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Transdermal Estradiol

A Review of its Pharmacological Profile, and Therapeutic Potential in the Prevention of Postmenopausal Osteoporosis

  • Drug Evaluation
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Summary

The estradiol transdermal therapeutic system is a percutaneous delivery device which, when affixed to the skin, delivers estradiol (the major estrogen in premenopausal women) into the systemic circulation at a constant rate for up to 4 days. Because this method of delivery avoids first-pass hepatic metabolism, premenopausal levels of estradiol can be maintained in postmenopausal women using very low dosages.

Bone density decreases at an accelerated rate after the menopause, which can lead to development of osteoporosis and increased fracture risk. In common with other estrogen therapies, transdermal estradiol provides protection against osteoporosis following spontaneous or surgical menopause, as evidenced by both biochemical markers of bone resorption and, in a small number of studies, measurement of bone mineral density. Protection against further vertebral fractures was also demonstrated in women with established osteoporosis in one study. Transdermal estradiol also has beneficial effects on vaginal cytology and menopausal symptoms similar to those of oral estrogens.

The tolerability of transdermal estradiol appears to be very good, the most common adverse effect being local irritation at the application site. As with other estrogens, transdermal estradiol can be given continuously or in 4-week (3 weeks on/1 week off) cycles, and concomitant progestogen therapy is recommended in women with intact uteri, in order to minimise the risk of endometrial hyperplasia.

Available evidence thus suggests that transdermal estradiol may represent an attractive alternative to other forms of estrogen therapy for the prevention, and possibly treatment, of postmenopausal osteoporosis.

Pharmacological Profile

The estradiol transdermal therapeutic system is a controlled-release percutaneous delivery device in the form of a thin adhesive plaster which is affixed to the skin. Systems which are designed to deliver 0.025, 0.05 and 0.1 mg of estradiol per 24 hours for up to 4 days are available.

Maximum plasma estradiol levels are attained within 4 to 8 hours of applying transdermal estradiol systems. Steady-state plasma estradiol levels are dose-proportional, with mean values of approximately 23, 40 and 75 ng/L being achieved in postmenopausal women with pretreatment levels of ⩽ 10 ng/L receiving transdermal estradiol 0.025, 0.05 and 0.1 mg/day, respectively, while a physiological plasma ratio of estradiol to estrone levels is maintained. The estradiol levels achieved with the 2 higher dosages are characteristic of the early to mid follicular stage of the ovulatory cycle.

Estradiol is rapidly cleared from the circulation, with a plasma half-life of approximately 1 hour, whatever the route of administration, and a metabolic clearance rate of between 650 and 900 L/day/mp2. Metabolism occurs mainly in the liver, the major metabolites being estrone and estriol and their conjugates, which are considerably less potent than estradiol. Metabolites are mainly excreted as glucuronide and sulphate conjugates in the urine, although a degree of entero-hepatic recirculation may occur. Plasma levels of estradiol and estrone, and urinary excretion of estradiol and estrone conjugates, revert to pretreatment values within 24 hours of removing transdermal estradiol delivery systems.

In common with other estrogens, transdermal estradiol inhibits bone resorption, as evidenced by reduction in urinary excretion of calcium and hydroxyproline and other metabolic markers of bone resorption, and small increases in bone mineral density (BMD) in postmenopausal women receiving long term treatment.

As a consequence of increased plasma estradiol levels, elevated plasma levels of follicle-stimulating hormone (FSH) and luteinising hormone (LH) are decreased and vaginal cytology is converted to a pattern similar to that found in premenopausal women, with increased numbers of superficial, and decreased numbers of basal and parabasal cells. Characteristic symptoms of the menopause, including hot flushes and vulvovaginal discomfort, are also ameliorated.

Oral estrogens appear to provide protection against cardiovascular disease in postmenopausal women; this protective effect may be partly mediated by changes in the plasma lipid and lipoprotein profiles. While changes in lipid metabolism are less marked with transdermal adminis-tration (presumably because first-pass hepatic metabolism is avoided), potentially beneficial lipid and lipoprotein changes have been observed in patients receiving transdermal estradiol for 4 months or longer.

Therapeutic Efficacy

Data from a small number of clinical trials indicate that long term (⩾ 6 months) transdermal estradiol therapy (which was administered with sequential progestagen in nonhysterectomised, and some hysterectomised, women) prevents bone loss in postmenopausal women, generally producing a modest increase in BMD or bone mineral content (BMC), which has achieved statistical significance vs pretreatment and/or control values in a number of studies. In contrast, BMD and/ or BMC declined significantly in women receiving no treatment, calcium supplements or placebo in comparative studies. Transdermal estradiol was also shown in a single study to significantly decrease the rate of further vertebral fractures versus placebo in postmenopausal women with osteoporotic fractures.

Transdermal estradiol 0.05mg appeared to be as effective in conserving bone in the lumbar spine and proximal femur as oral conjugated estrogens 0.625 mg/day in 2 comparative studies.

Tolerability

The most common problems associated with transdermal estradiol therapy are dermatological reactions to the transdermal delivery system, which occur in a significant and variable proportion of patients. Such reactions mostly consist of transient erythema or itching at the site of application, which can be minimised by selection of new sites when applying patches; however, severe cutaneous irritation necessitating withdrawal of therapy is experienced by a minority of individuals (6.3%, according to manufacturer’s safety data) of patients. Transdermal estradiol is otherwise well tolerated, the most common systemic adverse symptoms being typical dose-related estrogenic effects such as breast tenderness, vaginal spotting/bleeding, fluid retention, headache and nausea.

As with other estrogens, unopposed transdermal estradiol stimulates the endometrium, and concomitant sequential progestagen therapy is recommended in nonhysterectomised women, in order to prevent excessive endometrial proliferation, and improve the bleeding pattern. Proges-togen-related adverse effects (e.g. gastrointestinal disturbances, weight gain, headaches, depression) may occur in women receiving combined estrogen/progestogen therapy.

In contrast to oral estrogens, transdermal estradiol does not stimulate hepatic metabolism and therefore does not elevate plasma levels of renin substrate.

Dosage and Administration

For the prevention of postmenopausal osteoporosis, the recommended initial dosage of transdermal estradiol is 0.05mg daily, which may be adjusted to alleviate any accompanying menopausal symptoms. Treatment may be continuous or may be given in 4-week cycles (3 weeks on/ 1 week off). Sequential progestagen treatment (e.g. medroxyprogesterone acetate 5 to 10mg, nor-ethisterone 1 to 2.5mg or dydrogesterone 20mg, per day) should be administered for 10 to 14 days per month to patients with an intact uterus.

The transdermal estradiol delivery system should be changed twice weekly. Contraindications to the use of estrogens include carcinoma of the breast, estrogen-dependent neoplasms, pregnancy and lactation, vaginal bleeding of unknown origin, and previous estrogen-associated, or active, thromboembolic disease or thrombophlebitis. Estrogens should be prescribed with caution in patients with past or present endometriosis, uterine leiomyomata, impaired hepatic or renal function, conditions likely to be influenced by fluid retention, metabolic bone disease associated with hypercalcaemia, or a history of depression or pregnancy-associated jaundice, and should be discontinued if jaundice develops, or if preexisting uterine leiomyomata increase in size, during treatment.

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References

  • Adami S, Suppi R, Bertoldo F, Rossini M, Residori M, et al. Transdermal estradiol in the treatment of postmenopausal bone loss. Bone and Mineral 7: 79–86, 1989

    Article  PubMed  CAS  Google Scholar 

  • Alkjaersig N, Fletcher AP, De Ziegler D, Steingold KA, Meldrum DR, et al. Blood coagulation in postmenopausal women given estrogen treatment: comparison of transdermal and oral administration. Journal of Laboratory and Clinical Medicine 111: 224–228, 1988

    PubMed  CAS  Google Scholar 

  • Balfour JA, Heel RC. Transdermal estradiol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of menopausal complaints. Drugs 40: 561–582, 1990

    Article  PubMed  CAS  Google Scholar 

  • Boschetti C, Cortellaro M, Nencioni I, Bertolli V, della Volpe A, et al. Short- and long-term effects of hormone replacement therapy (transdermal estradiol vs oral conjugated equine estrogens, combined with medroxyprogesterone acetate) on blood coagulation factors in postmenopausal women. Thrombosis Research 62: 1–8, 1991

    Article  PubMed  CAS  Google Scholar 

  • Bourne T, Hillard TC, Whitehead MI, Crook D, Campbell S. Oestrogens, arterial status and postmenopausal women. Lancet 335: 1470–1471, 1990

    Article  PubMed  CAS  Google Scholar 

  • Bradley D, Wingerd J, Pettiti DB, Krauss RM, Ramcharan S. Serum high-density lipoprotein cholesterol in women using oral contraceptives, estrogens and progestins. New England Journal of Medicine 299: 17–20, 1978

    Article  PubMed  CAS  Google Scholar 

  • Brinton LA, Hoover R, Fraumeni Jr JF. Menopausal oestrogens and breast cancer risk: an expanded case-control study. British Journal of Cancer 54: 825–832, 1986

    Article  PubMed  CAS  Google Scholar 

  • Buring JE, Hennekens CH, Lipnick RJ, Willett W, Stampfer MJ, et al. A prospective cohort study of postmenopausal hormone use and risk of breast cancer in US women. American Journal of Epidemiology 125: 939–947, 1987

    PubMed  CAS  Google Scholar 

  • Bush T, Miller V. Effects of pharmacologic agents used during menopause: impact on lipids and lipoproteins. In Mishell D (Ed) Menopause: physiology and pharmacology, pp. 187–208, Yearbook, Chicago, 1987

    Google Scholar 

  • Bush TL, Barrett-Connor E, Cowan LD, Criqui MH, Wallace RB, et al. Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-Up Study. Circulation 75: 1102–1109, 1987

    Article  PubMed  CAS  Google Scholar 

  • Buvat J, Buvat-Herbaut M, Desmons F, et al. Les patchsà l’estradiol. Un progrès dans le traitement de la ménopause. Gynécologie 40: 53–59, 1989

    Google Scholar 

  • Cagnacci A, Melis GB, Paoletti AM, Gambacciani M, Manetti P, et al. Effeti centrali e periferici della terapia con estradiolo transdermico a breve e lungo termine. Secondo Congresso Nazionale di Scienzi Ginechologiche ed ostetriche, 12–19 June, 1988, p 56

    Google Scholar 

  • Cagnacci A, Soldani R, Carriero PL, Paoletti AM, Fioretti P, et al. Effects of low doses of transdermal 17β-estradiol on carbohydrate metabolism in postmenopausal women. Journal of Clinical Endocrinology and Metabolism 74: 1396–1400, 1992

    Article  PubMed  CAS  Google Scholar 

  • Castelo-Branco C, Martinez de Osaba MJ, Pons F, Gonzalez-Merlo J. The effect of hormone replacement therapy on postmenopausal bone loss. European Journal of Obstetrics and Gynecology and Reproductive Biology 44: 131–136, 1992

    Article  PubMed  CAS  Google Scholar 

  • Chetkowski RJ, Meldrum DR, Steingold KA, Randle D, Lu JK, et al. Biologic effects of transdermal estradiol. New England Journal of Medicine 314: 1615–1620, 1986

    Article  PubMed  CAS  Google Scholar 

  • Christiansen C, Christensen MS, Transbøl IB. Bone mass in postmenopausal women after withdrawal of oestrogen/gestagen replacement therapy. Lancet 2: 459–461, 1981

    Article  Google Scholar 

  • Clisham P, Cedars MI, Greendale G, Fu Y, Gambone J, et al. Long-term transdermal estradiol therapy: effects on endometrial histology and bleeding patterns. Obstetrics and Gynecology 79: 196–201, 1992

    PubMed  CAS  Google Scholar 

  • Colditz GA, Willett WC, Stampfer MJ, Rosner B, Speizer FE, et al. Menopause and the risk of coronary heart disease in women. New England Journal of Medicine 316: 1105–1110, 1987

    Article  PubMed  CAS  Google Scholar 

  • Colvin PL, Auerbach BJ, Koritnik DR, Hazzard WR, Applebaun-Bowden D. Differential effects of oral estrone versus 17β-es-tradiol on lipoproteins in postmenopausal women. Journal of Clinical Endocrinology and Metabolism 70: 1568–1573, 1990

    Article  PubMed  CAS  Google Scholar 

  • Consensus Conference. Osteoporosis. Journal of the American Medical Association 252: 799–802, 1984

    Google Scholar 

  • Consensus Development Conference Report. Consensus development conference: prophylaxis and treatment of osteoporosis. American Journal of Medicine 90: 107–110, 1991

    Article  Google Scholar 

  • Cortellaro M, Nencioni T, Boschetti C, Ortolani S, Buzzi F, et al. Cyclic hormonal replacement therapy after the menopause: transdermal versus oral treatment. European Journal of Clinical Pharmacology 41: 555–559, 1991

    Article  PubMed  CAS  Google Scholar 

  • Crook D, Cust MP, Gangar KF, Worthington M, Hillard TC, et al. Comparison of transdermal and oral estrogen-progestin replacement therapy: effects on serum lipids and lipoproteins. American Journal of Obstetrics and Gynecology 166: 950–955, 1992

    PubMed  CAS  Google Scholar 

  • Davis GF, Winter Jr L. Cumulative irritation study of placebo transdermal estrogen patches. Current Therapeutic Research 42: 712–719, 1987

    Google Scholar 

  • Dupont Wd, Page DL. Menopausal estrogen replacement therapy and breast cancer. Archives of Internal Medicine 151: 67–72, 1991

    Article  PubMed  CAS  Google Scholar 

  • Erkkola R, Holma P, Järvi T, et al. Transdermal oestrogen replacement therapy in a Finnish population. Maturitas 13: 275–281, 1991

    Article  PubMed  CAS  Google Scholar 

  • Fara JW. Short and long term transdermal drug delivery systems. International Two-Day Conference on Drug Delivery Systems, Paris, January 31–February 1, 1983

    Google Scholar 

  • Field CS, Ory SJ, Wahner HW, Hermann RR, Judd HL, et al. Preventive effects of transdermal 17 β-estradiol on osteoporotic changes after surgical menopause: a 2-year placebo-controlled trial. American Journal of Obstetrics and Gynecology, in press, 1992

  • Fioretti P, Gambacciani M, Spinetti A, Cagnacci A, Paoletti AM, et al. Annals of the New York Academy of Sciences 662: 302–306, 1991

    Article  Google Scholar 

  • Gambrell RD. The prevention of endometrial cancer in postmenopausal women with progestogens. Maturitas 1: 107–112, 1978

    Article  PubMed  Google Scholar 

  • Gangar KF, Vyas S, Whitehead MI, Crook D, Meire H, et al. Pulsatility index in internal carotid artery in relation to transdermal oestradiol and time since menopause. Lancet 338: 839–842, 1991

    Article  PubMed  CAS  Google Scholar 

  • Genant HK, Cann CE, Ettinger B, Gordan GS. Quantitative computed tomography of vertebral spongiosa: a sensitive method for detecting early bone loss after oophorectomy. Archives of Internal Medicine 97: 699–705, 1982

    CAS  Google Scholar 

  • Geola FL, Frumar AM, Tataryn IV, Lu KH, Hershman JM, et al. Biological effects of various doses of conjugated equine estrogens in postmenopausal women. Journal of Clinical Endocrinology and Metabolism 51: 620–625, 1980

    Article  PubMed  CAS  Google Scholar 

  • Good WR, Powers MS, Campbell P, Schenkel L. A new transdermal delivery system for estradiol. Journal of Controlled Release 2: 89–97, 1985

    Article  CAS  Google Scholar 

  • Gordon T, Kannel WB, Hjortland MC, McNamara PM. Menopause and coronary heart disease. The Framingham study. Annals of internal Medicine 89: 157–161, 1978

    PubMed  CAS  Google Scholar 

  • Grail JY. Estrogenothérapie substitutive per voie transdermique: sur quels critères choisir la posologie initiale? Tempo Médical 410(Suppl. 1): 1–7, 1990

    Google Scholar 

  • Haas S, Walsh B, Evans S, Krache M, Ravnikar V, et al. The effect of transdermal estradiol on hormone and metabolic dynamics over a six-week period. Obstetrics and Gynecology 71: 671–676, 1988

    PubMed  CAS  Google Scholar 

  • Hansen MA, Overgaard K, Riis BJ, Christiansen C. Role of peak bone mass and bone loss in postmenopausal osteoporosis: a 12 year study. British Medical Journal 303: 961–964, 1991

    Article  PubMed  CAS  Google Scholar 

  • Heaney RP. Estrogens and postmenopausal osteoporosis. Clinical Obstetrics and Gynecology 19: 791–803, 1976

    Article  PubMed  CAS  Google Scholar 

  • Henderson BE, Ross RK, Paganini-Hill A, Mack TM. Estrogen use and cardiovascular disease. American Journal of Obstetrics and Gynecology 154: 1181–1186, 1986

    PubMed  CAS  Google Scholar 

  • Hunt K, Vessey M. Long-term effects of postmenopausal hormone replacement therapy. British Journal of Hospital Medicine (Nov): 450-460, 1987

  • Huppert LC. Hormonal replacement therapy: benefits, risks, doses. Medical Clinics of North America 71: 23–39, 1987

    PubMed  CAS  Google Scholar 

  • Hutchinson TA, Polansky SM, Feinstein AR. Post-menopausal oestrogens protect against fractures of hip and distal radius. Lancet 2: 706–709, 1979

    Google Scholar 

  • Janaud A. Estraderm TTS dans le traitement des troubles liés á la ménopause: résultats d’une étude long terme chez 324 femmes. Gazette Médicale 97: 1–7, 1990

    Google Scholar 

  • Jasonni VM, Bulletti C, Naldi S, Ciotti P, Di Cosmo D, et al. Biological and endocrine aspects of transdermal 17-β oestra-diol administration in post-menopausal women. Maturitas 10: 263–270, 1988

    Article  PubMed  CAS  Google Scholar 

  • Jensen J, Riis BJ, Ström V, Nilas L, Christiansen C. Long-term effects of percutaneous estrogens and oral progesterone on serum lipoproteins in premenopausal women. American Journal of Obstetrics and Gynecology 156: 66–71, 1987

    PubMed  CAS  Google Scholar 

  • Johannisson E, Landgren B-M, Diczfalusy E. Endometrial and vaginal response to three different oestrogen preparations administered by the transdermal and oral routes. Maturitas 10: 181–192, 1988

    Article  PubMed  CAS  Google Scholar 

  • Kerzel C, Keller PJ. Ein transdermales therapeutisches System zue hormonellen Therapie klimakterischer Ausfallserscheinungen. Multizenrische Studie. Geburtshilfe und Frauenheilkunde 47: 565–568, 1987

    Article  PubMed  CAS  Google Scholar 

  • Laufer LR, DeFazio JL, Lu JKH, Meldrum DR, Eggena P, et al. Estrogen replacement therapy by transdermal estradiol administration. American Journal of Obstetrics and Gynecology 146: 553, 1983

    Google Scholar 

  • Lauritzen C. Transdermal delivery of 17-beta estradiol. In Lauritzen C (Ed.) Transdermal estrogen substitution, pp. 82–83, Hans Huber Publishers, Bern, 1987

    Google Scholar 

  • Lauritzen C. Vergleichende Prüfung einer transdermalen Estro-genverabfolgung mittels Pflasteranwendung gegen ein orales Estrogenpräparat. Münchener Medizinische Wochenschrift 130: S66–S68, 1988

    Google Scholar 

  • La Vecchia C, de Carli A, Parrazzini F, Gentile A, Liberati C, et al. Non-contraceptive oestrogens and the risk of breast cancer in women. International Journal of Cancer 38: 853–858, 1986

    Article  Google Scholar 

  • Law MR, Wald NJ, Meade TW. Strategies for prevention of osteoporosis and hip fracture. British Medical Journal 303; 453–459, 1991

    Article  PubMed  CAS  Google Scholar 

  • Lievertz RW. Pharmacology and pharmacokinetics of estrogens. American Journal of Obstetrics and Gynecology 156: 1289–1293, 1987

    PubMed  CAS  Google Scholar 

  • Lindsay R, Hart DM, Clark DM. The minimum effective dose of estrogen for prevention of postmenopausal bone loss. Obstetrics and Gynecology 63: 759–763, 1984

    PubMed  CAS  Google Scholar 

  • Lobo RA. Cardiovascular implications of estrogen replacement therapy. Obstetrics and Gynecology 75 (Suppl.): 18–25, 1990

    Google Scholar 

  • Lufkin EG, Wanner HW, O’Fallon WM, Hodgson SF, Kotowicz MA, et al. Treatment of postmenopausal osteoporosis with transdermal estrogen. Annals of Internal Medicine 117: 1–9, 1992

    PubMed  CAS  Google Scholar 

  • Mandel FP, Geola FL, Lu JKH, Eggena P, Sambhi MP, et al. Biologic effects of various doses of ethinyl estradiol in postmenopausal women. Obstetrics and Gynecology 59: 673–679, 1982

    PubMed  CAS  Google Scholar 

  • Marchesoni D, D’Angelo A, Mozzanega B, Benetolla P, Aprilis M, et al. Terapia ormonale in menopausa e densitometria ossea: effetti del trattamento estrogenico transcutaneo. Third Congress of Societa Italian per la Menopausa, Bologna, pp. 319–322, 1988

    Google Scholar 

  • McBurney EI, Noel SB, Collins JH. Contact dermatitis to transdermal estradiol system. Journal of the American Academy of Dermatology 20: 508–510, 1989

    Article  PubMed  CAS  Google Scholar 

  • McCarthy TG, Dramusic V, Ratnam SS, Cheng EL. Use of two types of estradiol skin patches for menopausal patients in a tropical climate. American Journal of Obstetrics and Gynecology 166: 2005–2010, 1992

    PubMed  CAS  Google Scholar 

  • Melchert F. Ein Transdermales Therapeutisches system im Vergleich zur peororalen Östrogensubstitution für die Behandlung des klimakterischen Syndroms. Münchener Medizinische Wochenschrift 130: S69–S74, 1988

    Google Scholar 

  • Mück AO, Lippert TH, Blümner EG. Transdermal oestradiol Substitution in 15, 194 patients with climacteric symptoms: a multicentre study. Sixth International Congress on the Menopause, Bangkok, Abstract no. 51, 1990

    Google Scholar 

  • Nachtigall LE, Nachtigall RN, Nachtigall RD, Beckman EM. Estrogen replacement therapy I: a 10-year prospective study in the relationship to osteoporosis. Obstetrics and Gynecology 53: 277–281, 1979

    PubMed  CAS  Google Scholar 

  • Nachtigall LE, Utian WH. Comparative efficacy and tolerability of transdermal estradiol and conjugated estrogens — a double-blind multicenter study. Münchener Medizinische Wochenschrift 130: S28–S34, 1988

    Google Scholar 

  • Nichols KC, Schenkel L, Benson H. 17β-Estradiol for postmenopausal estrogen replacement therapy. Obstetrical and Gynecological Survey 39 (Suppl.): 230–245, 1984

    Article  PubMed  CAS  Google Scholar 

  • Nilas L, Christiansen C. The pathophysiology of peri- and postmenopausal bone loss. British Journal of Obstetrics and Gynaecology 96: 580–587, 1989

    Article  PubMed  CAS  Google Scholar 

  • Padwick ML, Endacott J, Whitehead MI. Efficacy, acceptability, and metabolic effects of transdermal estradiol in the management of postmenopausal women. American Journal of Obstetrics and Gynecology 152: 1085–1091, 1985

    PubMed  CAS  Google Scholar 

  • Pattison NS, Uptin T, Knox B, France J. Transdermal oestrogen for postmenopausal women: a double blind crossover comparative study with ethinyl oestradiol. Australian and New Zealand Journal of Obstetrics and Gynaecology 29: 62–65, 1989

    Article  PubMed  CAS  Google Scholar 

  • Place VA, Powers M, Darley PE, Schenkel L, Good WR. A double-blind comparative study of estraderm and premarin in the amelioration of postmenopausal symptoms. American Journal of Obstetrics and Gynecology 152: 1092–1099, 1985

    PubMed  CAS  Google Scholar 

  • Powers MS, Schenkel L, Darley PE, Good WR, Balestra JC. Pharmacokinetics and pharmacodynamics of transdermal dosage forms of H-β estradiol: comparison with conventional oral estrogens used for hormone replacement. American Journal of Obstetrics and Gynecology 152: 1099–1106, 1985

    PubMed  CAS  Google Scholar 

  • Ribot C, Trémollières F, Pouillès JM, Louvet JP, Peyron R. Transdermal administration of 17-β estradiol in postmenopausal women: preliminary results of a longitudinal study. Os-teoporosis 1987: International Symposium on Osteoporosis, Denmark, September 27–October 2, 1987

    Google Scholar 

  • Ribot C, Trémollières F, Pouillès JM, Louvet JP, Peyron R. Preventive effects of transdermal administration of 17-β estradiol on postmenopausal bone loss: a 2-year prospective study. Obstetrics and Gynecology 75 (Suppl.): 42S–46S, 1990

    Google Scholar 

  • Riis BJ, Thomsen K, Strom V, Christiansen C. The effect of percutaneous estradiol and natural progesterone on postmenopausal bone loss. American Journal of Obstetrics and Gynecology 156: 61–65, 1987

    PubMed  CAS  Google Scholar 

  • Sarrel PM, Lindsay D, Rosano GMC, Poole-Wilson PA. Angina and normal coronary arteries in women: gynecologic findings. American Journal of Obstetrics and Gynecology 167: 467–472, 1992

    PubMed  CAS  Google Scholar 

  • Schenkel L, Barlier D, Riera M, Barner A. Transdermal absorption of estradiol from different body sites is comparable. Journal of Controlled Release 4: 195–201, 1986

    Article  CAS  Google Scholar 

  • Schenkel L, Fankhauser P. Transdermal hormone substitution in the climacteric: a combined transdermal delivery system for norethisterone acetate and oestradiol. Abstract 104 from Vth International Congress on the Menopause, Sorrento, April 6–10, 1987

    Google Scholar 

  • Schlensker K-H. Therapie klimakterischer Beschwerden. Vergleichende klinische prüfung von Estraderm TTS und Gynodian Depot. Münchener Medizinische Wochenschrift 130: 558–562, 1988

    Google Scholar 

  • Schwartz BK, Clendenning WE. Allergic contact dermatitis from hydroxypropyl cellulose in a transdermal estradiol patch. Contact Dermatitis 18: 107–107, 1988

    Article  Google Scholar 

  • Selby PL, McGarrigle HG, Peacock M. Comparison of the effects of oral and transdermal oestradiol administration on oestrogen metabolism, protein synthesis, gonadotrophin release, bone turnover and climacteric symptoms in postmenopausal women. Clinical Endocrinology 30: 241–249, 1989

    Article  PubMed  CAS  Google Scholar 

  • Selby PL, Peacock M. Dose dependent response of symptoms, pituitary, and bone to transdermal oestrogen in postmenopausal women. British Medical Journal 293: 1337–1339, 1986b

    Article  PubMed  CAS  Google Scholar 

  • Selby PL, Peacock M. The effect of transdermal oestrogen on bone, calcium-regulating hormones and liver in postmenopausal women. Clinical Endocrinology 25: 543–547, 1986a

    Article  PubMed  CAS  Google Scholar 

  • Sentrakul P, Chompootaweep S, Sintupak S, Tasanapradit P, Tunsaringkarn K, Dusitsin N. Adverse skin reactions to transdermal oestradiol in tropical climate. A comparative study of skin tolerance after using oestradiol patch and gel in Thai postmenopausal women, Maturitas 13: 151–154, 1991

    CAS  Google Scholar 

  • Sitruk-Ware R. Alternative delivery systems for steroid hormones. 5th International Congress on the Menopause, Sorrento, April 6–10, 1987

    Google Scholar 

  • Sitruk-Ware R. Estrogen therapy during menopause. Practical treatment recommendations. Drugs 39: 203–217, 1990

    Article  PubMed  CAS  Google Scholar 

  • Spector TD, Huskisson EC. A rational approach to the prevention and treatment of osteoporosis. Drugs 37: 205–211, 1989

    Article  PubMed  CAS  Google Scholar 

  • Stampfer MJ, Colditz JA, Willett WC, Manson JE, Rosner B, et al. Postmenopausal estrogen therapy and cardiovascular disease. Ten year follow up from the nurses’ health study. New England Journal of Medicine 325: 756–762, 1991

    Article  PubMed  CAS  Google Scholar 

  • Stanczyk FZ, Shoupe D, Nunez V, Macias-Gonzales P, Vijod MA, et al. A randomized comparison of nonoral estradiol delivery in postmenopausal women. American Journal of Obstetrics and Gynecology 159: 1540–1560, 1988

    PubMed  CAS  Google Scholar 

  • Steinberg K, Thacker SB, Smith SJ, Stroup DS, Zack M, et al. A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer. Journal of the American Medical Association 265: 1985–1990, 1991

    Article  PubMed  CAS  Google Scholar 

  • Steingold KA, Laufer L, Chetkowski RJ, DeFazio JD, Matt DW, et al. Treatment of hot flashes with transdermal estradiol administration. Journal of Clinical Endocrinology and Metabolism 61: 627–632, 1985

    Article  PubMed  CAS  Google Scholar 

  • Štěpán JJ, Pospichal J, Schreiber V, Kaňka J, Menšik J, et al. The application of plasma tartrate-resistant acid phosphatase to assess changes in bone resorption in response to artificial menopause and its treatment with estrogen or norethisterone. Calcified Tissue International 45: 273–280, 1989

    Article  PubMed  Google Scholar 

  • Stevenson JC. Pathogenesis, prevention, and treatment of osteoporosis. Obstetrics and Gynecology 75 (Suppl.): 36–41, 1990

    Google Scholar 

  • Stevenson JC, Cust MP, Gangar KF, Hillard TC, Lees B, et al. Effects of transdermal versus oral hormone replacement therapy on bone density in spine and proximal femur in postmenopausal women. Lancet 335: 265–269, 1990

    Article  Google Scholar 

  • Stumpf PG. Pharmacokinetics of estrogen. Obstetrics and Gynecology 75 (Suppl.): 9–14, 1990

    Google Scholar 

  • Torres V, Campos Lopes J, Leite L. Allergic contact dermatitis from nitroglycerin and estradiol transdermal therapeutic systems. Contact Dermatitis 26: 53, 1992

    Article  PubMed  CAS  Google Scholar 

  • Utian WH. Transdermal estradiol overall safety profile. American Journal of Obstetrics and Gynecology 156: 1335–1338, 1987

    PubMed  CAS  Google Scholar 

  • van Erpecum KJ, Henegowen GP, Verschoor I, Stoelwider B, Willekins FL. Differential hepatobiliary effects of oral and transdermal estradiol in postmenopausal women. Gastroenterology 100: 482–488, 1991

    PubMed  Google Scholar 

  • Wallace RB, Hoover J, Barrett-Connor E, Rifkind BM, Hunninghake DB, et al. Altered plasma lipid and lipoprotein levels associated with oral contraceptive and oestrogen use. Lancet 2: 111–115, 1979

    Article  CAS  Google Scholar 

  • Walsh BW, Schiff I, Rosner B, Greenberg L, Ravnikar V, et al. Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins. New England Journal of Medicine 325: 1196–2204, 1991

    Article  PubMed  CAS  Google Scholar 

  • Whitehead MI, Fraser D. The effects of estrogens and progestogens on the endometrium: a modern approach to treatment. Obstetrics and Gynecology Clinics of North America 14; 299–319, 1987

    PubMed  CAS  Google Scholar 

  • Whitehead M, Fraser D, Endacott J. Symptomatic, psychological and endometrial status during transdermal oestradiol and transdermal norethisterone administration. Abstract 103. 5th International Congress on the Menopause, Sorrento, April 6–10, 1987

    Google Scholar 

  • Whitehead MI, Fraser D, Schenkel L, Crook D, Stevenson JC. Transdermal administration of oestrogen/progestagen hormone replacement therapy. Lancet 335: 310–312, 1990a

    Article  PubMed  CAS  Google Scholar 

  • Whitehead MI, Hillard TC, Crook D. The role and use of progestogens. Obstetrics and Gynecology 75 (Suppl.): 59–76, 1990b

    Google Scholar 

  • Whitehead MI, Padwick ML, Endacott J, Pryse-Davies J. Endometrial responses to transdermal estradiol in postmenopausal women. American Journal of Obstetrics and Gynecology 152: 1079–1084, 1985

    PubMed  CAS  Google Scholar 

  • Wolff F. Oestrogen substitution therapy in the menopause. Comparison between a transdermal and an oral application. Münchener Medizinische Wochenschrift 130: 60–65, 1988

    Google Scholar 

  • Young RL, Goldzieher JW. Current status of postmenopausal oestrogen therapy. Drugs 33: 95–106, 1987

    Article  PubMed  CAS  Google Scholar 

  • Zichella L, Polvani F, Bocci A, Bottiglioni F, Cagnazzo G, et al. Nuovo approccio terapeutico alla sindrome climaterica: il 17-beta estradiolo per via transdermica vs estrogeni coniugati equini orali. Ricerca policentrica randomizzata. Third Congress of Società Italiana per la Menopausa, Bologna, pp. 915–921, 1988

    Google Scholar 

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  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, New Zealand

    Julia A. Balfour & Donna McTavish

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  1. Julia A. Balfour
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  2. Donna McTavish
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Various sections of the manuscript reviewed by: S. Adami, Cattedra di Reumatologia, Universita’ degli Studi di Verona, Verona, Italy; J. Drife, Department of Obstetrics and Gynaecology, University of Leeds, Leeds, England; J. Eisman, Bone and Mineral Research Division, Garvan Institute of Medical Research, St Vincent’s Hospital, Darlinghurst, New South Wales, Australia; P. Fioretti, Department of Obstetrics and Gynaecology, University of Pisa School of Medicine, Pisa, Italy; S.T. Haas, Infertility and Reproductive Endocrinology, Brigham and Women’s Hospital, Boston, Massachusetts, USA; G.M. Hall, Department of Rheumatology, St Bartholomew’s Hospital, London, England; N.S. Pattison, Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand; W.H. Utian, Department of Obstetrics and Gynecology, University MacDonald Womens Hospital, Cleveland, Ohio, USA.

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Balfour, J.A., McTavish, D. Transdermal Estradiol. Drug & Aging 2, 487–507 (1992). https://doi.org/10.2165/00002512-199202060-00005

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