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Categories available are: Androgens; Estrogens; Progesterone; Bone: Brain; Breast; Cardiovascular; Formulations; Menopausal Symptoms; Premenopause; Progestin; Safety; Uterus.
1. - 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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2. - 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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3. - 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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4. - 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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5. - 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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6. - 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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7. - Estriol: women's choice vs. a manufacturer's greed. Goodrum J.
Int J Pharm Compounding 2008;12(4):286-292.
This is a response to the FDA's attempt to halt the compounding of hormone preparations containing estriol. The author explains the background to this, which was primarily instigated by the pharmaceutical company Wyeth (manufacturer of Prempro). Estriol has been used clinically for decades without adverse effects when dosed appropriately, and is widely available in Europe. An explanation of actions being taken by the International Association of Compounding Pharmacists to reverse the FDA's ban is given.
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8. - 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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9. - Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Fournier A, Berrino F, Clavel-Chapelon F.
Breast Cancer Res Treat 2008;107(1):103-11.
This large multicenter study in France followed 80,377 postmenopausal women for up to 12 years, and looked in particular at whether the type of progestogen used in combination with estrogen made a difference to the risk of developing breast cancer in those women who used hormone replacement therapy (HRT). The estrogen in HRT is primarily transdermal estradiol in France. Compared with those women who did not use HRT at all, women using estrogen alone had a 1.29-fold increased risk of developing breast cancer; women using estrogen plus natural progesterone had the same risk as women using no HRT. In women using synthetic progestins in combination with estrogen, the particular progestin used made a difference to breast cancer risk; women using dydrogesterone had a 1.16-fold increased risk of breast cancer, but those using other progestins had a 1.69-fold increased risk of breast cancer, compared to women not using HRT. The authors note that dydrogesterone is the progestin most similar to natural progesterone in its chemical structure and pharmacological effects.
Article on Pubmed
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10. - 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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11. - 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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12. - 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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13. - Hormone replacement therapy and the cardiovascular system: lessons learned and unanswered questions. Ouyang P, Michos ED, Karas RH.
J Am Coll Cardiol 2006; 47(9):1741-53.
This review discusses the lack of benefit of estrogen therapy in older women for the prevention of cardiovascular problems.
Article on Pubmed
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14. - Differential effects of oral conjugated equine estrogen and transdermal estrogen on atherosclerotic vascular disease risk markers and endothelial function in healthy postmenopausal women. Ho JY, Chen MJ, Sheu WH, Yi YC, Tsai AC, Guu HF, Ho ES.
Hum Reprod 2006; 21(10):2715-20.
In this comparison of 0.625 mg/day oral conjugated equine estrogen (CEE) versus 0.6 mg/day 17?-estradiol transdermal gel for 6 months or no treatment, the oral CEE group showed significantly increased levels of C-reactive protein (CRP), a marker of inflammation, while the transdermal and control groups showed no increase in CRP. The transdermal estradiol group showed a similar beneficial effect on flow-mediated vasodilation in the brachial artery to the CEE group, indicating a comparative therapeutic benefit but without increasing the risk of atherosclerosis.
Article on Pubmed
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15. - The rise and fall of menopausal hormone therapy. Barrett-Connor E, Grady D, Stefanik ML.
Annu Rev Public Health 2005; 26:115-40.
This important review by leading epidemiologists looks at the results of major clinical trials of hormone therapy and suggests that any long term benefits of estrogen therapy for the prevention of fractures could be achieved with much lower doses of estrogen.
Article on Pubmed
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16. - Bio-identical steroid hormone replacement: selected observations from 23 years of clinical and laboratory practice. Wright JV.
Ann N Y Acad Sci. 2005;1057:506-24.
This review discusses the types of Estrogens used in bioidentical hormone replacement, including their dosages and routes of administration. The author advocates the use of natural hormones because of the problems with using non-human identical synthetic hormones, highlighted largely by the Women's Health Initiative trial. However, bioidentical estrogens must be properly monitored to ensure appropriate dosing, just as is common for thyroid hormone replacement. The metabolism of estradiol to estrone and estriol is discussed. The author advocates the use of iodine supplements, which stimulate the metabolism of estradiol towards estriol. The amount of circulating estriol relative to estradiol and estrone is important in breast cancer risk: the greater the relative amount of estriol, the lower the breast cancer risk.
Article on Pubmed
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17. - Hormone replacement with estradiol: conventional oral doses result in excessive exposure to estrone. Friel PN, Hinchcliffe C, Wright JV.
Altern Med Rev 2005;10(1):36-41.
Studies have shown increased breast cancer risk in women with high levels of estradiol and estrone in their urine. This study therefore investigated urinary estrone and estradiol concentrations in 35 women taking between 0.025 and 2.0 mg/day oral estradiol. Urinary levels of both Estrogens increased as the estradiol dosage increased. At doses of 0.25 mg/day or higher, urine estrone levels were higher than seen in non-pregnant premenopausal women, while at doses of 0.5 mg/day or higher, urine estradiol was higher than in non-pregnant premenopausal women. Estradiol given at a dose of 1 mg/day resulted in excessive serum estrone levels. To minimize breast cancer risk, the authors recommend oral estradiol doses no higher than 0.25 mg/day.
Article on Pubmed
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18. - Double blind, randomized study of estradiol replacement therapy on markers of inflammation, coagulation and fibrinolysis. Zegura B, Keber I, Sebestjen M, Koenig W.
Atherosclerosis 2003;168(1):123-9.
Article on Pubmed
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19. - [Comparison of changes in biochemical markers of bone turnover after 6 months of hormone replacement therapy with either transdermal 17 beta-estradiol or conjugated equine estrogen plus nomegestrol acetate.] Collette J, Viethel P, Dethor M, Chevallier T, Micheletti MC, Foidart JM, Reginster JY.
Gynecol Obstet Fertil 2003;31(5):434-41.
Article on Pubmed
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20. - Pharmacokinetics of estradiol, progesterone, testosterone and dehydroepiandrosterone after transbuccal administration to postmenopausal women. Wren BG, Day RO, McLachlan AJ, Williams KM.
Climacteric 2003;6(2):104-11.
Article on Pubmed
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21. - Efficacy, safety and acceptability of a seven-day, transdermal estradiol patch for estrogen replacement therapy. Jarupanich T, Lamlertkittikul S, Chandeying V.
J Med Assoc Thai 2003;86(9):836-45.
Article on Pubmed
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22. - Ultralow-dose micronized 17ß-estradiol and bone density and bone metabolism in older women: a randomized controlled trial. Prestwood KM, Kenny AM, Kleppinger A, Kulldorff M.
JAMA 2003; 290(8):1042-8.
This study of 0.25 mg/day oral estradiol versus placebo for 3 years in women over 65 years old (with 100 mg/day oral micronized progesterone in women with a uterus in both groups) found an increase in bone density in the estradiol group compared with placebo.
Article on Pubmed
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23. - A perspective on HRT for women: picking up the pieces after the Women's Health Initiative trial - Part 1. Gillson GR, Zava DT.
Int J Pharm Compounding 2003;7(4):250-6.
This article discusses some fundamental aspects of safer hormone replacement therapy that may have been overlooked in the debate surrounding bioidentical versus synthetic hormones: Oral delivery of hormones is not optimal; application of hormones to the skin (transdermal application) has many important advantages; and synthetic progestins are not acceptable as a substitute for natural progesterone. The evidence for and principles behind these factors are presented.
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24. - Orally and transdermally replaced estradiol improves endothelial function equally in middle-aged women after surgical menopause. Zegura B, Keber I, Sebestjen M, Borko E.
Am J Obstet Gynecol 2003;188(5):1291-6.
Forty-three surgically induced (6 weeks postop) menopausal women were randomly assigned in a double-blind study to 28 weeks of 2.0mg oral or 50mg transdermal estradiol. Looking at blood flow through the brachial artery, flow-mediated dilation (ultrasound) in the oral group increased 6.0 to 13.2% and in the transdermal group increased 7.0 to 14.9% Results indicate that both oral and transdermal administration had equal effect on arterial endothelium independent of lipid profiles and increased vasodilation.
Article on Pubmed
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25. - Short-term use of estradiol for depression in perimenopausal and postmenopausal women: a preliminary report. Cohen LS, Soares CN, Poitras JR, Prouty J, Alexander AB, Shifren JL.
Am J Psychiatry 2003;160(8):1519-22.
Twenty-two peri- or post-menopausal women with median age of 50 years experiencing moderate severity depression (DSM-IV major depression, minor depression, or dysthymia) were enrolled in a 4 week open-label clinical trial of 100 micrograms of transdermal 17B estradiol. Results showed decreased score on Montgomery-Asberg Depression Rating Scale (20 to 11.50) and Beck Depression Inventory. Greene-Climacteric Scale scores showed measured improvement during the 4 week study. Changes in depression scales and climacteric scales were not significantly correlated. Perimenopausal (6) women showed greater improvement in depression scales than postmenopausal women (2). Authors suggested this study supports previous results showing that the effect of estrogen therapy on mood may be independent of antidepressant effects mediated by alleviation of vasomotor symptoms and that estrogen therapy may be of benefit to perimenopausal women experiencing moderately severe depression.
Article on Pubmed
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26. - Percutaneous 17beta-estradiol gel for the treatment of vasomotor symptoms in postmenopausal women. Archer DF, Estrogel Study Group
Menopause. 2003; 10(6):516-21.
The frequency of moderate-to-severe hot flashes was significantly reduced after once daily application of estradiol gel for 12 weeks, compared to placebo gel, in 221 postmenopausal women. Two doses of estradiol gel were used: 1.25 g, containing 0.75 mg estradiol, and 2.5 g, containing 1.5 mg estradiol. Both were effective and well tolerated, although the higher dose resulted in more estrogen-related adverse events.
Article on Pubmed
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27. - Effects of transdermal estradiol delivered by a matrix patch on bone density in hysterectomized, postmenopausal women: a 2-year placebo-controlled trial. Arrenbrecht S, Boermans AJ.
Osteoporos Int 2002;13(2):176-83.
Article on Pubmed
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28. - The effects of oral estriol on the endometrium in postmenopausal women. Granberg S, Eurenius K, Lindgren R, Wilhelmsson L.
Maturitas 2002;42(2):149-56.
This study conducted endometrial evaluation using both transvaginal ultrasound (TVS) and histologic biopsy by Pipelle in postmenopausal women taking a low-dose oral estriol (1 or 2 mg daily) for a mean duration of 4.3 years. Mean endothelial thickness in the study group after one year was 3.0mm and in the control group was 2.4mm. There was a noted increase in atrophic vaginal epithelium in the control group. There was a noted increased incidence of endometrial polyps in the study group (14.1%) compared to the control group (2.9%) although this was not determined to be clinically significant.
Article on Pubmed
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29. - Twice-weekly transdermal estradiol and vaginal progesterone as continuous combined hormone replacement therapy in postmenopausal women: a 1-year prospective study. Cicinelli E, de Ziegler D, Galantino P, Pinto V, Barba B, Morgese S, Schonauer S.
Am J Obstet Gynecol 2002;187(3):556-60.
In this study of 35 postmenopausal women, twice-weekly administration of a progesterone vaginal gel (45 mg P4/day) sufficiently protected the endometrium in women receiving transdermal estradiol (0.05 mg/d) as revealed by endometrial thickness and histology. The authors present vaginally applied progesterone as a viable option for hormone replacement therapy at menopause.
Article on Pubmed
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30. - Part 1 - The science behind bioidentical hormone replacement therapy. Wepfer ST.
Int J Pharm Compounding 2001;5(6):10-12
The author defines bioidentical hormone therapy and reviews the scientific literature supporting its use to treat menopausal symptoms, focusing on the 3 Estrogens: estrone, estradiol, and estriol, as well as progesterone and testosterone.
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31. - Effect of oral estriol on urogenital symptoms, vaginal cytology, and plasma hormone level in postmenopausal women. Manonai J, Theppisai U.
J Med Assoc Thai 2001;84(4):539-44.
Article on Pubmed
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32. - The effects of transdermal estradiol in combination with oral norethisterone on lipoproteins, coagulation, and endothelial markers in postmenopausal women with Type 2 diabetes: a randomized, placebo-controlled study. Perera M, Sattar N, Petrie JR, Hillier C, Small M, Connell JM, Lowe GD, Lumsden MA.
J Clin Endocrinol Metab 2001;86(3):1140-3.
This study showed that transdermal estradiol and oral norethisterone reduce plasma triglyceride and total cholesterol levels, factor VII activity and von Willebrand factor antigen levels in women with Type 2 diabetes without a concurrent change in adiposity or glycemic control. The authors suggest that this protocol might be of benefit for women at high risk of cardiovascular disease.
Article on Pubmed
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33. - Short term oral estriol treatment restores normal premenopausal vaginal flora to elderly women. Yoshimura T, Okamura H.
Maturitas 2001;39(3):253-7.
This study looked at short term (14 days) oral estriol (2.0mg/day) treatment for atrophic vaginitis in 59 postmenopausal women aged 50-75 years. The results showed that in the majority of women in the study group the oral estriol restored normal vaginal flora by the end of the treatment period.
Article on Pubmed
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34. - Efficacy and safety of oral estriol for managing postmenopausal symptoms. Takahashi K, Manabe A, Okada M, Kurioka H, Kanasaki H, Miyazaki K.
Maturitas 2000;34(2):169-77.
Article on Pubmed
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35. - Pharmacodynamics of oEstrogens and progestogens. de Lignieres B, Silberstein S.
Cephalalgia 2000;20(3):200-7.
Article on Pubmed
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36. - Oestradiol-releasing vaginal ring versus oestriol vaginal pessaries in the treatment of bothersome lower urinary tract symptoms. Lose G, Englev E.
BJOG 2000;107(8):1029-34.
Article on Pubmed
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37. - Sublingual administration of micronized estradiol and progesterone, with and without micronized testosterone: effect on biochemical markers of bone metabolism and bone mineral density. Miller BE, De Souza MJ, Slade K, Luciano AA.
Menopause 2000;7(5):318-26.
Article on Pubmed
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38. - 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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39. - Comparison of the long-term effects of oral estriol with the effects of conjugated estrogen on serum lipid profile in early menopausal women. Itoi H, Minakami H, Iwasaki R, Sato I.
Maturitas 2000;36(3):217-22.
This was a randomized comparison study with three arms: 2.0mg estriol + 2.5mg medroxyprogesterone (E3), 0.625mg conjugated estrogen + 2.5mg medroxyprogesterone (CE) and a vitamin D and Calcium combination (control), looking at changes in serum lipid profiles in early menopausal women. The sample size was 67 women. After 48 months on the randomized protocol, the serum lipid profiles showed that those in the E3 group decreased total cholesterol and triglycerides (-4.9 and – 6.7) compared to the control of (+5.4 and +6.1) and CE group of (-1.9 and +17.6). The E3 group showed less significant changes in HDL cholesterol and LDL cholesterol when compared to the CE protocol: E3 (+3.8 and -5.2), CE (+10.7 and -11.4), control (-3.6 and +11.8). The results show the improvement of serum lipid profiles in response to estrogen. The authors suggested that in women where bleeding has been a problem response to certain estrogen protocols, the low-dose estriol may be an alternative treatment for those at risk of cardiovascular disease.
Article on Pubmed
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40. - Antiinflammatory effects of estrogen on microglial activation. Bruce-Keller AJ, Keeling JL, Keller JN, Huang FF, Camondola S, Mattson MP.
Endocrinology 2000;141(10):3646-56.
This study identified new pathways for the estrogenic anti-inflammatory effects on brain function, potentially leading to identification of new methods for improving neurodegenerative disease, specifically involving the microglial cells.
Article on Pubmed
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41. - Effects of estradiol with and without testosterone on body composition and relationships with lipids in postmenopausal women. Davis SR, Walker KZ, Strauss BJ.
Menopause 2000;7(6):395-401.
Article on Pubmed
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42. - The effect of low dose micronized 17beta-estradiol on bone turnover, sex hormone levels, and side effects in older women: a randomized, double blind, placebo-controlled study. Prestwood KM, Kenny AM, Unson C, Kulldorff M.
J Clin Endocrinol Metab 2000;85(12):4462-9.
This study determined that oral low-dose estrogen (0.25mg/day) had similar beneficial effects on bone health in elderly (mean age 75 years) postmenopausal women without the breast tenderness and bleeding associated with higher doses. Authors recommended the use of serum E2 levels as the guide for therapeutic effect at a range of 10-28 pg/L.
Article on Pubmed
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43. - 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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44. - Estriol: safety and efficacy. Head KA.
Altern Med Rev 1998;3(2):101-13.
The author reviews research on estriol, particularly looking at its effectiveness in treating menopausal symptoms, and in protecting against osteoporosis and cardiovascular disease. Estriol is a weaker estrogen than estradiol or estrone, and has been found to be effective in controlling symmptoms such as hot flashes, insomnia, vaginal dryness, and frequent urinary tract infections. Estriol was not shown to effectively prevent bone loss except in some Japanese studies, and the author speculates that the Japanese diet with its phytoestrogen content may have been a factor. Estriol's protective effect against cardiovascular disease has not been well studied.
Article on Pubmed
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45. - Percutaneous estradiol gel with an intrauterine levonorgestrel releasing device or natural progesterone in hormone replacement therapy. Suvanto-Luukkonen E, Sundstrom H, Penttinen J, Laara E, Pramila S, Kauppila A.
Maturitas 1997;26(3):211-7.
Article on Pubmed
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46. - Physiologic estradiol replacement therapy and cardiac structure and function in normal postmenopausal women: a randomized, double-blind, placebo-controlled, crossover trial. Snabes MC, Payne JP, Kopelen HA, Dunn JK, Young RL, Zoghbi WA.
Obstet Gynecol 1997;89(3):332-9.
In a randomized, double-blind, placebo-controlled, crossover clinical trial of 31 postmenopausal women, average age 59.7 years, using 2.0 mg of oral estradiol (E2) daily, the authors investigated the effects of estradiol on cardiac function and structure. This study did not include the use of progestins with estrogen. 12 weeks of E2 therapy showed no change in left ventricular thickness or mass, left atrial size or aortic size. There was a small but significant increase in left ventricular end-diastolic volume but it was not associated with change in end-systolic volume or ejection fraction changes. Heart rate and systolic and diastolic pressures were unchanged after 3 months of treatment. Time-velocity integral of flow and peak flow velocities were unaffected by E2 treatment. Authors concluded that estrogen replacement therapy did not affect cardiac structure or size in normal postmenopausal women (after 12 weeks of treatment).
Article on Pubmed
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47. - 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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48. - Low and conventional dose transdermal oestradiol are equally effective at preventing bone loss in spine and femur at all post-menopausal ages. Evans SF, Davie MW.
Clin Endocrinol (Oxf) 1996;44(1):79-84.
Article on Pubmed
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49. - [Usefulness of estriol for the treatment of bone loss in postmenopausal women] Nozaki M, Hashimoto K, Inoue Y, Sano M, Nakano H.
Nippon Sanka Fujinka Gakkai Zasshi 1996;48(2):83-8.
Article on Pubmed
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50. - Transdermal estrogen replacement therapy: beneficial effects on hemostatic risk factors for cardiovascular disease. Lindoff C, Peterson F, Lecander I, Martinsson G, Astedt B.
Maturitas 1996;24(1-2):43-50.
Article on Pubmed
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51. - Effect of oral estradiol on Lp(a) and other lipoproteins in postmenopausal women. A randomized, double-blind, placebo-controlled, crossover study. Haines C, Chung T, Chang A, Masarei J, Tomlinson B, Wong E.
Arch Intern Med 1996;156(8):866-72.
In a randomized, double-blind, placebo-controlled, crossover study, 91 surgically postmenopausal women received either 6 months of 2mg daily oral estradiol followed by 6 months of placebo or the opposite regimen. During treatment phase, Group One showed decreased Lipoprotein (a) concentration (10.78 to 6.44 mg/dL) and LDL-C with increase in HDL-C and TG while Group Two showed a less pronounced decrease (12.74 to 10.75). 53 women continued oral estrogen therapy for an additional 12 months. Lipoprotein (a) levels were essentially unchanged from previous measures at the end of the treatment phase after 12 months of additional therapy. Authors suggested that reduced Lipoprotein (a) levels with extended oral estrogen therapy support a cardioprotective effect of HRT in postmenopausal women.
Article on Pubmed
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52. - Efficacy and safety of estriol replacement therapy for climacteric women. Yang TS, Tsan SH, Chang SP, Ng HT.
Zhonghua Yi Xue Za Zhi (Taipei) 1995;55(5):386-91.
Article on Pubmed
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53. - Vascular responses to 17 beta-oestradiol in postmenopausal women. Riedel M, Oeltermann A, Mugge A, Creutzig A, Rafflenbeul W, Lichtlen P.
Eur J Clin Invest 1995;25(1):44-7.
Article on Pubmed
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54. - [Treatment of climacteric urogenital disorders with an estriol-containing ointment] Koloszar S, Kovacs L.
Orv Hetil 1995;136(7):343-5.
Article on Pubmed
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55. - An alternative method of hormone replacement therapy using the natural sex steroids. Hargrove JT, Osteen KG.
Menopause 1995;6(4):653-674
The authors present a protocol for hormone replacement therapy in postmenopausal women with low levels of estradiol, testosterone, and DHEA. They advocate individualizing therapy for each woman according to her needs, and monitoring blood levels closely. All postmenopausal women are deficient in progesterone, so this should also be given unless contraindicated. Hormones should be replaced only up to the levels found in premenopausal women. Natural hormones are preferable to their synthetic counterparts.
Not available on Pubmed
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56. - When applied to facial skin, does estrogen ointment have systemic effects? Kainz C, Gitsch G, Stani J, Breitenecker G, Binder M, Schmidt JB.
Arch Gynecol Obstet 1993;253(2):71-4.
Article on Pubmed
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57. - A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. Raz R, Stamm WE.
N Engl J Med 1993;329(11):753-6.
This randomized, double blind, placebo-controlled trial looked at the incidence of urinary tract infections (UTI) in 93 postmenopausal women using 0.5 mg estriol vaginal cream once nightly for two weeks followed by twice weekly application or placebo. Results showed significantly lower UTI rates in treatment group (0.5 infections per patient-year vs. 5.9 for placebo group). The mean vaginal pH fell from 5.5+-0.7 to 3.6+-1.0 for treatment group and 5.8+-1/2 to 6.1+-2.0 in placebo group and there was an increase in vaginal colonization with lactobacilli in the treatment group. Authors recommend use of topical vaginal estriol in preventive treatment of women with frequent UTI as possible replacement for long-term use of nitrofurantoin, co-trioxazole, trimethoprim, cehpalexin or fluoroquinolones.
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58. - Liver metabolism during treatment with estradiol and natural progesterone. Darj E, Axelsson O, Carlstrom K, Nilsson S, von Schoultz B.
Gynecol Endocrinol 1993;7(2):111-4.
Article on Pubmed
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59. - Effects of protracted administration of estriol on the lower genitourinary tract in postmenopausal women. Iosif CS.
Arch Gynecol Obstet 1992;251(3):115-20.
Article on Pubmed
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60. - Low-dosage micronized 17 beta-estradiol prevents bone loss in postmenopausal women. Ettinger B, Genant HK, Steiger P, Madvig P.
Am J Obstet Gynecol 1992;166(2):479-88.
The authors evaluated the effects of 17 beta-estradiol (E2) in a randomized, double-blind, dose ranging study of 41 postmenopausal women conducted in 2 phases. Phase one included phased E2 doses (0.5mg, 1.0mg, 2.0mg) plus calcium supplementation (to serum value of 1500mg). Phase two included E2 doses plus random cessation of calcium supplementation. Progestins were added during phase two (total study time of 18 months). Results showed very little change in bone density results for placebo group (0.5 – 0.9%) whereas treatment group showed significant increases from baseline bone density. In phase two the treatment groups showed an annual change in bone density of 2.0%. There was a positive correlation between total calcium intake and the change in bone density results. The study showed a continuous dose-response effect on bone density results. Authors concluded that low dose (1.0mg) beta-estradiol and 1000mg of calcium prevented bone loss in postmenopausal women.
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61. - Biologic effects of transdermal estradiol. Chetkowski RJ, Meldrum DR, Steingold KA, Randle D, Lu JK, Eggena P, Hershman JM, Alkjaersig NK, Fletcher AP, Judd HL.
N Engl J Med 1986 Jun 19;314(25):1615-20.
Twenty-three postmenopausal women were randomly assigned to use of transdermal estradiol in four increasing doses (25, 50, 100, 100 micrograms per 24 hours) followed by daily oral dose of conjugated equine Estrogens in two doses (0.625 mg, 1.25 mg) or to use of oral conjugated equine estrogens followed by transdermal estradiol. Results showed a dose-response relationship between the amount of estradiol delivered and the serum measure of the hormone. Estrone concentrations also rose with transdermal application. At the 50 and 100 microgram transdermal dose levels, results were comparative to the 0.625 and 1.25 mg conjugated equine estrogen results. Non-hepatic markers (serum gonadotropin, vaginal cytologic studies, urinary calcium levels and urinary calcium/creatinine ratios all increased in dose-dependent fashion. Hepatic markers (hepatic protein level, lipid metabolism, clotting factors, renin substrate) were not affected by transdermal doses of estradiol. Transdermal estradiol provided benefit of increased serum hormone levels without hepatic protein effects of oral conjugated equine estrogens.
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62. - Endocrinological and clinical investigations in post-menopausal women following administration of vaginal cream containing oestriol. Haspels AA, Luisi M, Kicovic PM.
Maturitas 1981;3(3-4):321-7.
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63. - The significance of oestriol in the management of the post-menopause. Tzingounis VA, Aksu MF, Greenblatt RB.
Acta Endocrinol Suppl (Copenh). 1980;233:45-50.
Oral estriol was given for 6 months to 52 postmenopausal women in 4 different dosages: group A received 2 mg/day; group B, 4 mg/day; group C, 6 mg/day; and group D, 8 mg/day. No endometrial proliferation was seen even at the highest dose. Improvements in menopausal symptoms were seen in all groups, but the extent of the symptom relief increased with the dose of estriol. No side effects were seen.
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64. - Estriol in the management of the menopause. Tzingounis VA, Aksu MF, Greenblatt RB.
JAMA 1978;239(16):1638-41.
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65. - Effect of estriol administration on the hypogonadal woman. Schiff I, Wentworth B, Koos B, Ryan KJ, Tulchinsky
Fertil Steril. 1978;30(3):278-82.
Vaginal or oral estriol (0.5 mg) was given to 14 postmenopausal women. When given orally, the estriol was rapidly conjugated, so that most of the estriol was present in a non-biologically active form in the blood. Vaginal treatment resulted in less rapid conjugation, making it more biologically available. Estrogenic effects were observed on the vaginal lining with both treatment forms. Serum levels of unbound estriol after a month of oral treatment were similar to those seen 3 hours after vaginal application of 1/16 of the oral dose. Continuous oral administration of estriol increases its potency, while much lower doses can be used vaginally to achieve similar biological effects.
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66. - Micronized 17 beta-estradiol for oral estrogen therapy in menopausal women. Callantine MR, Martin PL, Bolding OT, Warner PO, Greaney MO Jr.
Obstet Gynecol 1975;46(1):37-41.
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