Progesterone is a hormone produced by the ovaries and adrenal glands, and it functions to balance the effects of estrogen. Natural progesterone enhances the action of estrogen, as these hormones work together to maintain a normal hormone balance. A lack of progesterone causes disease processes similar to those caused by a deficiency of estrogen. They include osteoporosis, heart disease, decrease in libido, and a significantly diminished quality of life. The combination of natural progesterone and estrogen can prevent this downward spiral by keeping women vital, strong, and healthy. The ovaries begin producing progesterone around puberty, and the monthly ebb and flow of this hormone, in harmony with estrogen and other hormones, continues until menopause. Progesterone’s primary role during this moment is to help make the uterus ready for implantation of a new embryo, the first major event – after fertilization of the egg – in the nine months of human gestation. If the egg is not fertilized, progesterone production temporarily ceases, and the uterus sheds its endometrial lining.

Benefits of Progesterone Replacement

• Precursor to the sex hormones (estrogen and testosterone)¹
• Maintains uterine lining²
• Promotes the survival of the embryo and fetus throughout gestation^3-5
• Supports hormonal balance supporting breast tissue against fibrocystic breasts⁶
• Natural diuretic⁷
• Supports healthy moods by itself and when balanced with other hormones^8-14
• Aids thyroid hormone action^15-18
• Supports healthy blood clotting^19-21
• Supports a healthy brain and neuroplasticity^22-28
• Helps healthy blood sugar levels^29-34
• Protects against abnormal cell development in the endometrium and breast tissue^35-40
• Sustains strong bones^41-43

Side Effects

There are no side effects associated with natural progesterone. However, women who are estrogen-dominant may experience premenstrual mood swings, depression, breast swelling, heavy or irregular periods, and sleep disturbances. If a dose of progesterone is missed, a woman may experience menstrual bleeding.

Administration

Natural progesterone comes in many forms, most commonly a topical cream, an oral capsule, and a sublingual tablet. Progesterone’s half-life is approximately eight hours, which results in the need to take natural progesterone twice a day. Progesterone levels should be measured by a physician to ensure levels are in a therapeutic range.

Related Articles:

• The Primary Roles of Sex Hormones

References:

1. Imataka H, et al. Biosynthetic pathways of testosterone and estradiol-17 beta in slices of the embryonic ovary and testis of the chicken (Gallus domesticus). Gen Comp Endocrinol. 1989 Jan;73(1):69-79.
2. Csapo AI, Pinto-Dantas CA. The effect of progesterone on the human uterus. Proc Natl Acad Sci U S A. 1965 October; 54(4): 1069–1076.
3. Halasz M, Szekeres-Bartho J. The role of progesterone in implantation and trophoblast invasion. J Reprod Immunol. 2013 Mar;97(1):43-50.
4. Spencer TE, Bazer FW. Biology of progesterone action during pregnancy recognition and maintenance of pregnancy. Front Biosci. 2002 Sep 1;7:d1879-98.
5. Kumar P, Magon N. Hormones in pregnancy. Niger Med J. 2012 Oct;53(4):179-83.
6. Thalabard JC, et al. Endocrine markers in benign breast diseases]. Zentralbl Gynakol. 1986;108(6):354-8.
7. Couette B, et al. Aldosterone antagonists destabilize the mineralocorticosteroid receptor. Biochem J. 1992 Mar 15;282 ( Pt 3):697-702.
8. Kulkarni J, et al. A pilot study of hormone modulation as a new treatment for mania in women with bipolar affective disorder. Psychoneuroendocrinology. 2006 May;31(4):543-7.
9. Chouinard G, et al. Estrogen-progesterone combination: another mood stabilizer? Am J Psychiatry. 1987 Jun;144(6):826.
10. Huang MC, et al. Estrogen-progesterone combination for treatment-refractory post-partum mania. Psychiatry Clin Neurosci. 2008 Feb;62(1):126.
11. Frye CA. Progesterone attenuates depressive behavior of younger and older adult C57/BL6, wildtype, and progesterone receptor knockout mice. Pharmacol Biochem Behav. 2011 Oct;99(4):525-31.
12. Carta MG, et al. GABAergic neuroactive steroids: a new frontier in bipolar disorders? Behav Brain Funct. 2012 Dec 19;8:61. doi
13. Valenzuela SK. The power of natural progesterone: treating hormone-related postpartum depression. Midwifery Today Int Midwife. 2012 Autumn;(103):22-5.
14. Schwartz E, Holtorf K. Hormone replacement therapy in the geriatric patient: current state of the evidence and questions for the future. Estrogen, progesterone, testosterone, and thyroid hormone augmentation in geriatric clinical practice: part 1. Clin Geriatr Med. 2011 Nov;27(4):541-59.
15. Kumar P, Magon N. Hormones in pregnancy. Niger Med J. 2012 Oct;53(4):179-83.
16. Jahagirdar V, et al. Maternal hypothyroidism decreases progesterone receptor expression in the cortical subplate of foetal rat brain. J Neuroendocrinol. 2012 Aug;24(8):1126-34.
17. Szelényi Z, Péczely P. Thyroxin induced moult in domestic hen. Acta Physiol Hung. 1988;72(2):143-9.
18. Leers J, et al. A thyroid hormone receptor-dependent glucocorticoid induction. Mol Endocrinol. 1994 Apr;8(4):440-7.
19. Kaibara M, et al. Effect of high-dose progestogen on hemostatic properties of blood in patients with endometrial cancer. Clin Hemorheol Microcirc. 2001;24(2):93-9.
20. Matsuoka T, et al. Effects of restricted feeding on fetal and placental development in pregnant rabbits. J Toxicol Sci. 2012 Feb;37(1):207-14.
21. Henriquez S, et al. Progesterone utilizes distinct membrane pools of tissue factor to increase coagulation and invasion and these effects are inhibited by TFPI. J Cell Physiol. 2011 Dec;226(12):3278-85.
22. Singh M, et al. Non-genomic mechanisms of progesterone action in the brain. Front Neurosci. 2013 Sep 19;7:159.
23. Singh M, et al. Estrogens and progesterone as neuroprotectants: what animal models teach us. Front Biosci. 2008 Jan 1;13:1083-9.
24. Balasubramanian B, et al. (2008). Nonclassical mechanisms of progesterone action in the brain: II. Role of calmodulin-dependent protein kinase II in progesterone-mediated signaling in the hypothalamus of female rats. Endocrinology 149, 5518–5526.
25. Liu B., Arbogast L. A. (2009). Gene expression profiles of intracellular and membrane progesterone receptor isoforms in the mediobasal hypothalamus during pro-oestrus. J. Neuroendocrinol. 21, 993–1000.
26. Intlekofer KA, Petersen SL. Distribution of mRNAs encoding classical progestin receptor, progesterone membrane components 1 and 2, serpine mRNA binding protein 1, and progestin and ADIPOQ receptor family members 7 and 8 in rat forebrain. Neuroscience. 2011 Jan 13;172:55-65.
27. Jodhka PK, et al. The differences in neuroprotective efficacy of progesterone and medroxyprogesterone acetate correlate with their effects on brain-derived neurotrophic factor expression. Endocrinology. 2009 Jul;150(7):3162-8.
28. Cai W, et al. Two different molecular mechanisms underlying progesterone neuroprotection against ischemic brain damage. Neuropharmacology. 2008 Aug;55(2):127-38.
29. Castrogiovanni D, et al. Fructose rich diet-induced high plasminogen activator inhibitor-1 (PAI-1) production in the adult female rat: protective effect of progesterone. Nutrients. 2012 Aug;4(8):1137-50.
30. Flock GB, et al. Activation of enteroendocrine membrane progesterone receptors promotes incretin secretion and improves glucose tolerance in mice. Diabetes. 2013 Jan;62(1):283-90.
31. Ordóñez P, et al. 17beta-Estradiol and/or progesterone protect from insulin resistance in STZ-induced diabetic rats. J Steroid Biochem Mol Biol. 2008 Sep;111(3-5):287-94.
32. Ordóñez P, et al. Insulin sensitivity in streptozotocin-induced diabetic rats treated with different doses of 17beta-oestradiol or progesterone. Exp Physiol. 2007 Jan;92(1):241-9.
33. Moorthy K, et al. Effect of estradiol and progesterone treatment on carbohydrate metabolizing enzymes in tissues of aging female rats. Biogerontology. 2004;5(4):249-59.
34. Bagis T, et al. The effects of short-term medroxyprogesterone acetate and micronized progesterone on glucose metabolism and lipid profiles in patients with polycystic ovary syndrome: a prospective randomized study. J Clin Endocrinol Metab. 2002 Oct;87(10):4536-40.
35. Formby B, Wiley TS. Progesterone inhibits growth and induces apoptosis in breast cancer cells: inverse effects on Bcl-2 and p53. Ann Clin Lab Sci. 1998; 28(6):360–369.
36. Pasqualini JR. Differential effects of progestins on breast tissue enzymes. Maturitas. 2003 Dec 10;46 Suppl 1:S45-54.
37. Campagnoli C, et al. Progestins and progesterone in hormone replacement therapy and the risk of breast cancer. J Steroid Biochem Mol Biol. 2005; 96(2):95-108.
38. Fournier A, et al. Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort. Int J Cancer. 2005; 114:448–454.
39. Pasqualini JR. Differential effects of progestins on breast tissue enzymes. Maturitas. 2003; 46(1):45-54.
40. Moise M, et al. Immunohistochemical profile of the estrogen and progesterone receptors in mammary benign lesions. Rev Med Chir Soc Med Nat Iasi. 2012 Jul-Sep;116(3):875-82.
41. Singh M, et al. Non-genomic mechanisms of progesterone action in the brain. Front Neurosci. 2013 Sep 19;7:159.
42. Seifert-Klauss V, Prior JC. Progesterone and bone: actions promoting bone health in women. J Osteoporos. 2010 Oct 31;2010:845180.
43. Clark AP, Schuttinga JA. Targeted estrogen/progesterone replacement therapy for osteoporosis: calculation of health care cost savings. Osteoporos Int. 1992 Jul;2(4):195-200.