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Categories available are: Androgens; Estrogens; Progesterone; Bone: Brain; Breast; Cardiovascular; Formulations; Menopausal Symptoms; Premenopause; Progestin; Safety; Uterus.
1. - The Bioidentical Hormone Debate: Are Bioidentical Hormones (Estradiol, Estriol, and Progesterone) Safer or More Efficacious than Commonly Used Synthetic Versions in Hormone Replacement Therapy? Holtorf K.
Postgrad Med 2009;121(1):1-13.
This literature review presents the substantial evidence for the safety and efficacy of bioidentical hormone therapy, including estradiol, estriol, and progesterone, which shows that it presents lower risks for breast cancer and Cardiovascular disease than synthetic or animal-derived hormones. Studies show that progestins have a number of negative effects on the cardiovascular system and an association with breast cancer risk that can be avoided by using bioidentical progesterone.
Not available on Pubmed
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2. - The safety of 52 weeks of oral DHEA therapy for postmenopausal women. Panjari M, Bell RJ, Jane F, Adams J, Morrow C, Davis SR.
Maturitas. 2009; 63(3):240-5.
In this study, 93 postmenopausal women received either 50 mg/day DHEA or placebo for 52 weeks. No significant changes, either beneficial or adverse, were seen in the lipid profile (HDL, LDL, total cholesterol and triglycerides), the endometrium, or development of insulin resistance (fasting glucose, fasting insulin, or HOMA-IR).
Article on Pubmed
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3. - Cardiovascular effects of medroxyprogesterone acetate and progesterone: a case of mistaken identity? Hermsmeyer RK, Thompson TL, Pohost GM, Kaski JC.
Nat Clin Pract Cardiovasc Med 2008;5(7):387-95.
The authors present the current state of knowledge about the Cardiovascular effects of progesterone compared to medroxyprogesterone acetate (MPA). They caution that the beneficial effects of natural progesterone on cardiovascular risk have been obscured by the negative results of large trials involving hormone therapy that included MPA, in which cardiac risk was seen to increase. The review covers the evidence that natural progesterone actually improves cardiovascular function, and compares oral and transdermal delivery.
Article on Pubmed
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4. - Transdermal progesterone: effects on menopausal symptoms and on thrombotic, anticoagulant, and inflammatory factors in postmenopausal women. Stephenson K, Neuenschwander PF, Kurdowska AK, Pinson B, Price C.
Int J Pharm Compounding 2008;12(4):295-304.
In this randomized, placebo-controlled, double-blinded, crossover study, 30 postmenopausal women received either 20 mg/day transdermal progesterone or placebo for 4 weeks. Menopausal symptoms were significantly improved by the progesterone treatment compared to placebo, and no detrimental effects on any of the clotting or inflammatory factors were seen. This is in contrast to conventional hormone replacement with conjugated equine estrogens and synthetic progestins, which have been found to increase risk of thrombosis and inflammation and thereby impact Cardiovascular risk. The authors conclude that transdermal progesterone is a safe alternative for the treatment of menopausal symptoms.
Link to Abstract
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5. - Hormone therapy and risk of myocardial infarction: a national register study. Lokkegaard E, Andreasen AH, Jacobsen RK, Nielsen LH, Agger C, Lidegaard O.
Eur Heart J 2008;29(21):2660-8.
This large population study of Danish postmenopausal women found that transdermal estrogen therapy was associated with a significantly lower risk of myocardial infarction than oral unopposed estrogen therapy amongst those using hormone replacement therapy (HRT). The risk of myocardial infarction increased with longer duration of HRT in younger but not older women. A continuous HRT regimen resulted in the greatest risk of myocardial infarction in all age groups, while no increased risk compared to non-HRT users was seen for unopposed estrogen, cyclic estrogen/progestogen HRT, or tibolone. The type of progestogen or dose of estrogen did not appear to affect risk.
Article on Pubmed
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6. - Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis. Canonico M, Plu-Bureau G, Lowe GD, Scarabin PY.
BMJ 2008;336(7655):1227-31
This meta-analysis of 17 studies of postmenopausal women found that those using oral estrogens had an increased risk of thromboembolism compared with those using transdermal estrogens, particularly during the first year of treatment. Even in women with pre-existing risk factors for thromboembolism, transdermal estrogen use did not confer additional risk.
Article on Pubmed
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7. - Is Bio-Identical Hormone Replacement Therapy Safer than Traditional Hormone Replacement Therapy? A Critical Appraisal of Cardiovascular Risks in Menopausal Women. Curcio JJ, Wollner DA, Schmidt JW, Kim LS.
Treat Endocrinol. 2006;5(6):367-374.
This review examines currently used bioidentical hormones used as alternatives to conventional hormone replacement therapy. The authors acknowledge that the clinical evidence shows natural progesterone to be superior to synthetic progestins, because of its more beneficial effects on lipids, the nervous system, and overall quality of life. Oral estriol has been associated with similar adverse effects to oral synthetic estrogens with respect to Cardiovascular risks, but there is evidence that transdermal application of estrogens offers a safer alternative that "should be explored". The authors recommend longer term clinical trials of topical estriol to confirm its cardiovascular safety.
Article on Pubmed
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8. - Effects of conventional or lower doses of hormone replacement therapy in postmenopausal women. Koh KK, Shin MS, Sakuma I, Ahn JY, Jin DK, Kim HS, Kim DS, Han SH, Chung W-J, Shin EK.
Arterioscler Thromb Vasc Biol 2004; 24:1516-21.
Progesterone together with lower dose conjugated equine estrogens (CEE) had comparable beneficial effects to conventional high dose CEE on flow mediated dilation, high density lipoproteins, and triglycerides, which may suggest that peripheral vascular function in postmenopausal women is markedly improved by direct actions on the vascular wall.
Article on Pubmed
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9. - Chronic treatment with progesterone but not medroxyprogesterone acetate restores the endothelial control of vascular tone in the mesenteric artery of ovariectomized rats. Chataigneau T, Zerr M, Chataigneau M, Hudlett F, Hirn C, Pernot F, Schini-Kerth VB.
Menopause 2004;11(3):255-63.
This study helps explain the more beneficial effects on the Cardiovascular system of progesterone compared with MPA because of its enhancement of the protective effects of endothelial cells on the arterial walls.
Article on Pubmed
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10. - Prevention of coronary hyperreactivity in pre-atherogenic menopausal rhesus monkeys by transdermal progesterone. Hermsmeyer RK, Mishra RG, Pavcnik D, Uchida B, Axthelm MK, Stanczyk FZ, Burry KA, Illingworth DR, Kaski JC, Nordt FJ.
Arterioscler Thromb Vasc Biol 2004;24(5):955-61.
Previous studies by Hermsmeyer, et al demonstrated a reduction of coronary reactivity in response to sub-physiological levels of progesterone in non-atherogenic monkeys. In this study, the authors sought to determine if transdermal progesterone cream conferred coronary vascular protection in surgically menopausal pre-atherosclerotic rhesus monkeys. Compared with monkeys receiving placebo cream (n= 5), treated monkeys (n= 7) experienced reduced Lipoprotein (a) levels, and an attenuation of coronary vasoconstriction, which was artificially stimulated by intracoronary serotonin plus U46619. Coronary hyperreactivity is a component of coronary artery disease and was demonstrated in this study to be prevented in pre-atherosclerotic primates by progesterone cream treatment.
Article on Pubmed
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11. - Topical progesterone cream does not increase thrombotic and inflammatory factors in postmenopausal women. Stephenson K, Price C, Kurdowska A, Neuenschwander P, Stephenson J, Pinson B, Stephenson D, Alfred D, Krupa A, Mahoney D, Zava D, Bevan M.
Presented at the 46th Annual Meeting of the American Society of Hematology, San Diego, December 4-7, 2004. Blood 2004; 104(11 Pt 1):414b-415b(Abstract 5318).
No change in any of the thrombotic or inflammatory markers studied (total factor VII:C, factor VIIa, factor V, fibrinogen, antithrombin, PAI-1, CRP, TNF?, and IL-6) was observed, despite significant symptomatic improvement compared to placebo, in 30 women receiving 20 mg/day progesterone cream for 4 weeks. This finding indicates a lack of potential adverse effects of progesterone on the Cardiovascular system, particularly with respect to risk of coronary artery disease and stroke. The authors conclude that administration of topical progesterone cream at a daily dose of 20 mg significantly relieves menopausal symptoms in postmenopausal women without adversely altering prothrombotic potential. Since the thrombotic complications that are typically observed with conventional hormone replacement therapy, and have led to an increase in stroke, do not seem to occur with topical progesterone, this treatment should be seriously considered as an effective and safe alternative clinical therapy for women suffering from menopausal symptoms.
Article on Pubmed
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12. - A perspective on HRT for women: picking up the pieces after the Women's Health Initiative trial - Part 2. Gillson GR, Zava DT.
Int J Pharm Compounding 2003;7(5):330-8.
The authors review clinical evidence for the benefits of bioidentical progesterone over synthetic progestins. While both protect the uterine lining from proliferation caused by estrogens, progesterone has beneficial effects on Cardiovascular health. The synergy between progesterone and estradiol , each "turning on" the other's receptors, has the added benefit of allowing the estradiol dosage to be reduced. Oral and transdermal dosing of bioidentical progesterone are discussed.
Link to Abstract
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13. - Part 2 - The science behind bioidentical hormone replacement therapy. Wepfer ST.
Int J Pharm Compounding 2002;6(1):50-54
The author describes the differences between natural progesterone and the synthetic progestin medroxyprogesterone acetate (MPA), saying that the number 1 problem in women's health care today is a lack of understanding about progesterone and a belief that it is the same thing as MPA. The benefits of progesterone on the heart and bone are discussed.
Link to Abstract
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14. - 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. Bagis T, Gokcel A, Zeyneloglu HB, Tarim E, Kilicdag EB, Haydardedeoglu B.
J Clin Endocrinol Metab 2002;87(10):4536-40.
This randomized prospective study evaluated and compared the effects of ten days treatment with oral and vaginal micronized progesterone (MP) and medroxyprogesterone acetate (MPA) on glucose metabolism, lipid profiles, and hormonal parameters in 28 patients with polycystic ovary syndrome (PCOS). Oral MPA and oral MP decreased luteinizing hormone (P = 0.028, P = 0.009, respectively) and total testosterone (P = 0.013, P = 0.037, respectively) levels. There was no change in hormonal parameters with vaginal MP. Basal insulin decreased (P = 0.021) and insulin sensitivity increased significantly in the oral MPA group. Low density lipoprotein cholesterol (LDL) and lipoprotein (a) levels decreased only in the MPA group. This study concluded that MPA and oral MP may reduce insulin sensitivity in patients with PCOS. Vaginal MP had no effect on glucose metabolism and lipid profiles.
Article on Pubmed
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15. - Progesterone, but not medroxyprogesterone, inhibits vascular cell adhesion molecule-1 expression in human vascular endothelial cells. Otsuki M, Saito H, Xu X, Sumitani S, Kouhara H, Kishimoto T, Kasayama S.
Arterioscler Thromb Vasc Biol 2001 Feb;21(2):243-8.
This study utilizing human umbilical vein endothelial cells (HUVEC’s) demonstrated that progesterone, but not medroxyprogesterone acetate (MPA) inhibited expression of vascular cell adhesion molecule-1 (VCAM-1), demonstrating a role for progesterone in the prevention of atherosclerosis. The differing effects of progesterone and MPA are clinically important, as MPA is widely used in hormone replacement therapy, when, as this research suggests, progesterone might be a more appropriate option.
Article on Pubmed
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16. - 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.
J Am Coll Cardiol 2000;36(7):2154-9.
This randomized crossover study compared the effects of estradiol (E2) (2mg/day), estradiol + progesterone (P4) vaginal gel (2 mg/day + 90 mg on alternate days), and estradiol + medroxyprogesterone acetate (MPA) (2 mg/day + 10 mg/day) on exercise-induced myocardial ischemia in eighteen postmenopausal women with coronary artery disease (CAD) or previous myocardial infarction (MI). Utilizing treadmill testing, patients were evaluated for exercise tolerance after each estradiol phase and at day 10 of each progestogen phase. The results demonstrated an increase in exercise tolerance with both E2 alone and E2 + progesterone, but not by E2 + MPA as compared to baseline. Furthermore, E2 + P4 demonstrated a significant increase in exercise tolerance when compared to MPA. The results suggest that progesterone may be preferred to progestins for hormone replacement therapy in women at risk for Cardiovascular disease.
Article on Pubmed
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17. - Preserved forearm endothelial responses with acute exposure to progesterone: A randomized cross-over trial of 17-beta estradiol, progesterone, and 17-beta estradiol with progesterone in healthy menopausal women. Mather KJ, Norman EG, Prior JC, Elliott TG.
J Clin Endocrinol Metab 2000;85(12):4644-9.
Regularly menstruating women enjoy relative protection from Cardiovascular disease. Until recently, this has been attributed to the function of estrogen, despite the fact that progesterone is also present. This study evaluated the differing acute effects of 17-beta estradiol with and without progesterone with progesterone alone on endothelial function in a randomized crossover trial. Endothelial function was evaluated via endothelium dependent and independent forearm blood flow (FBF) using venous occlusion plethysmography. Flow responses were measured during brachial artery infusions achieving physiological levels of E2, E2 + P4, or P4 respectively along with either acetylcholine (an endothelium-dependent vasodilator), or sodium nitroprusside (an endothelium-independent vasodilator) in 27 healthy menopausal women with no cardiovascular disease risk factors. Small, statistically non-significant increases in endothelium-dependent flow responses were seen with all treatments. No impairment in response was seen with P4 alone or in combination with E2. The authors concluded that progesterone does not have detrimental vascular effects in humans.
Article on Pubmed
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18. - Estriol (E3) replacement improves endothelial function and bone mineral density in very elderly women. Hayashi T, Ito I, Kano H, Endo H, Iguchi A.
J Gerontol A Biol Sci Med Sci 2000;55(4):B183-90; discussion B191-3.
The effects of estrogen replacement on blood vessels and bone in very elderly women are not well known because uterine bleeding is a problem when estradiol is given without progesterone. In this study, the weaker estrogen estriol was used because of its known safety when given without progesterone. In 24 women around 80 years old, all of whom were diagnosed with osteoporosis, half received 2 mg/day estriol for 6 months and the other half did not receive estriol. In the estriol treated group, endothelial function (a measure of Cardiovascular health) and bone mineral density significantly improved compared to the control group. The estriol treatment increased both plasma estriol and estradiol levels, but uterine bleeding occurred in only 1 treated woman. The increase in bone resorption may have been due to the increase in plasma estradiol. The authors conclude that estriol is safe and effective for elderly patients.
Article on Pubmed
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19. - Progestins and Cardiovascular risk markers. Sitruk-Ware R.
Steroids 2000; 65(10-11):651-8.
This article reviews the effects of various synthetic progestins and progesterone on Cardiovascular health. Many synthetic progestins, especially 19-nortestosterone and some 17-hyroxyprogesterones, have negative effects on cardiovascular risk factors, whereas natural progesterone does not. Further studies utilizing natural and other steroids should be considered.
Article on Pubmed
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20. - Ovarian steroid protection against coronary artery hyperreactivity in rhesus monkeys. Minshall RD, Stanczyk FZ, Miyagawa K, Uchida B, Axthelm M, Novy M, Hermsmeyer K.
J Clin Endocrinol Metab 1998; 83(2):649-59.
Medroxyprogesterone acetate, but not natural progesterone, negated the protective effects of estradiol against coronary artery hyperreactivity.
Article on Pubmed
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21. - Low-dose progesterone therapy in oestrogenised postmenopausal women: effects on plasma lipids, lipoproteins and liver function parameters. Bolaji II, Grimes H, Mortimer G, Tallon DF, Fottrell PF, O’Dwyer EM.
Eur J Obstet Gynecol Reprod Biol 1993;48(1):61-8.
This 12 month prospective, open, non-comparative study measured the effects progesterone (oral micronized 100mg/day) paired with 0.625 mg conjugated equine estrogens (CEE) and found progesterone had no adverse effects on the lipid profile when combined with CEE. This lack of effect differs from other studies that noted adverse effects on lipid profiles when synthetic progestins were utilized with CEE.
Article on Pubmed
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22. - Menopausal hormone replacement therapy with continuous daily oral micronized estradiol and progesterone. Hargrove JT, Maxson WS, Wentz AC, Burnett LS.
Obstet Gynecol 1989; 73( 4):606-12.
Fifteen menopausal subjects were studied to determine the efficacy and safety of hormone replacement therapy with micronized estradiol (E2) and progesterone. Ten subjects were given 0.7-E2 (1.05 mg daily) and progesterone (200-300 mg daily) and evaluated over one year at month 0, 1, 3, 6 and 12. Five subjects were administered conjugated estrogens (0.625mg daily) and medroxyprogesterone acetate (10 mg daily) and evaluated at the same intervals. Results showed all 10 women on E2 and progesterone had a decrease in total cholesterol with an increase in HDLs and sustained amenorrhea with no endometrial hyperplasia or withdrawal bleeding after six months of observation. Four of five women in the conjugated estrogen group continued to have withdrawal bleeding without endometrial hyperplasia. HDLs also increased in this group but no significant change in total cholesterol was found.
Article on Pubmed
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23. - Natural progesterone and antihypertensive action. Rylance PB, Brincat M, Lafferty K, De Trafford JC, Brincat S, Parsons V, Studd JW.
Br Med J (Clin Res Ed) 1985;290(6461):13-4.
In a placebo controlled, double blind crossover study, increasing doses of natural progesterone was given orally to six men and four postmenopausal women with mild to moderate hypertension who were not receiving any other antihypertensive drugs. Compared to before treatment values and to placebo, progesterone caused a significant reduction in blood pressure, suggesting that progesterone has an antihypertensive action rather than a hypertensive one as has been previously thought. The authors suggest this protective effect of progesterone should be investigated further.
Article on Pubmed
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24. - Subfractions of high-density lipoprotein cholesterol during estrogen replacement therapy: A comparison between progestogens and natural progesterone. Ottosson UB, Johansson BG, von Schoultz B.
Am J Obstet Gynecol 1985;151(6):746-50.
Fifty-eight postmenopausal women were followed with respect to subfractions of high-density lipoprotein during 3 cycles of unopposed estrogen. The women received either levonorgestrel, medroxyprogesterone acetate, or natural progesterone during the last ten days of the treatment period. Both progestogens significantly lowered HDL cholesterol, whereas natural progesterone had no effect on HDL levels.
Article on Pubmed
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