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 research search tool
Categories available are: Androgens; Estrogens; Progesterone; Bone: Brain; Breast; Cardiovascular; Formulations; Menopausal Symptoms; Premenopause; Progestin; Safety; Uterus.
1. - Safety of maternal testosterone therapy during breast feeding. Glaser RL, Newman M, Parsons M, Zava D, Glaser-Garbrick D.
Int J Pharm Compounding 2009;13(4):314-317.
This was a study of testosterone levels in maternal blood, the infant's blood, and breast milk, after a nursing mother was given testosterone in the form of sublingual drops, vaginal cream, and a pellet implant. None of the delivery methods resulted in a significant increase of testosterone in breast milk or the infant's blood, although levels were raised in the maternal blood showing that the testosterone was absorbed after all 3 delivery methods. The testosterone therapy was effective in relieving symptoms of testosterone deficiency in the mother and was safe for the breast-fed infant.
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2. - The physiologic role and use of estriol. Paoletti J.
Int J Pharm Compounding 2009;13(4)270-275.
Estriol has an important physiological role in the prevention of breast cancer by balancing the effects of the stronger estrogens, estradiol and estrone, effectively acting as an anti-estrogen. The author explains this phenomenon and explains a rationale for appropriate dosing of estriol relative to estradiol in bioidentical hormone replacement therapy.
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3. - 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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4. - Testosterone for low libido in postmenopausal women not using systemic oestrogen therapy. Davis SR.
Med J Aust. 2009; 191(3):134-5.
This editorial, written by the principal investigator for the "Aphrodite" study, concludes that the use of transdermal testosterone for hypoactive sexual desire disorder (HSDD) shows promising results but long-term Safety requires further study. The article describes the Aphrodite study, in which 814 women with HSDD were randomized to receive a patch delivering 150 or 300 mcg/day testosterone, or placebo patches, for 52 weeks. The testosterone groups reported significantly more satisfying sexual events and reduction of distress, although the frequency of sexual activity did not increase. Benefits were seen after 8 weeks of therapy. No significant adverse effects were seen.
Article on Pubmed
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5. - 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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6. - The role of testosterone in the management of hypoactive sexual desire disorder in postmenopausal women. Krapf JM, Simon JA.
Maturitas. 2009; 63(3):213-9.
This article reviews testosterone's role in sexual function in women. Research is going on to study the Safety and effectiveness of transdermal testosterone therapy in women with low sexual desire, sometimes called HSDD (hypoactive sexual desire disorder) if it leads to distress. The prevalence of this disorder is highest in women who are surgically menopausal, i.e., they have had both ovaries removed, which results in a sudden decline in testosterone levels that leads to a reduced desire for sex and less satisfying sex. The authors review clinical studies of transdermal testosterone therapy, both with and without estrogen, concluding that it is safe and effective in women struggling with HSDD.
Article on Pubmed
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7. - Hormone therapy - it's time for a second opinion. Collins JJ, Ahlgrimm M.
Int J Pharm Compounding 2008;12(7):123-127.
This paper highlights some counterarguments to an opinion piece by the American College of Obstetrics and Gynecologists, which has been widely quoted as evidence against the use of bioidentical hormones. The authors urge clinicians reading the ACOG opinion piece to ask themselves whether it really reflects clinical advances in the use of compounded and FDA-approved bioidentical hormones that have transformed the practice of hormone replacement therapy. They recommend that people read the original research, rather than quoting reviews and opinions that are not well founded in the literature.
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8. - 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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9. - 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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10. - Could transdermal estradiol + progesterone be a safer postmenopausal HRT? A review. L'Hermite M, Simoncini T, Fuller S, Genazzani AR.
Maturitas 2008;60(3-4):185-201.
This detailed review examines the way different types of hormone replacement therapy (HRT) affect the cardiovascular system, the brain, and the risk of breast cancer. It discusses the research that shows that non-oral estrogens have more favorable cardiovascular effects, such as improved blood pressure control and lower risk of thrombosis. It discusses the benefits of using natural progesterone rather than synthetic progestins in association with estrogens in HRT. Natural progesterone has a beneficial effect on blood vessels and the brain, and confers less or even no risk of breast cancer, compared with synthetic progestins.
Article on Pubmed
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11. - Hormones in wellness and disease prevention: common practices, current state of the evidence, and questions for the future. Schwartz ET, Holtorf K.
Prim Care 2008;35(4):669-705.
This review examines the role of hormones as critical components of overall wellness, and therefore the potential for disease prevention of ensuring that hormone levels are optimal. The authors outline age-related hormone deficiencies and supplementation strategies. The review covers estrogens, progesterone, testosterone, growth hormone and thyroid hormones, covering not only the effects of deficiency and the risk/benefit of supplementation, but also controversies surrounding such treatment. The diagnosis of hormone deficiency and monitoring of treatment is also discussed.
Article on Pubmed
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12. - Correcting misconceptions about compounding bioidentical hormones: a review of the literature. Paoletti J.
Int J Pharm Compounding 2007;11(4):269-272.
The author proposes that any physician prescribing compounded bioidentical hormones should be aware of current information published in the scientific literature. There is much published evidence for the Safety of bioidentical progesterone and estrogens, compared to their synthetic alternatives. Unfortunately, some expert advisory groups ignore the published evidence and state opinion rather than fact.
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13. - 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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14. - A comprehensive review of the Safety and efficacy of bioidentical hormones for the management of menopause and related health risks. Moskowitz D.
Altern Med Rev. 2006 Sep;11(3):208-23.
This review describes the various synthetic estrogens and progestins used in hormone replacement therapy and discusses their Safety in relation to natural alternatives. Natural estrogens and progesterone are being increasingly used in clinical practice and have demonstrated effectiveness in treating menopausal symptoms. They also have improved safety profiles with respect to breast cancer risk and cardiovascular effects.
Article on Pubmed
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15. - Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort. Fournier A, Berrino F, Riboli E, Avenel V, Clavel-Chapelon F.
Int J Cancer 2005; 114(3):448-54.
Combined HRT with estrogen (either oral or transdermal) and synthetic progestins was found to carry a significantly increased risk of breast cancer compared with estrogens plus oral micronized progesterone. In fact, no increase in breast cancer risk was seen in the estrogen plus oral micronized progesterone group compared with estrogen alone. This large multicenter study therefore suggests that there is a dramatic difference between the effects of bioidentical progesterone versus synthetic progestins on breast cancer risk.
Article on Pubmed
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16. - Progestins and progesterone in hormone replacement therapy and the risk of breast cancer. Campagnoli C, Clavel-Chapelon F, Kaaks R, Peris C, Berrino F.
J Steroid Biochem Mol Biol 2005; 96(2):95-108.
The authors discuss the non-progesterone-like effects of synthetic progestins, which can contribute to the increased risk of breast cancer when these are used as part of a combined hormone therapy regimen. In contrast, bioidentical progesterone does not increase the risk of breast cancer, consistent with experimental in vivo data that shows progesterone has no adverse effect on breast tissue.
Article on Pubmed
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17. - 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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18. - 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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19. - Part 3 - The science behind bioidentical hormone replacement therapy. Wepfer ST.
Int J Pharm Compounding 2002;6(2):142-6
Differences between synthetic progestins and bioidentical progesterone in terms of their effects on breast cancer risk, estrogen dominance, and vasomotor symptoms are discussed. The review also covers the use of testosterone for postmenopausal women who have androgen deficiency because of surgically induced menopause. Androgen deficiency is also seen in women receiving estrogen replacement therapy, which reduces bioavailable testosterone because it increases levels of sex hormone binding globulin in the blood. The author concludes that bioidentical hormones are more effective and safer than the synthetic alternatives, but hopes that large trials will soon be conducted to confirm their promising effects.
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20. - 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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21. - Progestogens in hormonal replacement therapy: new molecules, risks, and benefits. Sitruk-Ware R.
Menopause 2002;9(1):6-15.
The classifications of various progestogens (natural and synthetic) are reviewed in terms of their risks and benefits. This review clearly elucidates the differences in the mode of action of various synthetic progestins as well as progesterone.
Article on Pubmed
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22. - Comparison of physical and emotional side effects of progesterone or medroxyprogesterone in early postmenopausal women. Cummings JA, Brizendine L.
Menopause 2002;9(4):253-63.
Twenty-three early postmenopausal women were randomized to either medroxyprogesterone acetate (MPA) or oral micronized progesterone combined with conjugated equine estrogens (CEE) and followed for 91 days in a sequence of treatments. None of the hormone treatments had any noticeable effect on mood. Participants using MPA experienced more breast tenderness and bleeding than those using progesterone. This study debunks the belief that progesterone depresses mood in healthy individuals.
Article on Pubmed
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23. - Safety of estrogen/androgen regimens. Simon JA.
J Reprod Med 2001;46(3 Suppl):281-90.
Article on Pubmed
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24. - Natural vaginal progesterone is associated with minimal psychological side effects: a preliminary study. Shantha S, Brooks-Gunn J, Locke RJ, Warren MP.
J Womens Health Gend Based Med 2001;10(10):991-7.
This 3 month, multicenter randomized study evaluated the psychological side effects of a vaginally applied progesterone gel in reproductive aged women treated for hypothalamic amenorrhea or premature ovarian failure. No differences were noted in psychometric measures as evaluated by the Hopkins Symptom Checklist. Natural progesterone in a vaginal gel can be an effective treatment for women requiring hormone therapy.
Article on Pubmed
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25. - Progesterone and progestins: applications in gynecology. de Ziegler D, Fanchin R.
Steroids 2000;65(10-11):671-9.
This paper reviews the use of a transvaginal progesterone gel as a viable option to other routes of application of natural progesterone (intramuscular, oral micronized), and offered it as a viable option to synthetic progestins given the low incidence of side effects noted in existing studies.
Article on Pubmed
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26. - Safety and efficacy of oestriol for symptoms of natural or surgically induced menopause. Takahashi K, Okada M, Ozaki T, Kurioka H, Manabe A, Kanasaki H, Miyazaki K.
Hum Reprod 2000;15(5):1028-36.
The authors gave 2 mg/day oral estriol for one year to 53 postmenopausal women (aged 40-62). None of the patients stopped treatment due to side effects; level of satisfaction with the treatment increased throughout the study, and averaged at 85% in naturally menopausal women and 93% in surgically menopausal women by the end of the year. Menopausal symptoms were significantly reduced. No distinctive effects on bone or lipid levels were seen. The authors suggest that estriol is a good choice of HRT to reduce symptoms in women who are not susceptible to osteoporosis or coronary artery disease.
Article on Pubmed
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27. - Progestogens used in menopause. Side effects, mood and quality of life. Sherwin BB.
J Reprod Med 1999;44(2 Suppl):227-32.
This review summarizes the effects of progesterone on mood and other brain functions. Progesterone receptors are present in many of the same areas of the brain as estrogen receptors, including the limbic system and hypothalamus. The limbic system plays a prominent role in regulating mood and emotion. As a comparison, progesterone decreases brain excitability, while estrogens increase it. This relates to why women with epilepsy have a higher frequency of seizures during the part of the cycle when estrogen levels are high, and a reduced frequency when progesterone levels are high. Estrogen and progesterone may also have differing effects on MAO, thereby affecting concentration of serotonin (a mood elevator) in the brain.
Article on Pubmed
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28. - Percutaneous progesterone use and risk of breast cancer: results from a French cohort study of premenopausal women with benign breast disease. Plu-Bureau G, Le MG, Thalabard JC, Sitruk-Ware R, Mauvais-Jarvis P.
Cancer Detect Prev 1999;23(4):290-6.
This cohort study followed 1150 premenopausal French women diagnosed with benign breast disease. Topical progesterone cream, a common treatment for mastalgia in Europe, had been prescribed to 58% of the women. Follow-up accumulated 12,462 person-years. There was no association noted between progesterone cream use and breast cancer risk. Furthermore, women who had used both progesterone cream and an oral progestogen had a significant decrease in breast cancer risk (RR= 0.5) as compared to women who did not use progesterone cream. There was no significant difference in the risk of breast cancer in percutaneous progesterone users versus nonusers among oral progestogen users. These results suggest there are no deleterious effects caused by percutaneous progesterone use in women with benign breast disease.
Article on Pubmed
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29. - Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial. Scarabin PY, Alhenc-Gelas M, Plu-Bureau G, Taisne P, Agher R, Aiach M.
Arterioscler Thromb Vasc Biol 1997; 17(11): 3071-8.
Oral hormone replacement therapy postmenopausally has been associated with an increased risk of stoke due to thromboembolism. This randomized, placebo-controlled study evaluated the differing effects of oral and transdermal estrogen/progesterone therapy or placebo on hemostasis. Oral, but not transdermal therapy was seen to increase the susceptibility of clotting in healthy post-menopausal women 45-64 years. The authors concluded that route of administration of hormones can affect the incidence of clotting, with oral hormone replacement increasing risk, and transdermal hormone replacement demonstrating no negative effect on clotting.
Article on Pubmed
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