nle(4), D-Phe(7)]-alpha-MSH, on melanin synthesis in humans with MC1R variant alleles. Peptides. 2006 Feb;27(2):388-94.

Melanotan II : 3 trials, 30 participants

Healthy men: the skin tanning and increase in erectile function with melanotan II treatment (1 trial, 3 volunteers)

5. Dorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ, Hadley ME. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 1996;58(20):1777-84.

Male sexual dysfunction: the improvement with subcutaneous injections of melanotan II treatment (2 trials, 30 patients)

6. Wessells H, Levine N, Hadley ME, Dorr R, Hruby V. Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II. Int J Impot Res. 2000 Oct;12 Suppl 4:S74-9.
7. Wessells H, Gralnek D, Dorr R, Hruby VJ, Hadley ME, Levine N. Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Urology. 2000 Oct 1;56(4):641-6.

Bremelanotide: 4 trials, 767 patients 

Female sexual dysfunction: the improvement with intranasal bremelanotide treatment (3 trials, 425 patients)

8. Clayton AH, Althof SE, Kingsberg S, DeRogatis LR, Kroll R, Goldstein I, Kaminetsky J, Spana C, Lucas J, Jordan R, Portman DJ. Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial. Womens Health (Lond). 2016 Jun;12(3):325-37.
9. Safarinejad MR. Evaluation of the safety and efficacy of bremelanotide, a melanocortin receptor agonist, in female subjects with arousal disorder: a double-blind placebo-controlled, fixed-dose, randomized study. J Sex Med. 2008 Apr;5(4):887-97.
10. Diamond LE, Earle DC, Heiman JR, Rosen RC, Perelman MA, Harning R. An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist. J Sex Med.2006 Jul;3(4):628-38.

Male sexual dysfunction: the improvement with intranasal bremelanotide treatment (1 trial, 342 patients)

11. Safarinejad MR, Hosseini SY. Salvage of sildenafil failures with bremelanotide: a randomized, double-blind, placebo-controlled study. J Urol. 2008 Mar;179(3):1066-71.

MSH/ACTH(4-9): behaviorally the most potent ACTH-derived peptide but which is devoid of endocrine activity) (6 trials > 300 patients)

Healthy adults: the increase in wakefulness and reduction in sleep with MSH/ACTH (4-9) (1 trial, ?)

12. Steiger A, Guldner J, Knisatschek H, Rothe B, Lauer C, Holsboer F. Effects of an ACTH/MSH(4-9) analog (HOE 427) on the sleep EEG and nocturnal hormonal secretion in humans. Peptides. 1991 Sep-Oct;12(5):1007-10

Anxiety disorder: the slight reduction in anxiety in panic attack disorders only in with MSH/ACTH (4-9) (1 trial, ?)

13. Den Boer JA, Westenberg HG, De Vries H. The MSH/ACTH analog ORG 2766 in anxiety disorders. 1992 Jan-Feb;13(1):109-12.

Cancer (ovarian) during cisplatin chemotherapy: the reduction of cisplatin neuropathy with ACTH (4-9) analog treatment (1 trial, ?)

14. Gispen WH, Hamers FP, Vecht CJ, Jennekens FG, Neyt JP. ACTH/MSH like peptides in the treatment of cisplatin neuropathy. J Steroid Biochem Mol Biol. 1992 Sep;43(1-3):179-83.
15. van der Hoop RG, Vecht CJ, van der Burg ME, Elderson A, Boogerd W, Heimans JJ, Vries EP, van Houwelingen JC, Jennekens FG, Gispen WH, et al. Prevention of cisplatin neurotoxicity with an ACTH(4-9) analogue in patients with ovarian cancer. N Engl J Med. 1990 Jan 11;322(2):89-94

Cancer (ovarian) during cisplatin chemotherapy: no reduction of cisplatin neuropathy with ACTH (4-9) analog treatment, possibly some adverse effects (1 trial, 196 patients)

16. Roberts JA, Jenison EL, Kim K, Clarke-Pearson D, Langleben A. A randomized,multicenter, double-blind, placebo-controlled, dose-finding study of ORG 2766 in the prevention or delay of cisplatin-induced neuropathies in women with ovarian Gynecol Oncol. 1997 Nov;67(2):172-7

Cancer (testicular): during cisplatin chemotherapy: the reduction of cisplatin neuropathy with ACTH (4-9) analog treatment (1 trial, 42 patients)

17. van Gerven JM, Hovestadt A, Moll JW, Rodenburg CJ, Splinter TA, van Oosterom AT, Keizer L, Drogendijk TE, Groenhout CM, Vecht CJ, et al. The effects of an ACTH (4-9) analogue on development of cisplatin neuropathy in testicular cancer: a randomized trial. J Neurol. 1994 Jun;241(7):432

MSH/ACTH(4-10): 6 trials, 227 participants

Healthy adults: the increase in fat breakdown with single/acute intranasal MSH/ACTH (4-10) treatment (1 trial, 10 volunteers)

18. Wellhöner P, Hörster R, Jacobs F, Sayk F, Lehnert H, Dodt C. Intranasal application of the meanocortin 4 receptor agonist MSH/ACTH(4-10) in humans causes lipolysis in white adipose tissue. Int J Obes (Lond). 2012 May;36(5):703-8.

Healthy, normal-weight adults: the body fat reduction with 6 weeks of MSH/ACTH (4-10) treatment (1 trial, 36 volunteers)

19. Fehm HL, Smolnik R, Kern W, McGregor GP, Bickel U, Born J. The melanocortin melanocyte-stimulating hormone/adrenocorticotropin(4-10) decreases body fat in humans. J Clin Endocrinol Metab. 2001 Mar;86(3):1144-8.

Healthy adults: the increase in tendon reflexes and heart rate with acute MSH/ACTH (4-10) treatment (1 publication, 2 trials, 47volunteers)

20. Brunia CH, van Boxtel A. MSH/ACTH4-10 and task-induced increase in tendon reflexes and heart rate. Pharmacol Biochem Behav. 1978 Nov;9(5):615-8

Healthy adults: no significant effect on memory with acute MSH/ACTH (4-10) treatment (1 trial, 20 men)

21. Miller LH, Fischer SC, Groves GA, Rudrauff ME. MSH/ACTH4-10 influences on the CAR in human subjects: a negative finding. Pharmacol Biochem Behav. 1977 Nov;7(5):417-9

Healthy adults: the memory disturbance with single/acute intranasal MSH/ACTH (4-10) treatment (2 trials, 114 volunteers)

22. Smolnik R, Perras B, Molle M, Fehm HL, Born J. Event-related brain potentials and working memory function in healthy humans after single-dose and prolonged intranasal administration of adrenocorticotropin 4-10 and desacetyl-alpha-melanocyte stimulating hormone. J Clin Psychopharmacol. 2000 Aug;20(4):445-54.
23. Smolnik R, Mölle M, Fehm HL, Born J. Brain potentials and attention after acute and subchronic intranasal administration ofACTH 4-10 and desacetyl-alpha-MSH in humans. Neuroendocrinology. 1999 Jul;70(1):63-72.

MC4-NN2-0453 : 2 trials (136 patients)

Is a novel, long-acting, selective, melanocortin-4-receptor analog

Overweight to obese but otherwise healthy men: no effect on weight after 1 month of a melanocortin-4-receptor analog (1 publication, 2 trials, 136 patients)

24. Royalty JE, Konradsen G, Eskerod O, Wulff BS, Hansen BS. Investigation of safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of a long-acting α-MSH analog in healthy overweight and obese subjects. J Clin Pharmacol. 2014 Apr;54(4):394-404.

Low quality of life and fatigue: the improvement with MSH analog treatment (2 references)

1. Langendonk JG, Balwani M, Anderson KE, Bonkovsky HL, Anstey AV, Bissell DM, Bloomer J, Edwards C, Neumann NJ, Parker C, Phillips JD, Lim HW, Hamzavi I, Deybach JC, Kauppinen R, Rhodes LE, Frank J, Murphy GM, Karstens FPJ, Sijbrands EJG, de Rooij FWM, Lebwohl M, Naik H, Goding CR, Wilson JHP, Desnick RJ. Afamelanotide for erythropoietic protoporphyria. N Engl J Med. 2015 Jul 2;373(1):48-59.
2. Biolcati G, Marchesini E, Sorge F, Barbieri L, Schneider-Yin X, Minder EI. Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria. Br J Dermatol. 2015 Jun;172(6):1601-12.

Wakefulness: the improvement with MSH analog treatment (1 reference)

1. Steiger A, Guldner J, Knisatschek H, Rothe B, Lauer C, Holsboer F. Effects of an ACTH/MSH(4-9) analog (HOE 427) on the sleep EEG and nocturnal hormonal secretion in humans. Peptides. 1991 Sep-Oct;12(5):1007-10

Depression: the association with lower MSH levels (3 references) 

1. Maes M, DeJonckheere C, Vandervorst C, Schotte C, Cosyns P, Raus J, Suy E. Abnormal pituitary function during melancholia: reduced alpha-melanocyte-stimulating hormone secretion and increased intact ACTH non-suppression. J Affect Disord. 1991 Jul;22(3):149-57
2. Sonino N, Fava GA, Morphy MA, Pedersen RC. Effects of metyrapone and dexamethasone on pro-gamma-MSH and ACTH levels in depressed patients. Eur Neuropsychopharmacol. 1990 Nov;1(1):63-5
3. Morphy MA, Fava GA, Pedersen RC, Zielezny M, Sonino N, Brownie AC. Effects of metyrapone and dexamethasone upon pro-gamma-MSH plasma levels in depressed patients and healthy controls. J Affect Disord. 1990 Jul;19(3):183-9

Anxiety: the association with lower MSH precursor levels (1 reference) 

1. Asakawa A, Toyoshima M, Inoue K, Koizumi A. Ins2Akita mice exhibit hyperphagia and anxiety behavior via the melanocortin system. Int J Mol Med. 2007 Apr;19(4):649-52

Anxiety: the improvement with MSH and MSH analog treatments (humans) or worsening (rats) (5 references)

1. Den Boer JA, Westenberg HG, De Vries H. The MSH/ACTH analog ORG 2766 in anxiety disorders. 1992 Jan-Feb;13(1):109-12
2. Sandman CA, George JM, Nolan JD, van Riezen H, Kastin AJ. Enhancement of attention in man with ACTH/MSH 4-10. Physiol Behav. 1975 Oct;15(5):427-31
3. Kokare DM, Chopde CT, Subhedar NK. Participation of alpha-melanocyte stimulating hormone in ethanol-induced anxiolysis and withdrawal anxiety in rats. Neuropharmacology. 2006 Sep;51(3):536-45
4. Kokare DM, Dandekar MP, Chopde CT, Subhedar N. Interaction between neuropeptide Y and alpha-melanocyte stimulating hormone in amygdala regulates anxiety in rats. Brain Res. 2005 May 10;1043(1-2):107-14
5. Rao TL, Kokare DM, Sarkar S, Khisti RT, Chopde CT, Subhedar N. GABAergic agents prevent alpha-melanocyte stimulating hormone induced anxiety and anorexia in rats. Pharmacol Biochem Behav. 2003 Dec;76(3-4):417-23

Memory loss: the improvement with MSH and MSH analog treatments (better visual memory and attention) (8 references)

1. Gonzalez PV, Schiöth HB, Lasaga M, Scimonelli TN. Memory impairment induced by IL-1beta is reversed by alpha-MSH through central melanocortin-4 receptors. Brain Behav Immun. 2009 Aug;23(6):817-22
2. McBride RB, Beckwith BE, Swenson RR, Sawyer TK, Hadley ME, Matsunaga TO, Hruby VJ. The actions of melanin-concentrating hormone (MCH) on passive avoidance in rats: a preliminary study. Peptides. 1994;15(4):757-9
3. Pitsikas N, Spruijt BM, Algeri S, Gispen WH. The ACTH/MSH (4-9) analog Org2766 improves retrieval of information after a fimbria fornix transection. Peptides. 1990 Sep-Oct;11(5):911-4.
4. Yehuda S. Effects of alpha-MSH, TRH and AVP on learning and memory, pain threshold, and motor activity: preliminary results. Int J Neurosci. 1987 Feb;32(3-4):703-9
5. Handelmann GE, O’Donohue TL, Forrester D, Cook W. Alpha-melanocyte stimulating hormone facilitates learning of visual but not auditory discriminations. Peptides. 1983 Mar-Apr;4(2):145-8

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In men : (7 references)

1. Safarinejad MR, Hosseini SY. Salvage of sildenafil failures with bremelanotide: a randomized, double-blind, placebo-controlled study. J Urol. 2008 Mar;179(3):1066-71
2. Giuliano F, Clément P, Droupy S, Alexandre L, Bernabé J. Melanotan-II: Investigation of the inducer and facilitator effects on penile erection in anaesthetized rat. Neuroscience. 2006;138(1):293-301
3. Rosen RC, Diamond LE, Earle DC, Shadiack AM, Molinoff PB. Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra. Int J Impot Res. 2004 Apr;16(2):135-42
4. Ter Laak MP, Brakkee JH, Adan RA, Hamers FP, Gispen WH. The potent melanocortin receptor agonist melanotan-II promotes peripheral nerve regeneration and has neuroprotective properties in the rat. Eur J Pharmacol. 2003 Feb 21;462(1-3):179-83
5. Wessells H, Levine N, Hadley ME, Dorr R, Hruby V. Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II. Int J Impot Res. 2000 Oct;12 Suppl 4:S74-9

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Low skin pigmentation: the association with lower MSH levels (3 references)

1. Abe K, Nicholson WE, Liddle GW, Island DP, Orth DN. Radioimmunoassay of beta-MSH in human plasma and tissues. J Clin Invest. 1967 Oct;46(10):1609-16.
2. Bartelt RN, Altmeyer P, Stöhr L, Gornik P, HOlzmann H. Endocrinologic reactions following exposure to fluorescent lamps. Z Hautkr. 1986 Feb 1;61(3):105-10.
3. Schiller M, Brzoska T, Böhm M, Metze D, Scholzen TE, Rougier A,Luger TA. Solar-Simulated Ultraviolet Radiation-Induced Upregulation of the Melanocortin-1 Receptor, Proopiomelanocortin, and Melanocyte-Stimulating Hormone in Human Epidermis In Vivo. J Invest Derm. 2004;122, 468–476

Low skin pigmentation: the improvement with MSH analog treatment (5 references)

1. Langendonk JG1, Balwani M, Anderson KE, Bonkovsky HL, Anstey AV, Bissell DM, Bloomer J, Edwards C, Neumann NJ, Parker C, Phillips JD, Lim HW, Hamzavi I, Deybach JC, Kauppinen R, Rhodes LE, Frank J, Murphy GM, Karstens FP, Sijbrands EJ, de Rooij FW, Lebwohl M, Naik H, Goding CR, Wilson JH, Desnick RJ. Afamelanotide for Erythropoietic Protoporphyria. N Engl J Med. 2015 Jul 2;373(1):48-59
2. Ugwu SO, Blanchard J, Dorr RT, Levine N, Brooks C, Hadley ME, Aickin M, Hruby VJ. Skin pigmentation and pharmacokinetics of melanotan-I in humans. Biopharm Drug Dispos. 1997 Apr;18(3):259-69
3. Barnetson RS, Ooi TK, Zhuang L, Halliday GM, Reid CM, Walker PC, Humphrey SM, Kleinig MJ. [Nle4-D-Phe7]-alpha-melanocyte-stimulating hormone significantly increased pigmentation and decreased UV damage in fair-skinned Caucasian volunteers. J Invest Dermatol. 2006 Aug;126(8):1869-78
4. Dorr RT, Ertl G, Levine N, Brooks C, Bangert JL, Powell MB, Humphrey S, Alberts DS. Effects of a superpotent melanotropic peptide in combination with solar UV radiation on tanning of the skin in human volunteers. Arch Dermatol. 2004 Jul;140(7):827-35
5. Fitzgerald LM, Fryer JL, Dwyer T, Humphrey SM. Effect of MELANOTAN, [Nle(4), D-Phe(7)]-alpha-MSH, on melanin synthesis in humans with MC1R variant alleles. Peptides. 2006 Feb;27(2):388-94

Light hair pigmentation: the association with low MSH levels (light hair) or low (gray, white) or abnormal MSH receptor levels (red hair) (2 references)

1. Bartelt RN, Altmeyer P, Stöhr L, Holzmann H. Endocrinological reactions following UV A whole body irradiation] Derm Beruf Umwelt. 1985;33(2):50-5
2. Nanninga PB, Ghanem GE, Lejeune FJ, Bos JD, Westerhof W. Evidence for alpha-MSH binding sites on human scalp hair follicles: preliminary results. Pigment Cell Res. 1991 Oct;4(4):193-8

Nerve injury: regeneration with MSH and MSH analog treatments (5 references)

1. Ter Laak MP, Brakkee JH, Adan RA, Hamers FP, Gispen WH. The potent melanocortin receptor agonist melanotan-II promotes peripheral nerve regeneration and has neuroprotective properties in the rat. Eur J Pharmacol. 2003 Feb 21;462(1-3):179-83
2. Ter Laak MP, Brakkee JH, Adan RA, Hamers FP, Gispen WH. The potent melanocortin receptor agonist melanotan-II promotes peripheral nerve regeneration and has neuroprotective properties in the rat. Eur J Pharmacol. 2003 Feb 21;462(1-3):179-83
3. Joosten EA, Majewska B, Houweling DA, Bär PR, Gispen WH. Alpha-melanocyte stimulating hormone promotes regrowth of injured axons in the adult rat spinal cord. J Neurotrauma. 1999 Jun;16(6):543-53.
4. Lankhorst AJ, Duis SE, ter Laak MP, Joosten EA, Hamers FP, Gispen WH. Functional recovery after central infusion of alpha-melanocyte-stimulating hormone in rats with spinal cord contusion injury. J Neurotrauma. 1999 Apr;16(4):323-31
5. van de Meent H, Hamers FP, Lankhorst AJ, Joosten EA, Gispen WH. Beneficial effects of the melanocortin alpha-melanocyte-stimulating hormone on clinical and neurophysiological recovery after experimental spinal cord injury. Neurosurgery. 1997 Jan;40(1):122-30

Arterial hypertension: the association with lower MSH levels (1 reference)

1. Ni XP, Humphreys MH. Prevention of salt-induced hypertension by an analog of gamma-melanocyte-stimulating hormone in the rat. Am J Hypertens. 2007 Aug;20(8):862-5

Arterial hypertension: the improvement with MSH treatment (2 references)

1. Tai MH, Weng WT, Lo WC, Chan JY, Lin CJ, Lam HC, Tseng CJ. Role of nitric oxide in alpha-melanocyte-stimulating hormone-induced hypotension in the nucleus tractus solitarii of the spontaneously hypertensive rats. J Pharmacol Exp Ther. 2007 May;321(2):455-61
2. Ni XP, Humphreys MH. Prevention of salt-induced hypertension by an analog of gamma-melanocyte-stimulating hormone in the rat. Am J Hypertens. 2007 Aug;20(8):862-5

Cardiac function: the improvement with MSH treatment in rats (1 reference)

1. Szokol M, Priksz D, Bombicz M, Varga B, Kovacs A, Fulop GA, Csipo T, Posa A, Toth A, Papp Z, Szilvassy Z, Juhasz B. Long term osmotic mini-pump treatment with alpha-MSH improves myocardial function in Zucker Diabetic Fatty rats. Molecules. 2017 Oct 12;22(10).

Excess appetite: the association with low MSH levels (1 reference)

1. MacNeil DJ, Howard AD, Guan X, Fong TM, Nargund RP, Bednarek MA, Goulet MT, Weinberg DH, Strack AM, Marsh DJ, Chen HY, Shen CP, Chen AS, Rosenblum CI, MacNeil T, Tota M, MacIntyre ED, Van der Ploeg LH.. The role of melanocortins in body weight regulation: opportunities for the treatment of obesity. Eur J Pharmacol 2002 Apr 12;440(2-3):141-57

Excessive appetite: the reduction with MSH and MSH analog treatments (6 references)

1. Wang J, Ling S, Usami T, Murata T, Narita K, Higuchi T. Effects of ghrelin, corticotrophin-releasing hormone, and melanotan-II on food intake in rats with paraventricular nucleus lesions. Exp Clin Endocrinol Diabetes. 2007 Nov;115(10):669-73
2. Glavas MM, Joachim SE, Draper SJ, Smith MS, Grove KL. Melanocortinergic activation by melanotan II inhibits feeding and increases uncoupling protein 1 messenger ribonucleic acid in the developing rat. Endocrinology. 2007 Jul;148(7):3279-87
3. Li G, Zhang Y, Wilsey JT, Scarpace PJ. Unabated anorexic and enhanced thermogenic responses to melanotan II in diet-induced obese rats despite reduced melanocortin 3 and 4 receptor expression. J Endocrinol. 2004 Jul;182(1):123-32
4. Hillebrand JJ, Kas MJ, Adan RA. a-MSH enhances activity-based anorexia. Peptides. 2005 Oct;26(10):1690-6
5. Hansen MJ, Ball MJ, Morris MJ. Enhanced inhibitory feeding response to alpha-melanocyte stimulating hormone in the diet-induced obese rat. Brain Res. 2001 Feb 16;892(1):130-7

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Obesity: the association with insufficient MSH levels (2 references)

1. Vehapoğlu A, Türkmen S, Terzioğlu Ş. Alpha-melanocyte-stimulating hormone and agouti-related protein: do they play a role in appetite regulation in childhood obesity? J Clin Res Pediatr Endocrinol. 2016 Mar 5;8(1):40-7.
2. Roth CL, Enriori PJ, Gebhardt U, Hinney A, Müller HL, Hebebrand J, Reinehr T, Cowley MA. Changes of peripheral alpha-melanocyte-stimulating hormone in childhood obesity. Metabolism. 2010 Feb;59(2):186-94.

Obesity: the association with abnormal MSH receptor levels or genes (3 references)

1. Dubern B, Clément K, Pelloux V, Froguel P, Girardet JP, Guy-Grand B, Tounian P. Mutational analysis of melanocortin-4 receptor, agouti-related protein, and alpha-melanocyte-stimulating hormone genes in severely obese children. J Pediatr. 2001 Aug;139(2):204-9
2. Biebermann H, Castañeda TR, van Landeghem F, von Deimling A, Escher F, Brabant G, Hebebrand J, Hinney A, Tschöp MH, Grüters A, Krude H. A role for beta-melanocyte-stimulating hormone in human body-weight regulation. Cell Metab. 2006 Feb;3(2):141-6.
3. Lee YS, Challis BG, Thompson DA, Yeo GS, Keogh JM, Madonna ME, Wraight V, Sims M, Vatin V, Meyre D, Shield J, Burren C, Ibrahim Z, Cheetham T, Swift P, Blackwood A, Hung CC, Wareham NJ, Froguel P, Millhauser GL, O’Rahilly S, Farooqi IS. A POMC variant implicates beta-melanocyte-stimulating hormone in the control of human energy balance. Cell Metab. 2006 Feb;3(2):135-40.

Obesity: the improvement with MSH and MSH analog treatments (6 references)

1. Wellhöner P, Hörster R, Jacobs F, Sayk F, Lehnert H, Dodt C. Intranasal application of the melanocortin 4 receptor agonist MSH/ACTH(4-10) in humans causes lipolysis in white adipose tissue. Int J Obes (Lond). 2012 May;36(5):703-8.
2. Royalty JE, Konradsen G, Eskerod O, Wulff BS, Hansen BS. Investigation of safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of a long-acting α-MSH analog in healthy overweight and obese subjects. J Clin Pharmacol. 2014 Apr;54(4):394-404.
3. Costa JL, Hochgeschwender U, Brennan M. The role of melanocyte-stimulating hormone in insulin resistance and type 2 diabetes mellitus. Treat Endocrinol. 2006;5(1):7-13.
4. Brennan MB, Costa JL, Forbes S, Reed P, Bui S, Hochgeschwender U. Alpha-melanocyte-stimulating hormone is a peripheral, integrative regulator of glucose and fat metabolism. Ann N Y Acad Sci. 2003 Jun;994:282-7.
5. Fehm HL, Smolnik R, Kern W, McGregor GP, Bickel U, Born J. The melanocortin melanocyte-stimulating hormone/adrenocorticotropin(4-10) decreases body fat in humans. J Clin Endocrinol Metab. 2001 Mar;86(3):1144-8.

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Atherosclerosis: the improvement with IGF-1 treatment (2 references)

1. Sukhanov S, Higashi Y, Shai SY, Vaughn C, Mohler J, Li Y, Song YH, Titterington J, Delafontaine P. IGF-1 reduces inflammatory responses, suppresses oxidative stress, and decreases atherosclerosis progression in ApoE-deficient mice. Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2684-9
2. Cittadini A, Monti MG, Castiello MC, D’Arco E, Galasso G, Sorriento D, Saldamarco L, De Paulis A, Napoli R, Iaccarino G, Saccà L. Insulin-like growth factor-1 protects from vascular stenosis and accelerates re-endothelialization in a rat model of carotid artery injury. J Thromb Haemost. 2009 Nov;7(11):1920-8.

Arterial hypertension: the association with lower IGF-1 levels (7 references)

1. Schutte AE, Schutte R, Smith W, Huisman HW, Mels CM, Malan L, Fourie CM, Malan NT, Van Rooyen JM, Kruger R, Conti E. Compromised bioavailable IGF-1 of black men relates favorably to ambulatory blood pressure: The SABPA study. Atherosclerosis. 2014 Mar;233(1):139-44.
2. Zhang L, Curhan GC, Forman JP. Plasma insulin-like growth factor-1 level and risk of incident hypertension in nondiabetic women. J Hypertens. 2011 Feb;29(2):229-35
3. Sesti G, Sciacqua A, Scozzafava A, Vatrano M, Angotti E, Ruberto C, Santillo E, Parlato G, Perticone F. Effects of growth hormone and insulin-like growth factor-1 on cardiac hypertrophy of hypertensive patients. J Hypertens. 2007 Feb;25(2):471-7
4. Lawlor DA, Ebrahim S, Smith GD, Cherry L, Watt P, Sattar N. The association of insulin-like-growth factor 1 (IGF-1) with incident coronary heart disease in women: findings from the prospective British Women’s Heart and Health Study. Atherosclerosis. 2008 Nov;201(1):198-204
5. Paolisso G, Tagliamonte MR, Rizzo MR, Rotondi M, Gualdiero P, Gambardella A, Barbieri M, Carella C, Giugliano D, Varricchio M. Mean arterial blood pressure and serum levels of the molar ratio of insulin-like growth factor-1 to its binding protein-3 in healthy centenarians.J Hypertens. 1999 Jan;17(1):67-73.

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Coronary heart disease: the association with lower IGF-1 levels (6 references)

1. Dizdarević-Hudić L, Kusljugić Z, Baraković F, Hajder M, Hudić I. Do growth hormone and insulin-like growth factor 1 affect prognosis in patients with killip I and II class acute myocardial infarction? Acta Clin Croat. 2016 Sep;55(3):345-353.
2. Hu WS, Hwang JM. Association of serum cytokines, human growth hormone, insulin-like growth factor (IGF)-I, IGF-II and IGF-binding protein (IGFBP)-3 with coronary artery disease. Chin J Physiol. 2012 Aug 31;55(4):267-73.
3. Conti E, Andreotti F, Sestito A, Riccardi P, Menini E, Crea F, Maseri A, Lanza GA. Reduced levels of insulin-like growth factor-1 in patients with angina pectoris, positive exercise stress test, and angiographically normal epicardial coronary arteries. Am J Cardiol. 2002 Apr 15;89(8):973-5.
4. Lawlor DA, Ebrahim S, Smith GD, Cherry L, Watt P, Sattar N. The association of insulin-like-growth factor 1 (IGF-1) with incident coronary heart disease in women: findings from the prospective British Women’s Heart and Health Study. Atherosclerosis. 2008 Nov;201(1):198-204
5. Sekuri C, Arslan O, Utük O, Bayturan O, Onur E, Tezcan UK, Tavli T. Serum level of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in acute coronary syndromes and relationship with prognosis. Anadolu Kardiyol Derg. 2004 Sep;4(3):209-12

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Coronary heart disease and other cardiac diseases: the improvement with IGF-1 treatment (5 references)

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5. Duerr RL, Huang S, Miraliakbar HR, Clark R, Chien KR, Ross J Jr. Insulin-like growth factor-1 enhances ventricular hypertrophy and function during the onset of experimental cardiac failure. J Clin Invest. 1995 Feb;95(2):619-27

Heart failure: the association with lower IGF-1 levels (6 references)

1. Barroso MC, Kramer F, Greene SJ, Scheyer D, Köhler T, Karoff M, Seyfarth M, Gheorghiade M, Dinh W. Serum insulin-like growth factor-1 and its binding protein-7: potential novel biomarkers for heart failure with preserved ejection fraction. BMC Cardiovasc Disord. 2016 Oct 21;16(1):199.
2. Peng J, Fu J, Deng SZ, Wang RG, Liu L, Sun DM, Xia K. Changes in serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3, and their significance in children with left-to-right shunt congenital heart disease associated with heart failure. Zhongguo Dang Dai Er Ke Za Zhi. 2013 Apr;15(4):277-80.
3. Watanabe S, Tamura T, Ono K, Horiuchi H, Kimura T, Kita T, Furukawa Y. Insulin-like growth factor axis (insulin-like growth factor-I/insulin-like growth factor-binding protein-3) as a prognostic predictor of heart failure: association with adiponectin. Eur J Heart Fail. 2010 Nov;12(11):1214-22.
4. Sesti G, Sciacqua A, Scozzafava A, Vatrano M, Angotti E, Ruberto C, Santillo E, Parlato G, Perticone F. Effects of growth hormone and insulin-like growth factor-1 on cardiac hypertrophy of hypertensive patients. J Hypertens. 2007 Feb;25(2):471-7
5. Osterziel KJ, Ranke MB, Strohm O, Dietz R. The somatotrophic system in patients with dilated cardiomyopathy: relation of insulin-like growth factor-1 and its alterations during growth hormone therapy to cardiac function. Clin Endocrinol (Oxf). 2000 Jul;53(1):61-8

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Cardiovascular disease and mortality: the increase with lower IGF-1 levels (2 references)

1. Laughlin GA, Barrett-Connor E, Criqui MH, Kritz-Silverstein D. The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-1 levels with all cause and cardiovascular disease mortality in older adults: the Rancho Bernardo Study. J Clin Endocrinol Metab. 2004 Jan;89(1):114-20
2. Juul A, Scheike T, Davidsen M, Gyllenborg J, Jorgensen T. Low serum insulin-like growth factor I is associated with increased risk of ischemic heart disease: a population-based case-control study. Circulation. 2002 Aug 20;106(8):939-44.

Obesity and high body mass index: the association with lower IGF-1 levels (29 references)

1. Izumi S, Ribeiro-Filho FF, Carneiro G, Togeiro SM, Tufik S, Zanella MT. IGF-1 levels are inversely associated with metabolic syndrome in obstructive sleep apnea. J Clin Sleep Med. 2016 Apr 15;12(4):487-93.
2. Katz LE, Gralewski KA, Abrams P, Brar PC, Gallagher PR, Lipman TH, Brooks LJ, Koren D. Insulin-like growth factor-I and insulin-like growth factor binding protein-1 are related to cardiovascular disease biomarkers in obese adolescents. Pediatr Diabetes. 2016 Mar;17(2):77-86.
3. Bjersing JL, Erlandsson M, Bokarewa MI, Mannerkorpi K. Exercise and obesity in fibromyalgia: beneficial roles of IGF-1 and resistin? Arthritis Res Ther. 2013 Feb 27;15(1):R34.
4. Galli G, Pinchera A, Piaggi P, Fierabracci P, Giannetti M, Querci G, Scartabelli G, Manetti L, Ceccarini G, Martinelli S, Di Salvo C, Anselmino M, Bogazzi F, Landi A, Vitti P, Maffei M, Santini F. Serum insulin-like growth factor-1 concentrations are reduced in severely obese women and raise after weight loss induced by laparoscopic adjustable gastric banding. Obes Surg. 2012 Aug;22(8):1276-80.
5. Savastano S, Di Somma C, Pizza G, De Rosa A, Nedi V, Rossi A, Orio F, Lombardi G, Colao A, Tarantino G. Liver-spleen axis, insulin-like growth factor-(IGF)-I axis and fat mass in overweight/obese females. J Transl Med. 2011 Aug 16;9:136.

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Obesity: the improvement with IGF-1 treatment (3 references)

1. Thompson JL, Butterfield GE, Gylfadottir UK, Yesavage J, Marcus R, Hintz RL, Pearman A, Hoffman AR. Effects of human growth hormone, insulin-like growth factor I, and diet and exercise on body composition of obese postmenopausal women. : J Clin Endocrinol Metab. 1998 May;83(5):1477-84
2. Laron Z, Anin S, Klipper-Aurbach Y, Klinger B. Effects of insulin-like growth factor on linear growth, head circumference, and body fat in patients with Laron-type dwarfism. Lancet. 1992 May 23;339(8804):1258-61
3. Hayes VY, Urban RJ, Jiang J, Marcell TJ, Helgeson K, Mauras N. Recombinant human growth hormone and recombinant human insulin-like growth factor I diminish the catabolic effects of hypogonadism in man: metabolic and molecular effects. J Clin Endocrinol Metab. 2001 May;86(5):2211-9

Metabolic syndrome: the association with lower IGF-1 levels (6 references)

1. Liang S, Hu Y, Liu C, Qi J, Li G. Low insulin-like growth factor 1 is associated with low high-density lipoprotein cholesterol and metabolic syndrome in Chinese nondiabetic obese children and adolescents: a cross-sectional study. Lipids Health Dis. 2016 Jun 24;15:112.
2. Koegelenberg AS, Schutte R, Smith W, Schutte AE. Bioavailable IGF-1 and its relation to the metabolic syndrome in a bi-ethnic population of men and women. Horm Metab Res. 2016 Feb;48(2):130-6.
3. Mallea-Gil MS, Ballarino MC, Spiraquis A, Iriarte M, Kura M, Gimenez S, Oneto A, Guitelman M, Machado R, Miguel CM. IGF-1 levels in different stages of liver steatosis and its association with metabolic syndrome. Acta Gastroenterol Latinoam. 2012 Mar;42(1):20-6.
4. Oh J, Kim JY, Park S, Youn JC, Son NH, Shin DJ, Lee SH, Kang SM, Jee SH, Jang Y. The relationship between insulin-like growth factor-1 and metabolic syndrome, independent of adiponectin. Clin Chim Acta. 2012 Feb 18;413(3-4):506-10.
5. Parekh N, Roberts CB, Vadiveloo M, Puvananayagam T, Albu JB, Lu-Yao GL. Lifestyle, anthropometric, and obesity-related physiologic determinants of insulin-like growth factor-1 in the Third National Health and Nutrition Examination Survey (1988-1994). Ann Epidemiol. 2010 Mar;20(3):182-93.

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Type 1 diabetes: the association with low IGF-1 levels (12 references)

1. Hamed MS, El-Sherbeny AA, El-Din AMB. Prepubertal IGF-1 and possible relation with physical features of growth and Type 1 Diabetes Mellitus. Curr Diabetes Rev. 2019;15(5):420-428.
2. Song W, Qiao Y, Xue J, Zhao F, Yang X, Li G. The association of insulin-like growth factor-1 standard deviation score and height in Chinese children with type 1 diabetes mellitus. Growth Factors. 2018 Dec;36(5-6):274-282.
3. Żebrowska A, Hall B, Maszczyk A, Banaś R, Urban J. Brain-derived neurotrophic factor, insulin like growth factor-1 and inflammatory cytokine responses to continuous and intermittent exercise in patients with type 1 diabetes. Res Clin Pract. 2018 Oct;144:126-136.
4. Gutefeldt K, Hedman CA, Thyberg ISM, Bachrach-Lindström M, Spångeus A, Arnqvist HJ. Dysregulated growth hormone-insulin-like growth factor-1 axis in adult type 1 diabetes with long duration. Clin Endocrinol (Oxf). 2018 Jul 10.
5. Chisalita SI, Ludvigsson J. Insulin-Like Growth Factor-1 at Diagnosis and during Subsequent Years in Adolescents with Type 1 Diabetes. J Diabetes Res. 2018 Mar 20;2018:8623560.

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Type 1 diabetes: the improvement with IGF-1 treatment (1 reference)

1. Liu F, Yu M, Zhu Q. Recombinant human IGF-1 prevents type 1 diabetes in female non-obese diabetic mice. Zhonghua Yu Fang Yi Xue Za Zhi. 2000 Sep;34(5):281-3

Type 2 diabetes, insulin resistance: the association with lower IGF-1 levels (7 references)

1. Touskova V, Trachta P, Kavalkova P, Drapalova J, Haluzikova D, Mraz M, Lacinova Z, Marek J, Haluzik M. Serum concentrations and tissue expression of components of insulin-like growth factor-axis in females with type 2 diabetes mellitus and obesity: the influence of very-low-calorie diet. Mol Cell Endocrinol. 2012 Sep 25;361(1-2):172-8.
2. Kanazawa I, Yamaguchi T, Sugimoto T. Effects of intensive glycemic control on serum levels of insulin-like growth factor-I and dehydroepiandrosterone sulfate in Type 2 diabetes mellitus. J Endocrinol Invest. 2012 May;35(5):469-72.
3. Kanazawa I, Yamaguchi T, Sugimoto T. Serum insulin-like growth factor-I is negatively associated with serum adiponectin in type 2 diabetes mellitus. Growth Horm IGF Res. 2011 Oct;21(5):268-71.
4. Gannon MC, Nuttall FQ. Effect of a high-protein diet on ghrelin, growth hormone, and insulin-like growth factor-I and binding proteins 1 and 3 in subjects with type 2 diabetes mellitus. Metabolism. 2011 Sep;60(9):1300-11.
5. Sesti G, Sciacqua A, Scozzafava A, Vatrano M, Angotti E, Ruberto C, Santillo E, Parlato G, Perticone F. Effects of growth hormone and insulin-like growth factor-1 on cardiac hypertrophy of hypertensive patients. J Hypertens. 2007 Feb;25(2):471-7

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Type 2 diabetes: the improvement with IGF-1 treatment (4 references)

1. Guler HP, Zapf J, Froesch ER. Short-term metabolic effects of recombinant human insulin-like growth factor I in healthy adults. N Engl J Med. 1987 Jul 16;317(3):137-4
2. Bianda TL, Hussain MA, Keller A, Glatz Y, Schmitz O, Christiansen JS, Alberti KG, Froesch ER. Insulin-like growth factor-I in man enhances lipid mobilization and oxidation induced by a growth hormone pulse. Diabetologia. 1996 Aug;39(8):961-9
3. Kerr D, Tamborlane WV, Rife F, Sherwin RS. Effect of insulin-like growth factor-1 on the responses to and recognition of hypoglycemia in humans. A comparison with insulin. J Clin Invest. 1993 Jan;91(1):141-7
4. Vaccarello MA, Diamond FB Jr, Guevara-Aguirre J, Rosenbloom AL, Fielder PJ, Gargosky S, Cohen P, Wilson K, Rosenfeld RG. Hormonal and metabolic effects and pharmacokinetics of recombinant insulin-like growth factor-I in growth hormone receptor deficiency/Laron syndrome. J Clin Endocrinol Metab. 1993 Jul;77(1):273-80

Osteoarthritis: the association with lower IGF-1 levels (1 reference)

1. Lis K. Insulin-like growth factor 1 and growth hormone as the markers of osteoarthritis. Chir Narzadow Ruchu Ortop Pol. 2008 Jan-Feb;73(1):49-52

Osteoarthritis: the improvement with IGF-1 treatment (2 references)

1. Rogachefsky RA, Dean DD, Howell DS, Altman RD. Treatment of canine osteoarthritis with insulin-like growth factor-1 (IGF-1) and sodium pentosan polysulfate. Osteoarthritis Cartilage. 1993 Apr;1(2):105-14
2. Davies LC, Blain EJ, Gilbert SJ, Caterson B, Duance VC. The potential of IGF-1 and TGFbeta1 for promoting “adult” articular cartilage repair: an in vitro study. Tissue Eng Part A. 2008 Jul;14(7):1251-61

Rheumatoid arthritis: the association with lower IGF-1 levels (2 references)

1. Neidel J. Changes in systemic levels of insulin-like growth factors and their binding proteins in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2001 Jan-Feb;19(1):81-4
2. Melikoglu MA, Karatay S, Senel K, Akcay F. Association between dynamic exercise therapy and IGF-1 and IGFBP-3 concentrations in the patients with rheumatoid arthritis. Rheumatol Int. 2006 Feb;26(4):309-13

Fibromyalgia: the association with lower IGF-1 levels (3 references)

1. Neidel J. Changes in systemic levels of insulin-like growth factors and their binding proteins in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2001 Jan-Feb;19(1):81-4
2. Leal-Cerro A, Povedano J, Astorga R, Gonzalez M, Silva H, Garcia-Pesquera F, Casanueva FF, Dieguez C. The growth hormone (GH)-releasing hormone-GH-insulin-like growth factor-1 axis in patients with fibromyalgia syndrome. J Clin Endocrinol Metab. 1999 Sep;84(9):3378-81
3. Samborski W, Stratz T, Schochat T, Mennet P, Müller W. Biochemical changes in fibromyalgia. Z Rheumatol. 1996 May-Jun;55(3):168-73