Progesterone is a term that is incorrectly used interchangeably to describe both natural bio-identical progesterone and synthetic substitutes. Synthetic progestins (also called progestogens or progestational agents) are derivatives of bio-identical progesterone, and have been developed because they are longer lasting, more potent and patentable. Although synthetic progestins such as medroxy-progesterone acetate are clearly beneficial in preventing estrogen-induced overgrowth of the uterine lining and endometrial cancer, their other effects are less desirable.

Below we see the difference in bio-identical progesterone and Provera® (medroxyprogestone), a synthetic progestin. The synthetic progestins are not the same and they have different actions in the body than the hormones they are intended to replace.

Progesterone – General

Psychopharmacology (Berl). 1999 Mar;143(1):29-38.
Assessment of neuroleptic-like properties of progesterone.
Rupprecht R, Koch M, Montkowski A, Lancel M, Faulhaber J, Harting J, Spanagel R.
Max Planck Institute of Psychiatry, Clinical Institute, Munich, Germany.

Clin Ther. 1999 Jan;21(1):41-60; discussion 1-2.
Oral micronized progesterone.
de Lignieres B.
Department of Endocrinology and Reproductive Medicine, Hopital Necker, Paris, France

Compr Ther. 1998 Jun-Jul;24(6-7):336-9.
Differentiating between natural progesterone and synthetic progestins: clinical implications for premenstrual syndrome and perimenopause management.
Martorano JT, Ahlgrimm M, Colbert T.
PMS Medical Center, New York, NY 10022, USA.

Fertil Steril. 1994 Sep;62(3):485-90.
Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes: a comparative study.
Miles RA, Paulson RJ, Lobo RA, Press MF, Dahmoush L, Sauer MV.
Department of Obsetetrics and Gynecology, University of Southern California School of Medicine, Los Angeles.

Fertil Steril. 2003 Jan;79(1):221-2.
Topical progesterone cream has an antiproliferative effect on estrogen-stimulated endometrium.
Leonetti HB, Wilson KJ, Anasti JN.

Maturitas. 1994 Aug;19(2):103-15.
Induction of amenorrhea during hormone replacement therapy: optimal micronized progesterone dose. A multicenter study.
Gillet JY, Andre G, Faguer B, Erny R, Buvat-Herbaut M, Domin MA, Kuhn JM, Hedon B, Drapier-Faure E, Barrat J, et al.
Department of Gynecology and Obstetrics of Saint Roch Hospital, Nice, France.

Hum Reprod Update. 2000 Mar-Apr;6(2):139-48.
Comparison between different routes of progesterone administration as luteal phase support in infertility treatments.
Tavaniotou A, Smitz J, Bourgain C, Devroey P.
Centre for Reproductive Mediciney, Dutch-Speaking Free University of Brussels, Belgium.

Obstet Gynecol. 1999 Aug;94(2):225-8.
Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss.
Leonetti HB, Longo S, Anasti JN.
Department of Obstetric and Gynecology, St. Luke's Hospital, Bethlehem, Pennsylvania 18015, USA.

Am J Obstet Gynecol. 1999 Jun;180(6 Pt 1):1504-11.
Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen.
Burry KA, Patton PE, Hermsmeyer K.
Department of Obstetrics, Oregon Health Sciences University, Portland, USA.

Clin Endocrinol (Oxf). 2000 Nov;53(5):615-20.
Salivary, but not serum or urinary levels of progesterone are elevated after topical application of progesterone cream to pre-and postmenopausal women.
O'Leary P, Feddema P, Chan K, Taranto M, Smith M, Evans S.
Biochemistry Department, Royal Perth Hospital, Western Australia, Australia.

Progesterone – Bone

Endocr Rev. 1990 May;11(2):386-98.
Progesterone as a bone-trophic hormone.
Prior JC.
Division of Endocrinology and Metabolism, University of British Columbia, Vancouver, Canada.

Calcif Tissue Int. 1983 Jul;35(4-5):609-14.
Influence of estrogen and progesterone on matrix-induced endochondral bone formation.
Burnett CC, Reddi AH.

J Bone Miner Res. 1990 Nov;5(11):1143-7.
Effects of progesterone on postovariectomy bone loss in aged rats.
Barengolts EI, Gajardo HF, Rosol TJ, D'Anza JJ, Pena M, Botsis J, Kukreja SC.
Department of Medicine, VA West Side Medical Center, Chicago, IL.

Ann Med. 2000 Dec;32(9):608-14.
The replacement of oestradiol and progesterone in very premature infants.
Trotter A, Pohlandt F.
Section of Neonatology and Pediatric Critical Care Medicine, Children's Hospital, University of Ulm, Germany.

Progesterone – Cardiovascular/Liver

Gynecol Endocrinol. 1993 Jun;7(2):111-4.
Liver metabolism during treatment with estradiol and natural progesterone.
Darj E, Axelsson O, Carlstrom K, Nilsson S, von Schoultz B.
Department of Obstetrics and Gynecology, Uppsala University, Sweden.

J Clin Endocrinol Metab. 1999 Jan;84(1):265-71.
Two antiatherogenic effects of progesterone on human macrophages; inhibition of cholesteryl ester synthesis and block of its enhancement by glucocorticoids.
Cheng W, Lau OD, Abumrad NA.
Department of Physiology and Biophysics, State University of New York at Stony Brook, 11794-8661, USA.

J Vasc Surg. 2002 Oct;36(4):833-8.
Progesterone inhibits human infragenicular arterial smooth muscle cell proliferation induced by high glucose and insulin concentrations.
Carmody BJ, Arora S, Wakefield MC, Weber M, Fox CJ, Sidawy AN.
Department of Surgery, Veterans Affairs Medical Center, Walter Reed Army Medical Center, USA.

J Clin Endocrinol Metab. 1999 Jan;84(1):265-71.
Progestogens and cardiovascular disease. A critical review.
Clarkson TB.
Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Medicine Center Boulevard, Winston-Salem, NC 27157-1040, USA.

J Am Coll Cardiol. 2000 Dec;36(7):2154-9.
Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women.
Rosano GM, Webb CM, Chierchia S, Morgani GL, Gabraele M, Sarrel PM, de Ziegler D, Collins P.
Department of Cardiology, Ospedale San Raffaele, Rome, Italy.

Exp Physiol. 2001 Jan;86(1):101-8.
The effect of progesterone on coronary blood flow in anaesthesized pigs.
Molinari C, Battaglia A, Grossini E, Mary DA, Stoker JB, Surico N, Vacca G.
Laboratorio de Fisiologia, Dipartimento di Scienze Mediche, Facolta di Medicina e Chirurgia di Novara, Universita del Piemonte Orientale A. Avogadro, via Solaroli 17, I-28100 Novara, Italy.

Nat Med. 1997 Sep;3(9):1005-8.
Progesterone inhibits arterial smooth muscle cell proliferation.
Lee WS, Harder JA, Yoshizumi M, Lee ME, Haber E.
Cardiovascular Biology Laboratory, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

Br Med J (Clin Res Ed). 1985 Jan 5;290(6461):13-4.
Natural progesterone and antihypertensive action.
Rylance PB, Brincat M, Lafferty K, De Trafford JC, Brincat S, Parsons V, Studd JW.

Progesterone – Central Nervous Syste

Am J Obstet Gynecol. 1988 Nov;159(5):1203-9.
Sedative and hypnotic effects of oral administration of micronized progesterone may be mediated through its metabolites.
Arafat ES, Hargrove JT, Maxson WS, Desiderio DM, Wentz AC, Andersen RN.
Science and Mathematics Division, Rust College, Holly Springs, Memphis. Neuroendocrinology. 1993 Oct;58(4):478-84.
Anxiolytic metabolites of progesterone: correlation with mood and performance measures following oral progesterone administration to healthy female volunteers.
Freeman EW, Purdy RH, Coutifaris C, Rickels K, Paul SM.
Department of Obstetrics/Gynecology, University of Pennsylvania, Philadelphia

Psychoneuroendocrinology. 2003 Feb;28(2):139-68.
Neuroactive steroids: mechanisms of action and neuropsychopharmacological properties.
Rupprecht R.

Department of Psychiatry, Ludwig Maximilian University, Munich, Germany.

Science. 1995 Jun 9;268(5216):1500-3.
Progesterone synthesis and myelin formation by Schwann cells.
Koenig HL, Schumacher M, Ferzaz B, Thi AN, Ressouches A, Guennoun R, Jung-Testas I, Robel P, Akwa Y, Baulieu EE.
Laboratoire Neurobiologie du Developpement, Universite Bordeaux I, Talence, France. Menopause. 2001 Jan-Feb;8(1):10-6.
Sleep in menopause: differential effects of two forms of hormone replacement therapy.
Montplaisir J, Lorrain J, Denesle R, Petit D.
Centre d'etude du sommeil, H pital du Sacre-Coeur de Montreal and Department of Psychiary, Universite de Montreal, Quebec, Canada. Mult Scler. 1997 Apr;3(2):105-12.
Neurosteroids, with special reference to the effect of progesterone on myelination in peripheral nerves.
Baulieu EE, Schumacher M.
INSERM U 33, Le Kremlin-Bicetre, France.