Progesterone

Progesterone is produced in the ovaries of ovulating women and in the placenta during pregnancy. Progesterone peaks in the last two weeks of the menstrual cycle preparing the lining of the uterus for implantation of the fertilized ovum. If no implantation occurs, progesterone levels drop, menstruation occurs and another cycle begins.

During the second half of the menstrual cycle progesterone balances the stimulatory effects of estrogen. If progesterone is deficient or estrogen is dominant, premenstrual syndrome (PMS) can occur with associated symptoms such as bloating, irritability, headaches, heavy painful periods and breast tenderness.

During early pregnancy, the placenta produces progesterone which assists in maintaining the pregnancy. The daily amount of progesterone secreted during pregnancy is 10-20 times greater than that of the luteal phase of a normal menstrual cycle. The increased levels of progesterone during pregnancy are known to act as a serenity hormone, lessening worry and bringing a sense of peace.

Progesterone is NOT the same as a Progestin

It is important to note that progestogens such as medroxyprogesterone acetate (MPA) are not the same as progesterone; they are synthetic patentable derivatives of progesterone that have divergent effects in the body and different risk profiles [1, 2].

Since results of the Women’s Health Initiative Trial and the Million Women’s Study have been published, which used synthetic progestogens, there has been a tendency to overlook the difference between the two types of molecules and to consider progesterone to be as dangerous as progestogens. As a consequence, most women and in some cases physicians, have no idea of the differences between progestogens (synthetic) and progesterone (natural). This is vitality important given the disparity between the molecules and the lack of risk and adverse symptoms attributed to progesterone, compared to chemically altered progestogens.

The intention behind bio identical hormone supplementation with natural or bio identical progesterone is to supply the exact copy of the hormone produced in the body, at physiological levels, mimicking the timing of hormone production that normally occurs in our bodies. For further information on progesterone dosing, click here.

1a) Conditions which May Benefit from Progesterone Supplementation

• Amenorrhea [3]
• Anxiety [4]
• Breast tenderness and benign breast disease (specifically cyclical) [5]
• Breast cancer [6-11]
• Depression [4, 12]
• Endometrial hyperplasia and endometriosis [13]
• Fluid retention [14]
• Hot flashes / Hot flushes/ Night sweats [15]
• Infertility [16, 17]
• Insomnia [18-20]
• Menopausal symptoms [15]
• Migraines [14, 21]
• Mood swings [4]
• Osteoporosis [22, 23]
• Painful irregular heavy menstruation [13]
• Polycystic ovarian syndrome [24, 25]
• Post natal depression [12, 26, 27]
• Premenstrual syndrome (PMS) [4]
• Recurrent miscarriages [16, 17]
• Traumatic brain injury [28, 29]
• Tubal ligation induced progesterone deficiency [30]
• Vulvar dystrophy [31, 32]

1b) Benefits from Progesterone Supplementation

• Improved skin elasticity and reduced wrinkles [33]
• Improved sleep, mood, memory & concentration [4, 18-20]
• Prevention of osteoporosis & restoration of lost bone (when used with essential nutrients) [22, 23]
• Protection against heart disease & stroke [34, 35]
• Reduced risk of cancer of the breast, uterus & ovaries [6-9, 36, 37]

References:

1.         Rosano, G.M., et al., Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women. J Am Coll Cardiol, 2000. 36(7): p. 2154-9.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11127455
2.         Simoncini, T., et al., In vitro effects of progesterone and progestins on vascular cells. Steroids, 2003. 68(10-13): p. 831-6.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14667975
3.         Genazzani, A.D., et al., Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea. J Steroid Biochem Mol Biol, 2001. 78(3): p. 247-52.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11595505
4.         Baker, E.R., et al., Efficacy of progesterone vaginal suppositories in alleviation of nervous symptoms in patients with premenstrual syndrome. J Assist Reprod Genet, 1995. 12(3): p. 205-9.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8520187
5.         Nappi, C., et al., Double-blind controlled trial of progesterone vaginal cream treatment for cyclical mastodynia in women with benign breast disease. J Endocrinol Invest, 1992. 15(11): p. 801-6.
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6.         Bu, S.Z., et al., Progesterone induces apoptosis and up-regulation of p53 expression in human ovarian carcinoma cell lines. Cancer, 1997. 79(10): p. 1944-50.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9149021
7.         Cowan, L.D., et al., Breast cancer incidence in women with a history of progesterone deficiency. Am J Epidemiol, 1981. 114(2): p. 209-17.
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8.         Formby, B. and T.S. Wiley, Progesterone inhibits growth and induces apoptosis in breast cancer cells: inverse effects on Bcl-2 and p53. Ann Clin Lab Sci, 1998. 28(6): p. 360-9.
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9.         Kaaks, R., et al., Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst, 2005. 97(10): p. 755-65.
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10.       Chang, K.J., et al., Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo. Fertil Steril, 1995. 63(4): p. 785-91.
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11.       Mohr, P.E., et al., Serum progesterone and prognosis in operable breast cancer. Br J Cancer, 1996. 73(12): p. 1552-5.
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12.       Kaura, V., et al., The progesterone metabolite allopregnanolone potentiates GABA(A) receptor-mediated inhibition of 5-HT neuronal activity. Eur Neuropsychopharmacol, 2006.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16574382
13.       Affinito, P., et al., Endometrial hyperplasia: efficacy of a new treatment with a vaginal cream containing natural micronized progesterone. Maturitas, 1994. 20(2-3): p. 191-8.
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14.       Watanabe, H., et al., Effect of progesterone therapy on arginine vasopressin and atrial natriuretic factor in premenstrual syndrome. Clin Invest Med, 1997. 20(4): p. 211-23.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9258576
15.       Leonetti, H.B., S. Longo, and J.N. Anasti, Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss. Obstet Gynecol, 1999. 94(2): p. 225-8.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10432132
16.       Walker, S., et al., The role of salivary progesterone in studies of infertile women. Br J Obstet Gynaecol, 1981. 88(10): p. 1009-15.
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17.       Tempfer, C.B., et al., A combination treatment of prednisone, aspirin, folate, and progesterone in women with idiopathic recurrent miscarriage: a matched-pair study. Fertil Steril, 2006. 86(1): p. 145-8.
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18.       Montplaisir, J., et al., Sleep in menopause: differential effects of two forms of hormone replacement therapy. Menopause, 2001. 8(1): p. 10-6.
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19.       Soderpalm, A.H., et al., Administration of progesterone produces mild sedative-like effects in men and women. Psychoneuroendocrinology, 2004. 29(3): p. 339-54.
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20.       Gruber, C.J. and J.C. Huber, Differential effects of progestins on the brain. Maturitas, 2003. 46 Suppl 1: p. S71-5.
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21.       Martin, V.T., et al., Defining the relationship between ovarian hormones and migraine headache. Headache, 2005. 45(9): p. 1190-201.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16178949
22.       Lydeking-Olsen, E., et al., Soymilk or progesterone for prevention of bone loss--a 2 year randomized, placebo-controlled trial. Eur J Nutr, 2004. 43(4): p. 246-57.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15309425
23.       Prior, J.C., Progesterone as a bone-trophic hormone. Endocr Rev, 1990. 11(2): p. 386-98.
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24.       Meenakumari, K.J., et al., Effects of metformin treatment on luteal phase progesterone concentration in polycystic ovary syndrome. Braz J Med Biol Res, 2004. 37(11): p. 1637-44.
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25.       Unfer, V., et al., Different routes of progesterone administration and polycystic ovary syndrome: a review of the literature. Gynecol Endocrinol, 2005. 21(2): p. 119-27.
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26.       Nappi, R.E., et al., Serum allopregnanolone in women with postpartum "blues". Obstet Gynecol, 2001. 97(1): p. 77-80.
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27.       Gilbert Evans, S.E., et al., 3alpha-reduced neuroactive steroids and their precursors during pregnancy and the postpartum period. Gynecol Endocrinol, 2005. 21(5): p. 268-79.
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28.       Roof, R.L., et al., Progesterone rapidly decreases brain edema: treatment delayed up to 24 hours is still effective. Exp Neurol, 1996. 138(2): p. 246-51.
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29.       Roof, R.L., S.W. Hoffman, and D.G. Stein, Progesterone protects against lipid peroxidation following traumatic brain injury in rats. Mol Chem Neuropathol, 1997. 31(1): p. 1-11.
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30.       Sumiala, S., et al., Salivary progesterone concentrations after tubal sterilization. Obstet Gynecol, 1996. 88(5): p. 792-6.
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31.       Jasionowski, E.A. and P.A. Jasionowski, Further observations on the effect of topical progesterone on vulvar disease. Am J Obstet Gynecol, 1979. 134(5): p. 565-7.
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32.       Jasionowski, E.A. and P. Jasionowski, Topical progesterone in treatment of vulvar dystrophy: preliminary report of five cases. Am J Obstet Gynecol, 1977. 127(6): p. 667-70.
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33.       Holzer, G., et al., Effects and side-effects of 2% progesterone cream on the skin of peri- and postmenopausal women: results from a double-blind, vehicle-controlled, randomized study. Br J Dermatol, 2005. 153(3): p. 626-34.
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34.       Hermsmeyer, R.K., et al., Prevention of coronary hyperreactivity in preatherogenic menopausal rhesus monkeys by transdermal progesterone. Arterioscler Thromb Vasc Biol, 2004. 24(5): p. 955-61.
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35.       Miyagawa, K., et al., Medroxyprogesterone interferes with ovarian steroid protection against coronary vasospasm. Nat Med, 1997. 3(3): p. 324-7.
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36.       Lemon, H.M. and J.F. Rodriguez-Sierra, Timing of breast cancer surgery during the luteal menstrual phase may improve prognosis. Nebr Med J, 1996. 81(4): p. 110-5.
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37.       Plu-Bureau, G., et al., Percutaneous progesterone use and risk of breast cancer: results from a French cohort study of premenopausal women with benign breast disease. Cancer Detect Prev, 1999. 23(4): p. 290-6.
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