Evidence-Based Hormone Therapies

Anxiety 

Sedation: the improvement (mild sedation with small, delayed increases in heart rate and feelings of fatigue, and impaired smooth eye pursuit) with a single 200 mg intramuscular injection of progesterone in women in their early follicular phase and in men (1 ref.)

1. Söderpalm AH, Lindsey S, Purdy RH, Hauger R, Wit de H. Administration of progesterone produces mild sedative-like effects in men and women. Psychoneuroendocrinology. 2004 Apr;29(3):339-54.  

Memory

Memory improvement

Cognitive performance and smoking urges: the improvement (in cognitive performances and reduction in smoking urges) with 200 mg/day of oral progesterone for 4 days in abstinent male and female smokers (1 ref.)

2. Sofuoglu M, Mouratidis M, Mooney M. Progesterone improves cognitive performance and attenuates smoking urges in abstinent smokers. 2011 Jan;36(1):123-32.  

No significant effect in cocaine use

Cocaine use: no beneficial effects with 200-600 mg/day of oral progesterone for 10 weeks in men with cocaine user stabilized under methadone (1 ref.) 

3. Sofuoglu M, Poling J, Gonzalez G, Gonsai K, Oliveto A, Kosten TR. Progesterone effects on cocaine use in male cocaine users maintained on methadone: a randomized, double-blind, pilot study. Exp Clin Psychopharmacol. 2007 Oct;15(5):453-60.

Traumatic brain injury

 Acute severe traumatic brain injury: the modest improvement with (100-200 mg/day of)  intramuscular progesterone for 5 days in patients with acute severe traumatic brain injury (1 ref.)

4. Sinha S, Raheja A, Samson N, Goyal K, Bhoi S, Selvi A, Sharma P, Sharma BS. A randomized placebo-controlled trial of progesterone with or without hypothermia in patients with acute severe traumatic brain injury. Neurol India. 2017 Nov-Dec;65(6):1304-11.

Acute severe traumatic brain injury: the improvement (reduction mortality and neurological adverse outcome) with (100-200 mg/day of) intramuscular progesterone (initiated within 8 hours of injury) for 5 days in patients (1 ref.)

5. Xiao G, Wei J, Yan W, Wang W, Lu Z. Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Crit Care. 2008;12(2):R61.

No significant effects on traumatic brain injury

 Traumatic brain injury: no significant beneficial effects (no lower mortality, nor was any improved functional outcome) with intravenous progesterone (initiated within 4 hours of injury) for 4 days in patients with moderate to severe traumatic brain injury (1 ref.)

6. Goldstein FC, Caveney AF, Hertzberg VS, Silbergleit R, Yeatts SD, Palesch YY, Levin HS, Wright DW. Very early administration of progesterone does not improve neuropsychological outcomes in subjects with moderate to severe traumatic brain J Neurotrauma. 2017; 34 (1): Apr 15. Online and N Engl J Med. 2014 Dec 12; 1-10

Traumatic brain injury: no significant beneficial effects (no lower mortality, nor was any improved functional outcome) with intravenous progesterone for 5 days starting within 8 hours after injury in patients with acute traumatic brain injury (1 ref.)

7. Skolnick BE, Maas AI, Narayan RK, van der Hoop RG, MacAllister T, Ward JD, Nelson NR, Stocchetti N; SYNAPSE Trial Investigators. A clinical trial of progesterone for severe traumatic brain injury. N Engl J Med. 2014 Dec 25;371(26):2467-76.

Acute traumatic brain injury: no significant beneficial effects n outcome (no lower mortality, nor was any improved functional outcome)  with intravenous progesterone for 4 days starting  within 4 hours after injury in patients with acute traumatic brain injury (1 ref.)

8. Wright DW, Yeatts SD, Silbergleit R, Palesch YY, Hertzberg VS, Frankel M, Goldstein FC, Caveney AF, Howlett-Smith H, Bengelink EM, Manley GT, Merck LH, Janis LS, Barsan WG; NETT Investigators. Very early administration of progesterone for acute traumatic brain injury. N Engl J Med. 2014 Dec 25;371(26):2457-66

Traumatic spinal cord injury

Traumatic spinal cord injury: the improvement (better functional recovery and outcome) with intramuscular progesterone associated with vitamin D for 5 days treatment in patients (1 ref.)

9. Aminmansour B, Asnaashari A, Rezvani M, Ghaffarpasand F, Amin Noorian SM, Saboori M, Abdollahzadeh P. Effects of progesterone and vitamin D on outcome of patients with acute traumatic spinal cord injury; a randomized, double-blind, placebo-controlled study. J Spinal Cord Med. 2016 May;39(3):272-80.

Calmness, sedation: the improvement with progesterone treatment in men (1 reference)

1. Söderpalm AH, Lindsey S, Purdy RH, Hauger R, Wit de H. Administration of progesterone produces mild sedative-like effects in men and women. Psychoneuroendocrinology. 2004 Apr;29(3):339-54.  

Cognitive performance: the improvement with progesterone treatment in men (1 reference)

1. Sofuoglu M, Mouratidis M, Mooney M. Progesterone improves cognitive performance and attenuates smoking urges in abstinent smokers. 2011 Jan;36(1):123-32.  

Substance abuse (smoking): the improvement with progesterone treatment in men (1 reference)

1. Sofuoglu M, Mouratidis M, Mooney M. Progesterone improves cognitive performance and attenuates smoking urges in abstinent smokers. 2011 Jan;36(1):123-32.

Substance abuse (cocaine): no effect of progesterone treatment in men (1 reference)

1. Sofuoglu M, Poling J, Gonzalez G, Gonsai K, Oliveto A, Kosten TR. Progesterone effects on cocaine use in male cocaine users maintained on methadone: a randomized, double-blind, pilot study. Exp Clin Psychopharmacol. 2007 Oct;15(5):453-60.

Hot flashes: the improvement with progestogen treatment in men (2 references)

1. Langenstroer P, Kramer B, Cutting B, Amling C, Poultan T, Lance R, Thrasher JB. Parenteral medroxyprogesterone for the management of luteinizing hormone releasing hormone induced hot flashes in men with advanced prostate cancer. J Urol. 2005 Aug;174(2):642-5
2. Barton D, Loprinzi C, Quella S, Sloan J, Pruthi S, Novotny P. Depo-medroxy-progesterone acetate for hot flashes. J Pain Symptom Manage. 2002 Dec;24(6):603-7

Sleep disorder: the improvement with progesterone treatment in men (2 references)

1. Oettel M, Mukhopadhyay AK. Progesterone: the forgotten hormone in men? Aging Male. 2004 Sep;7(3):236-57
2. Andersen ML, Bittencourt LR, Antunes IB, Tufik S.152. Effects of progesterone on sleep: a possible pharmacological treatment for sleep-breathing disorders? Curr Med Chem. 2006;13(29):3575-82

Atherosclerosis: the association with lower progesterone levels in men (1 reference)

1. Ma Q, Sun X, Chen Y, Chen X, Zhi G, Tan G. Progesterone levels and carotid intima-media thickness: a negative association in older northern Chinese men. Tex Heart Inst J. 2009;36(4):303-8.

Atherosclerosis: the protective effect of progesterone treatment in men (2 references)

1. Ma Q, Sun X, Chen Y, Chen X, Zhi G, Tan G. Progesterone levels and carotid intima-media thickness: a negative association in older northern Chinese men. Tex Heart Inst J. 2009;36(4):303-8
2. Lee WS, Harder JA, Yoshizumi M, Lee ME, Haber E. Progesterone inhibits arterial smooth muscle cell proliferation. Nat Med. 1997 Sep;3(9):1005-8

Vasodilatation of arteries: increased with progesterone treatment (1 reference)

1. Omar HA, Ramirez R, Gibson M. Properties of a progesterone-induced relaxation in human placental arteries and veins. J Clin Endocrinol Metab. 1995 Feb;80(2):370-3

Obesity: the association with lower progesterone levels in men (1 reference)

1. Blanchette S, Marceau P, Biron S, Brochu G, Tchernof A. Circulating progesterone and obesity in men. Horm Metab Res. 2006 May;38(5):330-5

Diabetes: improvement of arterial alterations with progesterone in men (1 reference)

1. Carmody BJ, Arora S, Wakefield MC, Weber M, Fox CJ, Sidawy AN. Progesterone inhibits human infragenicular arterial smooth muscle cell proliferation induced by high glucose and insulin concentrations. J Vasc Surg. 2002 Oct;36(4):833-8

Rheumatism: the association with lower progesterone levels in men (1 reference)

1. Vogl D, Falk W, Dorner M, Scholmerich J, Straub RH. Serum levels of pregnenolone and 17-hydroxypregnenolone in patients with rheumatoid arthritis and systemic lupus erythematosus: relation to other adrenal hormones. J Rheumatol. 2003 Feb;30(2):269-75.

Kidney impairment: progesterone treatment improves renal excretion of urinary sodium in men (1 reference)

1. Oparil S, Ehrlich EN, Lindheimer MD. Effect of progesterone on renal sodium handling in man: relation to aldosterone excretion and plasma renin activity. Clin Sci Mol Med. 1975 Aug;49(2):139-471

Hair loss: progesterone treatment inhibits the conversion of testosterone to the balding hormone DHT in human hair follicles in men (1 reference)

1. Niiyama S, Happle R, Hoffmann R. Influence of estrogens on the androgen metabolism in different subunits of human hair follicles. Eur J Dermatol. 2001 May-Jun;11(3):195-8

Loss of fertility: progesterone treatment stimulates hypermotility of spermatozoids and fertility of the human sperm in men (9 references)

1. Gonzalez-Martinez MT, Bonilla-Hernandez MA, Guzman-Grenfell AM. Stimulation of voltage-dependent calcium channels during capacitation and by progesterone in human sperm. Arch Biochem Biophys. 2002 Dec 15;408(2):205-10
2. Kay VJ, Coutts JR, Robertson L. Effects of pentoxifylline and progesterone on human sperm capacitation and acrosome reaction. Hum Reprod. 1994 Dec;9(12):2318-23
3. Giojalas LC, Iribarren P, Molina R, Rovasio RA, Estofan D. Determination of human sperm calcium uptake mediated by progesterone may be useful for evaluating unexplained sterility. Fertil Steril. 2004 Sep;82(3):738-40
4. Yang J, Serres C, Philibert D, Robel P, Baulieu EE, Jouannet P. Progesterone and RU486: opposing effects on human sperm. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):529-33
5. Uhler ML, Leung A, Chan SY, Wang C. Direct effects of progesterone and antiprogesterone on human sperm hyperactivated motility and acrosome reaction. Fertil Steril. 1992 Dec;58(6):1191-8

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Synthetically derived progestogens may act as a contraceptive in men (2 references)

1. Handelsman DJ, Conway AJ, Howe CJ, Turner L, Mackey MA. Establishing the minimum effective dose and additive effects of depot progestin in suppression of human spermatogenesis by a testosterone depot. J Clin Endocrinol Metab. 1996 Nov;81(11):4113-21
2. Soufir JC, Jouannet P, Marson J, Soumah A. Reversible inhibition of sperm production and gonadotrophin secretion in men following combined oral medroxyprogesterone acetate and percutaneous testosterone treatment. Acta Endocrinol (Copenh). 1983 Apr;102(4):625-32

Facial nerve injury: the improvement with progesterone treatment (1 reference)

1. Chavez-Delgado ME, Mora-Galindo J, Gomez-Pinedo U, Feria-Velasco A, Castro-Castaneda S, Lopez-Dellamary Toral FA, Luquin-De Anda S, Garcia-Segura LM, Garcia-Estrada J. Facial nerve regeneration through progesterone-loaded chitosan prosthesis. A preliminary report. J Biomed Mater Res B Appl Biomater. 2003 Nov 15;67(2):702-11

Traumatic brain injury: the protective association of higher progesterone levels in men (1 reference)

1. Wright DW, Bauer ME, Hoffman SW, Stein DG. Serum progesterone levels correlate with decreased cerebral edema after traumatic brain injury in male rats. J Neurotrauma. 2001 Sep;18(9):901-9.

Traumatic brain injury: the improvement with progesterone treatment in men (9 references)

1. Sinha S, Raheja A, Samson N, Goyal K, Bhoi S, Selvi A, Sharma P, Sharma BS. A randomized placebo-controlled trial of progesterone with or without hypothermia in patients with acute severe traumatic brain injury. Neurol India. 2017 Nov-Dec;65(6):1304-11.
2. Xiao G, Wei J, Yan W, Wang W, Lu Z. Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Crit Care. 2008;12(2):R61
3. Wright DW, Kellermann AL, Hertzberg VS, Clark PL, Frankel M, Goldstein FC, Salomone JP, Dent LL, Harris OA, Ander DS, Lowery DW, Patel MM, Denson DD, Gordon AB, Wald MM, Gupta S, Hoffman SW, Stein DG. ProTECT: A Randomized Clinical Trial of Progesterone for Acute Traumatic Brain Injury. Ann Emerg Med. 2007 Apr;49(4):391-402, 402.e1-2
4. Cutler SM, Van Landingham JW, Murphy AZ, Stein DG. Slow-release and injected progesterone treatments enhance acute recovery after traumatic brain injury. Pharmacol Biochem Behav. 2006 Jul;84(3):420-8
5. Robertson CL, Puskar A, Hoffman GE, Murphy AZ, Saraswati M, Fiskum G. Physiologic progesterone reduces mitochondrial dysfunction and hippocampal cell loss after traumatic brain injury in female rats. Exp Neurol. 2006 Jan;197(1):235-43

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Traumatic spinal cord injury: the improvement with progesterone associated with vitamin D (1 reference)

1. Aminmansour B, Asnaashari A, Rezvani M, Ghaffarpasand F, Amin Noorian SM, Saboori M, Abdollahzadeh P. Effects of progesterone and vitamin D on outcome of patients with acute traumatic spinal cord injury; a randomized, double-blind, placebo-controlled study. J Spinal Cord Med. 2016 May;39(3):272-80.

Prostate hypertrophy/adenoma: the association of a low progesterone level and a high estradiol (1 reference)

1. Baranowska B, Zgliczynski S, Szymanowski J. Hormonal disturbances in men with a prostatic adenoma. J Urol (Paris). 1980;86(7):551-8

Prostate hypertrophy/adenoma: the improvement with progestogen treatment (1 reference)

1. Onu PE. Depot medroxyprogesterone in the management of benign prostatic hyperplasia. Eur Urol. 1995;28(3):229-35

Benign prostate hypertrophy: the strong subjective and objective improvements with progestogen treatment (1 reference)

1. Apicella F, Romanelli B. [Treatment of prostatic hypertrophy with synthetic progestational hormones]. Minerva Urol. 1971 Sep-Oct;23(5):220-4.  

Benign prostate hypertrophy: the improvement (reduction of growth) with progesterone and progestogens in vitro and in vivo in men (1 reference)

1. Tan SY, Antonipillai I, Murphy BE. Inhibition of testosterone metabolism in the human prostate. J Clin Endocrinol Metab. 1974 Nov;39(5):936-41.  

Benign prostate hypertrophy: the modest subjective improvement with progestogen treatment in vivo (1 reference)

1. Meiraz D, Margolin Y, Lev-Ran A, Lazebnik J. Treatment of benign prostatic hyperplasia with hydroxyprogesterone-caproate: placebo-controlled study. Urology. 1977 Feb;9(2):144-8.

Prostate cancer: the improvement (apoptosis of androgen-sensitive and androgen-insensitive PC cell lines) with progesterone treatment in vitro (4 references)

1. Andrews P, Krygier S, Djakiew D. Dihydrotestosterone (DHT) modulates the ability of NSAIDs to induce apoptosis of prostate cancer cells. Cancer Chemother Pharmacol. 2002 Mar;49(3):179-86
2. Lin MF, Kawachi MH, Stallcup MR, Grunberg SM, Lin FF. Growth inhibition of androgen-insensitive human prostate carcinoma cells by a 19-norsteroid derivative agent, mifepristone. Prostate. 1995 Apr;26(4):194-204
3. Cabeza M, Bratoeff E, Heuze I, Rojas A, Terán N, Ochoa M, Ramírez-Apan T, Ramírez E, Pérez V, Gracia I. New progesterone derivatives as inhibitors of 5alpha-reductase enzyme and prostate cancer cell growth. J Enzyme Inhib Med Chem.2006 Aug;21(4):371-8.
4. Padilla GM, Yacullo RC, Padilla JJ, Payne B, Petrow V. Melengestrol acetate and megestrol acetate are prostatic tumor inhibiting agents. Biochem Cell Biol. 1990 Oct;68(10):1181-8.  

Prostate cancer: the improvement (remission, slowed progression) with progestogen treatment in vivo (3 references)

1. Balducci L, Khansur T, Smith T, Hardy C. Prostate cancer: a model of cancer in the elderly. Arch Gerontol Geriatr. 1989 Mar;8(2):165-87 Bay Pines VAMC, FL 33504
2. Fossa SD, Jahnsen JU, Karlsen S, Ogreid P, Haveland H, Trovag A. High-dose medroxyprogesterone acetate versus prednisolone in hormone-resistant prostatic cancer. A pilot study. Eur Urol. 1985;11(1):11-6
3. Robustelli della Cuna G, Zanon P, Pavesi L, Preti P, Prada GA, Decensi A. An overview of clinical trials with high-dose medroxyprogesterone acetate (HD-MPA) in endocrine-related tumors other than breast cancer. Chemioterapia. 1986 Jun;5(3):164-72.

Metastatic lesions from prostate cancer lesions express no progesterone receptors (1 reference)

1. Hobisch A, Hittmair A, Daxenbichler G, Wille S, Radmayr C, Hobisch-Hagen P, Bartsch G, Klocker H, Culig Z. Metastatic lesions from prostate cancer do not express oestrogen and progesterone receptors. J Pathol. 1997 Jul; 182(3):356-61

Progestogen treatment may induce more subjective remissions of short duration in men with hormone-resistant prostate cancer (1 reference)

1. Fossa SD, Jahnsen JU, Karlsen S, Ogreid P, Haveland H, Trovag A. High-dose medroxyprogesterone acetate versus prednisolone in hormone-resistant prostatic cancer. A pilot study. Eur Urol. 1985;11(1):11-6

Longevity: the improvement with progesterone treatment (1 reference)

1. Wright DW, Kellermann AL, Hertzberg VS, Clark PL, Frankel M, Goldstein FC, Salomone JP, Dent LL, Harris OA, Ander DS, Lowery DW, Patel MM, Denson DD, Gordon AB, Wald MM, Gupta S, Hoffman SW, Stein DG. ProTECT: A Randomized Clinical Trial of Progesterone for Acute Traumatic Brain Injury. Ann Emerg Med. 2007 Apr;49(4):391-402, 402.e1-2