Women in Balance

Bioidentical Estrogens (Estradiol, Estriol)

Archer DF; EstroGel Study Group. Percutaneous 17beta-estradiol gel for the treatment of vasomotor symptoms in postmenopausal women. Menopause. 2003 Nov-Dec; 10(6):516-21.
Arrenbrecht S, Boermans AJ. Effects of transdermal estradiol delivered by a matrix patch on bone density in hysterectomized, postmenopausal women: a 2-year placebo-controlled trial. Osteoporos Int 2002;13(2):176-83.
Bruce-Keller AJ, Keeling JL, Keller JN, Huang FF, Camondola S, Mattson MP. Antiinflammatory effects of estrogen on microglial activation. Endocrinology 2000 Oct;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.
Callantine MR, Martin PL, Bolding OT, Warner PO, Greaney MO Jr. Micronized 17 beta-estradiol for oral estrogen therapy in menopausal women. Obstet Gynecol 1975 Jul;46(1):37-41.
Casson PR et al. Oral dehydoepiandrosterone in physiologic doses modulates immune function in postmenopausal women. American Journal of Obstetrics and Gynecology, 1993 Dec;169(6):1536-9.

This prospective, randomized, double-blind, crossover study of 11 subjects evaluated the immune impact of oral DHEA in postmenopausal women. The control group showed marked increase in natural killer cell activity and suppressed increased IL-6 production seen in the placebo group (IL-6 in vitro has been shown to be an important bone resorber). Authors concluded DHEA may have immune modulatory functions in older postmenopausal women and may additionally have an antioncogenic effect.
Cauley JA, Lucas FL, Kuller LH, Stone K, Browner W, Cummings SR. Elevated serum estradiol and testosterone concentrations are associated with a high risk for breast cancer. Study of Osteoporotic Fractures Research Group.Ann Intern Med 1999 Feb 16;130(4 Pt 1):270-7.

This first phase of a four phase study included 244 placebo and 97 study group participants. Results showed that serum total estradiol and bioavailable estradiol were 30% higher and that free testosterone was 28% higher in case study patients. The strongest association between cancer and serum hormone was in bioavailable estrogens – a 3.6 fold greater risk of cancer while total and free testosterone concentrations showed a 3 fold increased cancer risk. The authors suggested that the use of serum bioavailable estradiol and free testosterone levels serve as clinical measures to identify high-risk breast cancer individuals and the use of antiestrogenic treatment to decrease cancer recurrence.
Chan HY, Yao X, Tsang SY, Chan FL, Lau CW, Huang Y. Different role of endothelium/nitric oxide in 17beta-estradiol- and progesterone-induced relaxation in rat arteries. Life Sci 2001 Aug 24;69(14):1609-17
Chetkowski RJ, Meldrum DR, Steingold KA, Randle D, Lu JK, Eggena P, Hershman JM, Alkjaersig NK, Fletcher AP, Judd HL. Biologic effects of transdermal estradiol. 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 relation 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. Nonhepatic 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.
Collette J, Viethel P, Dethor M, Chevallier T, Micheletti MC, Foidart JM, Reginster JY. [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] Gynecol Obstet Fertil. 2003 May;31(5):434-41.
Cohen, L, Soares, C, Poitras, J, Prouty, J, Alexander, A, Shifren, J. Short-term use of estradiol for depression in perimenopausal and postmenopausal women: a preliminary report. Am J Psychiatry. 2003 Aug;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.
Crews JK, Khalil RA. Antagonistic effects of 17 beta-estradiol, progesterone, and testosterone on Ca2+ entry mechanisms of coronary vasoconstriction.Arterioscler Thromb Vasc Biol 1999 Apr;19(4):1034-40.
Darj E, Axelsson O, Carlstrom K, Nilsson S, von Schoultz B. Liver metabolism during treatment with estradiol and natural progesterone. Gynecol Endocrinol 1993 Jun;7(2):111-4.
Davis SR, Walker KZ, Strauss BJ. Effects of estradiol with and without testosterone on body composition and relationships with lipids in postmenopausal women. Menopause 2000 Nov-Dec;7(6):395-401.
de Kleijn MJ, van der Schouw YT, Verbeek AL, Peeters PH, Banga JD, van der Graaf Y. Endogenous estrogen exposure and cardiovascular mortality risk in postmenopausal women. Am J Epidemiol 2002 Feb 15;155(4):339-45.
de Lignieres B, Silberstein S. Pharmacodynamics of oestrogens and progestogens. Cephalalgia 2000 Apr;20(3):200-7.
Djahanbakhch O, Warner P, McNeilly AS, Baird DT. Pulsatile release of LH and oestradiol during the periovulatory period in women. Clin Endocrinol (Oxf) 1984 May;20(5):579-89.
Dorgan JF, Stanczyk FZ, Longcope C, Stephenson HE Jr, Chang L, Miller R, Franz C, Falk RT, Kahle L. Relationship of serum dehydroepiandrosterone (DHEA), DHEA sulfate, and 5-androstene-3 beta, 17 beta-diol to risk of breast cancer in postmenopausal women. Cancer Epidemiol Biomarkers Prev 1997 Mar;6(3):177-81.
Ettinger B, Genant HK, Steiger P, Madvig P. Low-dosage micronized 17 beta-estradiol prevents bone loss in postmenopausal women. American Journal of Obstetrics and Gynecology. 1992 Feb;166(2):479-88.

The authors evaluated the effects of 17 beta-estradiol in a random 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.
Evans SF, Davie MW. Low and conventional dose transdermal oestradiol are equally effective at preventing bone loss in spine and femur at all post-menopausal ages. Clin Endocrinol (Oxf) 1996 Jan;44(1):79-84.
Friel PN, Hinchcliffe C, Wright JV. Hormone replacement with estradiol: conventional oral doses result in excessive exposure to estrone. Altern Med Rev. 2005 Mar;10(1):36-41.
Granberg S, Eurenius K, Lindgren R, Wilhelmsson L. The effects of oral estriol on the endometrium in postmenopausal women. Maturitas 2002 Jun 25;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.
Haines, C, Chung, T, Chang, A, Masarei, J, Tomlinson, B, Wong, E. Effect of oral estradiol on Lp(a) and other lipoproteins in postmenopausal women. A randomized, double-blind, placebo-controlled, crossover study.Arch Intern Med 1996 Apr 22;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 Lp(a) lipoprotein 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. Lp(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 Lp(a) lipoprotein levels with extended oral estrogen therapy support a cardioprotective effect of HRT in postmenopausal women.
Haspels AA, Luisi M, Kicovic PM. Endocrinological and clinical investigations in post-menopausal women following administration of vaginal cream containing oestriol. Maturitas 1981 Dec;3(3-4):321-7.
Hayashi T, Ito I, Kano H, Endo H, Iguchi A. Estriol (E3) replacement improves endothelial function and bone mineral density in very elderly women. J Gerontol A Biol Sci Med Sci 2000 Apr;55(4):B183-90; discussion B191-3.
Head KA. Estriol: safety and efficacy. Altern Med Rev. 1998 Apr;3(2):101-13.
Iosif CS. Effects of protracted administration of estriol on the lower genito urinary tract in postmenopausal women. Arch Gynecol Obstet 1992;251(3):115-20.
Itoi H, Minakami H, Iwasaki R, Sato I. Comparison of the long-term effects of oral estriol with the effects of conjugated estrogen on serum lipid profile in early menopausal women. Maturitas 2000 Oct 31;36(3):217-22.

This was a randomized comparison study with three arms: 2.0mg E3 + 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.
Jarupanich T, Lamlertkittikul S, Chandeying V. Efficacy, safety and acceptability of a seven-day, transdermal estradiol patch for estrogen replacement therapy. J Med Assoc Thai . 2003 Sep;86(9):836-45.
Kainz C, Gitsch G, Stani J, Breitenecker G, Binder M, Schmidt JB. When applied to facial skin, does estrogen ointment have systemic effects? Arch Gynecol Obstet 1993;253(2):71-4.
Koloszar S, Kovacs L. [Treatment of climacteric urogenital disorders with an estriol-containing ointment] Orv Hetil 1995 Feb 12;136(7):343-5.
Lemon HM. Pathophysiologic considerations in the treatment of menopausal patients with oestrogens; the role of oestriol in the prevention of mammary carcinoma. Acta Endocrinol Suppl (Copenh) 1980;233:17-27.
Lindoff C, Peterson F, Lecander I, Martinsson G, Astedt B. Transdermal estrogen replacement therapy: beneficial effects on hemostatic risk factors for cardiovascular disease. Maturitas 1996 May;24(1-2):43-50.
Longcope C. Estriol production and metabolism in normal women. J Steroid Biochem 1984 Apr;20(4B):959-62.
Lose G, Englev E. Oestradiol-releasing vaginal ring versus oestriol vaginal pessaries in the treatment of bothersome lower urinary tract symptoms. BJOG 2000 Aug;107(8):1029-34.
Manonai J, Theppisai U. Effect of oral estriol on urogenital symptoms, vaginal cytology, and plasma hormone level in postmenopausal women. J Med Assoc Thai 2001 Apr;84(4):539-44.
Mauvais-Jarvis P, Kuttenn F, Gompel A, Malet C, Fournier S. [Estradiol-progesterone interaction in normal and pathological human breast cells] Ann Endocrinol (Paris) 1986;47(3):179-87.
Melamed M, Castano E, Notides AC, Sasson S. Molecular and kinetic basis for the mixed agonist/antagonist activity of estriol. Mol Endocrinol 1997 Nov;11(12):1868-78.
Miller BE, De Souza MJ, Slade K, Luciano AA. Sublingual administration of micronized estradiol and progesterone, with and without micronized testosterone: effect on biochemical markers of bone metabolism and bone mineral density. Menopause 2000 Sep-Oct;7(5):318-26.
Nagata C, Shimizu H, Takami R, Hayashi M, Takeda N, Yasuda K. Relations of insulin resistance and serum concentrations of estradiol and sex hormone-binding globulin to potential breast cancer risk factors. Jpn J Cancer Res 2000 Sep;91(9):948-53.
Nahoul K, Dehennin L, Jondet M, Roger M. Profiles of plasma estrogens, progesterone and their metabolites after oral or vaginal administration of estradiol or progesterone. Maturitas 1993 May;16(3):185-202.
Nozaki M, Hashimoto K, Inoue Y, Sano M, Nakano H. [Usefulness of estriol for the treatment of bone loss in postmenopausal women] Nippon Sanka Fujinka Gakkai Zasshi. 1996 Feb;48(2):83-8.
Perera M, Sattar N, Petrie JR, Hillier C, Small M, Connell JM, Lowe GD, Lumsden MA. 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. Journal of Clinical Endocrinology and Metabolism 2001 Mar;86(3):1140-3.

This study showed that transdermal estradiol and oral norethisterone reduce plasma triglyceride and total cholesterol levels, factor VII activity and vonWillebrand 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.
Prestwood KM, Kenny AM, Unson C, Kulldorff M. The effect of low dose micronized 17b-estradiol on bone turnover, sex hormone levels, and side effects in older women: a randomized, double blind, placebo-controlled study. Journal of Clinical Endocrinology and Metabolism 2000 Dec;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 10-28pg/L.
Punnonen R, Vaajalahti P, Teisala K. Local oestriol treatment improves the structure of elastic fibers in the skin of postmenopausal women. Ann Chir Gynaecol Suppl 1987;202:39-41.
Raul, R, Stamm, W. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. The New England Journal of Medicine. 1993;329(11):753-56.

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.
Riedel M, Oeltermann A, Mugge A, Creutzig A, Rafflenbeul W, Lichtlen P. Vascular responses to 17 beta-oestradiol in postmenopausal women. Eur J Clin Invest 1995 Jan;25(1):44-7.
Salem ML, Hossain MS, Nomoto K. Mediation of the immunomodulatory effect of beta-estradiol on inflammatory responses by inhibition of recruitment and activation of inflammatory cells and their gene expression of TNF-alpha and IFN-gamma. Int Arch Allergy Immunol 2000 Mar;121(3):235-45.
Scarabin PY, Alhenc-Gelas M, Plu-Bureau G, Taisne P, Agher R, Aiach M. Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial. Arterioscler Thromb Vasc Biol 1997 Nov;17(11):3071-8.
Schiff I, Tulchinsky D, Ryan KJ, Kadner S, Levitz M. Plasma estriol and its conjugates following oral and vaginal administration of estriol to postmenopausal women: correlations with gonadotropin levels. Am J Obstet Gynecol 1980 Dec 15;138(8):1137-41.
Schmidt IU, Wakley GK, Turner RT. Effects of estrogen and progesterone on tibia histomorphometry in growing rats. Calcif Tissue Int 2000 Jul;67(1):47-52.
Schmidt JB, Binder M, Demschik G, Bieglmayer C, Reiner A. Treatment of skin aging with topical estrogens. Int J Dermatol 1996 Sep;35(9):669-74.
Schmidt JB, Binder M, Macheiner W, Kainz C, Gitsch G, Bieglmayer C. Treatment of skin aging symptoms in perimenopausal females with estrogen compounds. A pilot study. Maturitas 1994 Nov;20(1):25-30.
Singh M. Ovarian hormones elicit phosphorylation of Akt and extracellular-signal regulated kinase in explants of the cerebral cortex. Endocrine 2001 Apr;14(3):407-15.
Snabes, M, Payne, J, Kopelen, H, Dunn, JK, Young, R, Zoghbi, W. Physiologic estradiol replacement therapy and cardiac structure and function in normal postmenopausal women: a randomized, double-blind, placebo-controlled crossover trial. Obstetrics and Gynecology, 1997;89(3):332-39.

In a randomized, double-blind, placebo-controlled, crossover clinical trial of 31 postmenopausal women, average age 59.7 years, using 2.0mg 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).
Suvanto-Luukkonen E, Sundstrom H, Penttinen J, Laara E, Pramila S, Kauppila A. Percutaneous estradiol gel with an intrauterine levonorgestrel releasing device or natural progesterone in hormone replacement therapy. Maturitas 1997 Apr;26(3):211-7.
Tagawa, N, Tamanaka, J, Fujinami, A, Kobayashi, Y, Takaon, T, Fukata, S, Kuma, K, Tada, H, Amino, N. Serum dehydroepiandrosterone, dehydroepiandrosterone Sulfate, and Pregnenolone Sulfate concentrations in patients with hyperthyroidism and hypothyroidism. Clinical Chemistry, 2000;46(4):523-28.

In a comparative study of 46 individuals with untreated thyroid disorders to 43 healthy controls, results showed a significant increase in serum DHEA-S but no change in DHEA for those with hyperthyroidism. In hypothyroidism, both DHEA and DHEA-S were significantly decreased. The serum PREG-S was increased in hyperthyroidism and decreased in hypothyroidism. Serum albumin was decreased in hyperthyroidism and serum SHBG was increased in hyperthyroidism.
Takahashi K, Manabe A, Okada M, Kurioka H, Kanasaki H, Miyazaki K. Efficacy and safety of oral estriol for managing postmenopausal symptoms. Maturitas 2000 Feb 15;34(2):169-77.
Takahashi K, Okada M, Ozaki T, Kurioka H, Manabe A, Kanasaki H, Miyazaki K. Safety and efficacy of oestriol for symptoms of natural or surgically induced menopause. Hum Reprod 2000 May;15(5):1028-36.
Tomaszewski J, Adamiak A, Skorupski P, Rzeski W, Rechberger T. [Effect of 17 beta-estradiol and phytoestrogen daidzein on the proliferation of pubocervical fascia and skin fibroblasts derived from women suffering from stress urinary incontinence]
Ginekol Pol. 2003 Oct;74(10):1410-4.
Tzingounis VA, Aksu MF, Greenblatt RB. Estriol in the management of the menopause. JAMA 1978 Apr 21;239(16):1638-41.
Wren BG, Day RO, McLachlan AJ, Williams KM. Pharmacokinetics of estradiol, progesterone, testosterone and dehydroepiandrosterone after transbuccal administration to postmenopausal women. Climacteric. 2003 Jun;6(2):104-11.
Wiebke, A, Callies, F, Van Vlijmen, J, Koehler, I, Reincke, M, Bidlingmaier, M, Huebler, D, Oettel, M, Ernst, M, Schulte, H, Allolio, B. Dehydroepiandrosterone replacement in women with adrenal insufficiency. The New England Journal of Medicine , 1999;341(14):1013-19.

This double-blind crossover study reviewed alternately the effects of 50mg of oral dehydroepiandrosterone(DHEA)daily with placebo in 24 women with adrenal insufficiency. Participants were evaluated using established well-being (depression and anxiety scores) and sexuality (thoughts, interest, satisfaction) scales and serum profiles. Results showed that serum DHEA, DHEA-S and active androgen increased to normal or low-normal levels during treatment. SHBG levels were significantly lower following treatment. IGF-I concentrations increased after treatment (only in women with primary adrenal insufficiency), but IGF-binding protein 3 levels did not change. Serum total and HDL lipoprotein cholesterol levels decreased significantly during treatment. LDL and triglyceride concentrations did not change significantly. Psychological testing scores for well-being and sexuality both improved significantly during treatment. These effects were noticed after treatment for four months, but not after treatment for one month. Authors recommended that treatment with DHEA should be part of hormone replacement therapy for women with adrenal insufficiency.
Wise PM. Estradiol: a protective factor in the adult brain. J Pediatr Endocrinol Metab 2000;13 Suppl 6:1425-9.
Wise P. Estradiol exerts neuroprotective actions against ischemic brain injury: insights derived from animal models. Endocrine. 2003 Jun;21(1):11-5.
Yang TS, Tsan SH, Chang SP, Ng HT. Efficacy and safety of estriol replacement therapy for climacteric women. Zhonghua Yi Xue Za Zhi ( Taipei ). 1995 May;55(5):386-91.
Yoshimura T, Okamura H. Short term oral estriol treatment restores normal premenopausal vaginal flora to elderly women. Maturitas 2001 Sep 28;39(3):253-7.
Yoshimura T, Okamura H. Short term oral estriol treatment restores normal premenopausal vaginal flora to elderly women. Maturitas 2001 Sep 28;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.
Zegura B, Keber I, Sebestjen M, Borko E. Orally and transdermally replaced estradiol improves endothelial function equally in middle-aged women after surgical menopause. Am J Obstet Gynecol. 2003 May;188(5):1291-6.
Zegura B, Keber I, Sebestjen M, Koenig W. Double blind, randomized study of estradiol replacement therapy on markers of inflammation, coagulation and fibrinolysis. Atherosclerosis. 2003 May;168(1):123-9.
Zegura B, Keber I, Sebestjen M, Borko E. Orally and transdermally replaced estradiol improves endothelial function equally in middle-aged women after surgical menopause. American Journal of Obstetrics and Gynecology. 2003 May;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.

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