Evidence-Based Hormone Therapies

Healthy adults: pharmacokinetics of 48h IV of relaxin treatment (safe and tolerable and efficient) (1 trial, 32 participants)

1. Dahlke M, Ng D, Yamaguchi M, Machineni S, Berger S, Canadi J, Rajman I, Lloyd P, Pang Y. Safety and tolerability of serelaxin, a recombinant human relaxin-2 in development for the treatment of acute heart failure, in healthy Japanese volunteers and a comparison of pharmacokinetics and pharmacodynamics in healthy Japanese and Caucasian populations. J Clin Pharmacol. 2015 Apr;55(4):415-22

Nonpregnant healthy women: pharmacokinetics of intravaginal relaxin treatment (1 trial, 26 participants)

2. Chen SA, Perlman AJ, Spanski N, Peterson CM, Sanders SW, Jaffe R, Martin M, Yalcinkaya T, Cefalo RC, Chescheir NC, et al. The pharmacokinetics of recombinant human relaxin in nonpregnant women after intravenous, intravaginal, and intracervical administration. Pharm Res. 1993 Jun;10(6):834-8.

Nonpregnant healthy women: pharmacokinetics of 28 days of subcutaneous relaxin (1 trial, ? participants)

3. Stewart DR, Erikson MS, Erikson ME, Nakajima ST, Overstreet JW, Lasley BL, Amento EP, Seppala M. The role of relaxin in glycodelin secretion. J Clin Endocrinol Metab. 1997 Mar;82(3):839-46.

Healthy adults: No effect on tooth movement over 8 weeks of 1x/week alocal inejction of 50 µg of relaxin (1 trial, 40 participants)

4. McGorray SP, Dolce C, Kramer S, Stewart D, Wheeler TT. A randomized, placebo-controlled clinical trial on the effects of recombinant human relaxin on tooth movement and short-term stability. Am J Orthod Dentofacial Orthop. 2012 Feb;141(2):196-203

Cervical ripening and induction of labor in pregnant women: significant effect of intravaginal gel of relaxin (1 trial, 71 participants)

5. MacLennan AH, Green RC, Grant P, Nicolson R. Ripening of the human cervix and induction of labor with intracervical purified porcine relaxin. Obstet Gynecol. 1986 Nov;68(5):598-601

Cervical ripening and induction of labor in pregnant women: significant effect of IV procine relaxin (1 publication, 2 trials, ? participants)

2 trials mentioned in:

6. Evans MI, Dougan MB, Moawad AH, Evans WJ, Bryant-Greenwood GD, Greenwood FC. Ripening of the human cervix with porcine ovarian relaxin. Am J Obstet Gynecol. 1983 Oct 15;147(4):410-4.

Cervical ripening in pregnant women: no significant effect of intravaginal gel of relaxin (4 trials, > 208 participants)

7. Weiss G, Teichman S, Stewart D, Nader D, Wood S, Breining P, Unemori E. Recombinant human relaxin versus placebo for cervical ripening: a double-blind randomised trial in pregnant women scheduled for induction of labour. BMC Pregnancy Childbirth. 2016 Sep 5;16:260
8. Weiss G, Teichman S, Stewart D, Nader D, Wood S, Unemori E. A randomized, double-blind, placebo-controlled trial of relaxin for cervical ripening in post-delivery date pregnancies. Ann N Y Acad Sci. 2009 Apr;1160:385-6.
9. Brennand JE, Calder AA, Leitch CR, Greer IA, Chou MM, MacKenzie IZ. Recombinant human relaxin as a cervical ripening agent. Br J Obstet Gynaecol. 1997 Jul;104(7):775-80.
10. Bell RJ, Permezel M, MacLennan A, Hughes C, Healy D, Brennecke S. A randomized, double-blind, placebo-controlled trial of the safety of vaginal recombinant human relaxin for cervical ripening. Obstet Gynecol. 1993 Sep;82(3):328-33.

IVF in vitro fertilization: no significant effect on pregnancy rate of intravaginal gel of porcine relaxin on the day of embryo transfer (1 trial, 71 participants)

11. MacLennan AH, Kerin JF, Kirby C, Grant P, Warnes GM, Cox LW, Bryant-Greenwood G, Greenwood F. The effect of porcine relaxin vaginally applied at human embryo transfer in an in vitro fertilization program. Aust N Z J Obstet Gynaecol. 1985 Feb;25(1):68-71

Acute heart failure: the improvement with 2 days of relaxin treatment (4 trials, 1504 patients)

12. Sato N, Takahashi W, Hirayama A, Ajioka M, Takahashi N, Okishige K, Wang X, Maki A, Maruyama H, Ebinger U, Yamaguchi M, Pang Y, Matsumoto H, Kawana M. Multicenter, Randomized, Double-Blinded, Placebo-Controlled Phase II Study of Serelaxin in Japanese Patients With Acute Heart Failure. Circ J. 2015;79(6):1237-47.
13. Ponikowski P, Mitrovic V, Ruda M, Fernandez A, Voors AA, Vishnevsky A, Cotter G, Milo O, Laessing U, Zhang Y, Dahlke M, Zymlinski R, Metra M. A randomized, double-blind, placebo-controlled, multicentre study to assess hemodynamic effects of serelaxin in patients with acute heart failure. Eur Heart J. 2014 Feb;35(7):431-41.
14. Teerlink JR, Metra M, Felker GM, Ponikowski P, Voors AA, Weatherley BD, Marmor A, Katz A, Grzybowski J, Unemori E, Teichman SL, Cotter G. Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF): a multicentre, randomized, placebo-controlled, parallel-group, dose-finding phase IIb study. Lancet. 2009 Apr 25;373(9673):1429-39.

1 trial RELAX-AHF: 1161 participants, 7 publications

15. Felker GM, Teerlink JR, Butler J, Hernandez AF, Miller AB, Cotter G, Davison BA, Filippatos G, Greenberg BH, Ponikowski P, Voors AA, Hua TA, Severin TM, Unemori E, Metra M. Effect of serelaxin on mode of death in acute heart failure: results from the RELAX-AHF study. J Am Coll Cardiol. 2014 Oct 14;64(15):1591-8.
16. Filippatos G, Teerlink JR, Farmakis D, Cotter G, Davison BA, Felker GM, Greenberg BH, Hua T, Ponikowski P, Severin T, Unemori E, Voors AA, Metra M. Serelaxin in acute heart failure patients with preserved left ventricular ejection fraction: results from the RELAX-AHF trial. Eur Heart J. 2014 Apr;35(16):1041-50.
17. Metra M, Cotter G, Davison BA, Felker GM, Filippatos G, Greenberg BH, Ponikowski P, Unemori E, Voors AA, Adams KF Jr, Dorobantu MI, Grinfeld L, Jondeau G, Marmor A, Masip J, Pang PS, Werdan K, Prescott MF, Edwards C, Teichman SL, Trapani A, Bush CA, Saini R, Schumacher C, Severin T, Teerlink JR; RELAX-AHF Investigators. Effect of serelaxin on cardiac, renal, and hepatic biomarkers in the Relaxin in Acute Heart Failure (RELAX-AHF) development program: correlation with outcomes. J Am Coll Cardiol. 2013 Jan 15;61(2):196-206.
18. Teerlink JR, Cotter G, Davison BA, Felker GM, Filippatos G, Greenberg BH, Ponikowski P, Unemori E, Voors AA, Adams KF Jr, Dorobantu MI, Grinfeld LR, Jondeau G, Marmor A, Masip J, Pang PS, Werdan K, Teichman SL, Trapani A, Bush CA, Saini R, Schumacher C, Severin TM, Metra M; RELAXin in Acute Heart Failure (RELAX-AHF) Investigators. Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomized, placebo-controlled trial. Lancet. 2013 Jan 5;381(9860):29-39
19. Ponikowski P, Metra M, Teerlink JR, Unemori E, Felker GM, Voors AA, Filippatos G, Greenberg B, Teichman SL, Severin T, Mueller-Velten G, Cotter G, Davison BA. Design of the RELAXin in acute heart failure study. Am Heart J. 2012 Feb;163(2):149-55.e1.
20. Metra M, Ponikowski P, Cotter G, Davison BA, Felker GM, Filippatos G, Greenberg BH, Hua TA, Severin T, Unemori E, Voors AA, Teerlink JR. Effects of serelaxin in subgroups of patients with acute heart failure: results from RELAX-AHF. Eur Heart J. 2013 Oct;34(40):3128-36.

Acute heart and kidney failure: the improvement with 24h of relaxin treatment (817 patients)

21. Liu LC, Voors AA, Teerlink JR, Cotter G, Davison BA, Felker GM, Filippatos G, Chen Y, Greenberg BH, Ponikowski P, Pang PS, Prescott MF, Hua TA, Severin TM, Metra M. Effects of serelaxin in acute heart failure patients with renal impairment: results from RELAX-AHF. Clin Res Cardiol. 2016 Sep;105(9):727-37.

Chronic heart failure: the improvement with relaxin treatment (1 trial, 65 patients)

22. Voors AA, Dahlke M, Meyer S, Stepinska J, Gottlieb SS, Jones A, Zhang Y, Laurent D, Slart RH, Navis GJ. Renal hemodynamic effects of serelaxin in patients with chronic heart failure: a randomized, placebo-controlled study. Circ Heart Fail. 2014 Nov;7(6):994-1002.

Scleroderma: the improvement with 6 weeks of relaxin treatment (2 trials, 98 patients)

23. Seibold JR, Korn JH, Simms R, Clements PJ, Moreland LW, Mayes MD, Furst DE, Rothfield N, Steen V, Weisman M, Collier D, Wigley FM, Merkel PA, Csuka ME, Hsu V, Rocco S, Erikson M, Hannigan J, Harkonen WS, Sanders ME. Recombinant human relaxin in the treatment of scleroderma. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2000 Jun 6;132(11):871-9.
24. Seibold JR, Clements PJ, Furst DE, Mayes MD, McCloskey DA, Moreland LW, White B, Wigley FM, Rocco S, Erikson M, Hannigan JF, Sanders ME, Amento EP. Safety and pharmacokinetics of recombinant human relaxin in systemic sclerosis. J Rheumatol.1998 Feb;25(2):302-7.

Scleroderma: no significant improvement with relaxin treatment, worsening of kidney function after therapy cessation (1 trial, 195 patients)

25. Khanna D, Clements PJ, Furst DE, Korn JH, Ellman M, Rothfield N, Wigley FM, Moreland LW, Silver R, Kim YH, Steen VD, Firestein GS, Kavanaugh AF, Weisman M, Mayes MD, Collier D, Csuka ME, Simms R, Merkel PA, Medsger TA Jr, Sanders ME, Maranian P, Seibold JR; Relaxin Investigators and the Scleroderma Clinical Trials Consortium. Recombinant human relaxin in the treatment of systemic sclerosis with diffuse cutaneous involvement: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2009 Apr;60(4):1102-11

Quality of life: the improvement with relaxin treatment (1 reference)

1. Seibold JR, Clements PJ, Furst DE, Mayes MD, McCloskey DA, Moreland LW, White B, Wigley FM, Rocco S, Erikson M, Hannigan JF, Sanders ME, Amento EP. Safety and pharmacokinetics of recombinant human relaxin in systemic sclerosis. J Rheumatol. 1998 Feb;25(2):302-7.

Premenstrual syndrome: the association with low relaxin levels (1 reference)

1. Pehrsson M, Westberg L, Landén M, Ekman A. Stable serum levels of relaxin throughout the menstrual cycle: a preliminary comparison of women with premenstrual dysphoria and controls. Arch Womens Ment Health. 2007;10(4):147-53.

Dysmenorrhea: the improvement with relaxin treatment (1 reference)

1. Kupperman HS, Rosenberg D, Cutler A. Relaxin in dysmenorrhea and its effect in vitro upon muscular contraction. Ann N Y Acad Sci. 1959 Jan 9;75:1003-10.

Sarcopenia: the improvement with relaxin treatment (2 references)

1. Ferlin A, De Toni L, Sandri M, Foresta C. Relaxin and insulin-like peptide 3 in the musculoskeletal system: from bench to bedside. Br J Pharmacol. 2017 May;174(10):1015-1024.
2. Dehghan F, Haerian BS, Muniandy S, Yusof A, Dragoo JL, Salleh N. The effect of relaxin on the musculoskeletal system. Scand J Med Sci Sports. 2014 Aug;24(4):e220-9

Stretch marks: the association with low relaxin levels (1 reference)

1. Lurie S, Matas Z, Fux A, Golan A, Sadan O. Association of serum relaxin with striae gravidarum in pregnant women. Arch Gynecol Obstet. 2011 Feb;283(2):219-22.

Skin fibrosis: the improvement with relaxin treatment (1 reference)

1. Liu T, Hu XD. Studies on the fibroblast proliferation and transdifferentiation for myofibroblast from skin lesion of the patients with systemic sclerosis repressed by H2 Relaxin. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi.2011 Dec;27(12):1312-4, 1318.

Keloids: the improvement with relaxin treatment (1 reference)

1. Lee WJ, Kim YO, Choi IK, Rah DK, Yun CO. Adenovirus-relaxin gene therapy for keloids: implication for reversing pathological fibrosis. Br J Dermatol. 2011 Sep;165(3):673-7.

Injured ligaments: the improvement with relaxin treatment (1 reference)

1. Ferlin A, De Toni L, Sandri M, Foresta C. Relaxin and insulin-like peptide 3 in the musculoskeletal system: from bench to bedside. Br J Pharmacol. 2017 May;174(10):1015-1024.

Arterial hypertension: the association with low relaxin levels (3 references)

1. Papadopoulos DP, Mourouzis I, Faselis C, Perrea D, Makris T, Tsioufis C, Papademetriou V. Masked hypertension and atherogenesis: the impact of apelin and relaxin plasma levels. J Clin Hypertens (Greenwich). 2013 May;15(5):333-6.
2. Gedikli O, Yilmaz H, Kiris A, Karaman K, Ozturk S, Baykan M, Ucar U, Durmus I, Karahan C, Celik S. Circulating levels of relaxin and its relation to cardiovascular function in patients with hypertension. Blood Press. 2009;18(1-2):68-73.
3. Marshall SA, Senadheera SN, Parry LJ, Girling JE. The role of relaxin in normal and abnormal uterine function during the menstrual cycle and early pregnancy. Reprod Sci. 2017 Mar;24(3):342-354.

Cardiomyopathy: the association with low relaxin levels (1 reference)

1. Nonhoff J, Ricke-Hoch M, Mueller M, Stapel B, Pfeffer T, Kasten M, Scherr M, von Kaisenberg C, Bauersachs J, Haghikia A, Hilfiker-Kleiner D. Serelaxin treatment promotes adaptive hypertrophy but does not prevent heart failure in experimental peripartum cardiomyopathy. Cardiovasc Res. 2017 May 1;113(6):598-608.

Acute heart failure: the improvement with relaxin treatment (10 references)

1. Sato N, Takahashi W, Hirayama A, Ajioka M, Takahashi N, Okishige K, Wang X, Maki A, Maruyama H, Ebinger U, Yamaguchi M, Pang Y, Matsumoto H, Kawana M. Multicenter, Randomized, Double-Blinded, Placebo-Controlled Phase II Study of Serelaxin in Japanese Patients With Acute Heart Failure. Circ J. 2015;79(6):1237-47.
2. Ponikowski P, Mitrovic V, Ruda M, Fernandez A, Voors AA, Vishnevsky A, Cotter G, Milo O, Laessing U, Zhang Y, Dahlke M, Zymlinski R, Metra M. A randomized, double-blind, placebo-controlled, multicentre study to assess haemodynamic effects of serelaxin in patients with acute heart failure. Eur Heart J. 2014 Feb;35(7):431-41.
3. Teerlink JR, Metra M, Felker GM, Ponikowski P, Voors AA, Weatherley BD, Marmor A, Katz A, Grzybowski J, Unemori E, Teichman SL, Cotter G. Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF): a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study. Lancet. 2009 Apr 25;373(9673):1429-39.
4. Felker GM, Teerlink JR, Butler J, Hernandez AF, Miller AB, Cotter G, Davison BA, Filippatos G, Greenberg BH, Ponikowski P, Voors AA, Hua TA, Severin TM, Unemori E, Metra M. Effect of serelaxin on mode of death in acute heart failure: results from the RELAX-AHF study. J Am Coll Cardiol. 2014 Oct 14;64(15):1591-8.
5. Filippatos G, Teerlink JR, Farmakis D, Cotter G, Davison BA, Felker GM, Greenberg BH, Hua T, Ponikowski P, Severin T, Unemori E, Voors AA, Metra M. Serelaxin in acute heart failure patients with preserved left ventricular ejection fraction: results from the RELAX-AHF trial. Eur Heart J. 2014 Apr;35(16):1041-50. 

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Chronic heart failure: the improvement with relaxin treatment (1 reference)

1. Voors AA, Dahlke M, Meyer S, Stepinska J, Gottlieb SS, Jones A, Zhang Y, Laurent D, Slart RH, Navis GJ. Renal hemodynamic effects of serelaxin in patients with chronic heart failure: a randomized, placebo-controlled study. Circ Heart Fail. 2014 Nov;7(6):994-1002.

Systemic sclerosis: the improvement with relaxin treatment (4 references)

1. Kaldas M, Khanna PP, Furst DE, Clements PJ, Kee Wong W, Seibold JR, Postlethwaite AE, Khanna D; investigators of the human recombinant relaxin and oral bovine collagen clinical trials.  Sensitivity to change of the modified Rodnan skin score in diffuse systemic sclerosis–assessment of individual body sites in two large randomized controlled trials. Rheumatology (Oxford). 2009 Sep;48(9):1143-6.
2. Amjadi S, Maranian P, Furst DE, Clements PJ, Wong WK, Postlethwaite AE, Khanna PP, Khanna D; Investigators of the D-Penicillamine, Human Recombinant Relaxin, and Oral Bovine Type I Collagen Clinical Trials. Course of the modified Rodnan skin thickness score in systemic sclerosis clinical trials: analysis of three large multicenter, double-blind, randomized controlled trials. Arthritis Rheum. 2009 Aug;60(8):2490-8.
3. Seibold JR, Korn JH, Simms R, Clements PJ, Moreland LW, Mayes MD, Furst DE, Rothfield N, Steen V, Weisman M, Collier D, Wigley FM, Merkel PA, Csuka ME, Hsu V, Rocco S, Erikson M, Hannigan J, Harkonen WS, Sanders ME. Recombinant human relaxin in the treatment of scleroderma. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2000 Jun 6;132(11):871-9.
4. Seibold JR, Clements PJ, Furst DE, Mayes MD, McCloskey DA, Moreland LW, White B, Wigley FM, Rocco S, Erikson M, Hannigan JF, Sanders ME, Amento EP. Safety and pharmacokinetics of recombinant human relaxin in systemic sclerosis. J Rheumatol.1998 Feb;25(2):302-7.