Research Article| Volume 14, ISSUE 1, P143-167, March 1987

Absorption and Metabolic Effects of Different Types of Estrogens and Progestogens

  • Rogerio A. Lobo
    Department of Obstetrics and Gynecology, University of Southern California Medical Center, Women's Hospital, Room 1M2, 1240 North Mission Road, Los Angeles, California 90033
    Associate Professor of Obstetrics and Gynecology, University of Southern California School of Medicine, and Chief of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Los Angeles County/University of Southern California Medical Center, Los Angeles, California
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      The classes of estrogens and progestogens currently in use and their routes of administration have been considered. The decision to prescribe any given estrogen or progestogen and by a particular route has a significant impact on cardiovascular risk factors. Among the estrogens, native estradiol and estrone are favored over equine and synthetic estrogens. Given this choice, oral and systemic routes of administration are not sufficiently different clinically to endorse one method over the other, except for the unusual hypertensive woman or the patient with a history of thromboembolic phenomena. Among the progestogens, oral micronized progesterone offers much promise for use in postmenopausal women. However, the oral use of lower doses of other progestogens seems appropriate at the present time. With the availability of oral micronized progesterone and in time a transdermal system, the need for alternate routes of administration for other progestogens seems unnecessary.
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        • Ackerman GE
        • Smith ME
        • Mendelson CR
        • et al.
        Aromatization of androstenedione by human adipose tissue stromal cells in monolayer culture.
        J Clin Endocrinol Metabol. 1981; 53: 412
        • Anderson ABM
        • Sklovsky E
        • Sayers L
        • et al.
        Comparison of serum oestrogen concentrations in postmenopausal women taking oestrone sulphate and oestradiol.
        Br Med J. 1978; 1: 140
        • Aylward M
        • Maddock J
        • Lewis PA
        • et al.
        Oestrogen replacement therapy and blood clotting.
        Curr Med Res Opin. 1977; 4: 83
        • Aylward M
        • Maddock J
        • Rees PL
        Natural oestrogen replacement therapy and blood clotting.
        Br Med J. 1976; 1: 220
        • Barnes RB
        • Roy S
        • Lobo RA
        Comparison of lipid and androgen levels after conjugated estrogen or depo-medroxyprogesterone acetate treatment in postmenopausal women.
        Obstet Gynecol. 1985; 66: 216
        • Burnier AM
        • Martin PL
        • Yen SSC
        • et al.
        Sublingual absorption of micronized 17β-estradiol.
        Am J Obstet Gynecol. 1981; 140: 146
        • Campbell S
        • Whitehead MI
        Potency and hepato-cellular effects of oestrogens after oral, percutaneous and subcutaneous administration.
        in: Van Keep PA Utian WH Vermeulen A The Controversial Climacteric. MTP Press, Lancaster, UK1982
        • Chetkowski RJ
        • Meldrum DR
        • Steingold KA
        • et al.
        Biologic effects of transdermal estradiol.
        N Engl J Med. 1986; 314: 1615
        • Clarke CL
        • Adams JB
        • Wren BG
        Induction of estrogen sulfotransferase in the human endometrium by progesterone in organ culture.
        J Clin Endocrinol Metabol. 1982; 55: 70
        • Conrad J
        • Cazenave B
        • Samama M
        Antithrombin III content and antithrombin activity in estrogen-progestogen and progestogen-only treated women.
        Thromb Res. 1980; 18: 675
        • Cornette JC
        • Kirton KT
        • Duncan GW
        Measurement of medroxyprogesterone acetate by radioimmunoassay.
        J Clin Endocrinol Metabol. 1971; 33: 459
        • Dada OA
        • Laumas V
        • Landgren BM
        • et al.
        Effect of graded oral doses of oestradiol on circulating hormonal levels.
        Acta Endocrinol. 1978; 88: 754
        • Fotherby K
        Variability of pharmacokinetic parameters for contraceptive steroids.
        J Steroid Biochem. 1983; 19: 817
        • Fahraeus L
        • Sydsjo A
        • Wallentin L
        Lipoprotein changes during treatment of pelvic endometriosis with medroxyprogesterone acetate.
        Fertil Steril. 1986; 45: 503
        • Geola FL
        • Frumar AM
        • Tataryn IV
        • et al.
        Biological effects of various doses of conjugated equine estrogens in postmenopausal women.
        J Clin Endocrinol Metabol. 1980; 51: 620
        • Gibbons WE
        • Moyer DL
        • Lobo RA
        • et al.
        Biochemical and histologic effects of sequential estrogen/progestin therapy on the endometrium of postmenopausal women.
        Am J Obstet Gynecol. 1986; 154: 456
        • Goebelsmann U
        • Mashchak CA
        • Mishell Jr, DR
        Comparison of hepatic impact of oral and vaginal administration of ethinyl estradiol.
        Am J Obstet Gynecol. 1985; 151: 868
        • Grodin JM
        • Siiteri PK
        • MacDonald PC
        Source of estrogen production in postmenopausal women.
        J Clin Endocrinol Metabol. 1973; 36: 207
        • Hawkins RA
        • Oakey RE
        Estimation of oestrone sulphate, oestradiol-17β and oestrone in peripheral plasma: concentrations during the menstrual cycle and in men.
        J Endocrinol. 1974; 60: 3
        • Hemsell DL
        • Grodin JM
        • Brenner PF
        • et al.
        Plasma precursors of estrogen. II. Correlation of the extent of the conversion of plasma androstenedione to estrone with age.
        J Clin Endocrinol Metabol. 1974; 38: 476
        • Henderson BE
        • Ross RK
        • Paganini-Hill A
        • et al.
        Estrogen use and cardiovascular disease.
        Am J Obstet Gynecol. 1986; 154: 1181
        • Hirvonen E
        • Malkonen M
        • Manninen V
        Effect of different progestogens on lipoproteins during postmenopausal replacement therapy.
        N Engl J Med. 1981; 304: 560
        • Humpel M
        • Wendt H
        • Pommerenke G
        • et al.
        Investigations of pharmacokinetics of levonorgestrel to specific consideration of a possible first-pass effect in women.
        Contraception. 1978; 17: 207
        • Jasonni M
        • Bulletti C
        • Franceschetti F
        • et al.
        Metabolic clearance rate of oestrone sulphate in post-menopausal women.
        Maturitas. 1984; 5: 251
        • Jensen J
        • Christiansen C
        • Rødbro P
        Cigarette smoking, serum estrogens, and bone loss during hormone-replacement therapy early after menopause.
        N Engl J Med. 1985; 313: 973
        • King RJB
        • Dyer G
        • Collins WP
        • et al.
        Intracellular estradiol, estrone and estrogen receptor levels in endometria from postmenopausal women receiving estrogens and progestins.
        J Steroid Biochem. 1980; 13: 377
        • Laufer LR
        • DeFazio JL
        • Lu JKH
        • et al.
        Estrogen replacement therapy by transdermal estradiol administration.
        Am J Obstet Gynecol. 1983; 146: 533
        • Lund T
        • Cameron EC
        • Hunter WM
        • et al.
        A prospective, controlled trial of six forms of hormone replacement therapy given to postmenopausal women.
        Br J Obstet Gynaecol. 1979; 86: 1
        • Lobo RA
        • Brenner P
        • Mishell Jr, DR
        Metabolic parameters and steroid levels in postmenopausal women receiving lower doses of natural estrogen replacement.
        Obstet Gynecol. 1983; 62: 94
        • Lobo RA
        • March CM
        • Goebelsmann U
        Subdermal estradiol pellets following hysterectomy and oophorectomy.
        Am J Obstet Gynecol. 1980; 138: 714
        • Lobo R
        • Nguyen H
        • Eggena P
        • et al.
        Biological effects of equelin sulfate (EqS): differences in hepatic and bone resorbing effects. Submitted for possible presentation at the 34th Annual Meeting of the Society for Gynecologic Investigation, March 18–21, 1987, Atlanta, Georgia 32. Luotola H: Blood pressure and hemodynamics in postmenopausal women during estradiol-17β substitution.
        Ann Clin Res. 1983; 15: 9
        • Mandel FP
        • Davidson BJ
        • Erlik Y
        • et al.
        Effects of progestins on bone metabolism in postmenopausal women.
        J Reprod Med. 1982; 27: 511
        • Mandel FP
        • Geola FL
        • Lu JKH
        • et al.
        Biologic effects of various doses of ethinyl estradiol in postmenopausal women.
        Obstet Gynecol. 1982; 59: 673
        • Mandel FP
        • Geola FL
        • Meldrum DR
        • et al.
        Biological effects of various doses of vaginally administered conjugated equine estrogens in postmenopausal women.
        J Clin Endocrinol Metabol. 1983; 57: 133
        • Martin PL
        • Greaney MO
        • Burnier AM
        • et al.
        Estradiol, estrone, and gonadotropin levels after use of vaginal estradiol.
        Obstet Gynecol. 1984; 63: 441
        • Mashchak CA
        • Lobo RA
        • Dozono-Takano R
        • et al.
        Comparison of pharmacodynamic properties of various estrogen formulations.
        Am J Obstet Gynecol. 1982; 144: 511
        • Michnovicz JJ
        • Hershcopf RJ
        • Naganuma H
        • et al.
        Increased 2-hydroxylation of estradiol as a possible mechanism for the anti-estrogenic effect of cigarette smoking.
        N Engl J Med. 1986; 315: 1305
        • Nagamani M
        • Lin TJ
        • McDonough PG
        • et al.
        Clinical and endocrine studies in menopausal women after estradiol pellet implantation.
        Obstet Gynecol. 1977; 50: 541
        • Nichols KC
        • Schenkel L
        • Benson H
        17β-estradiol for postmenopausal estrogen replacement therapy.
        Obstet Gynecol Surv. 1984; 39: 230
        • Nillius SJ
        • Johansson EDB
        Plasma levels of progesterone after vaginal, rectal or intramuscular administration of progesterone.
        Am J Obstet Gynecol. 1971; 110: 470
        • Notelovitz M
        • Kitchens C
        • Ware M
        • et al.
        Combination of estrogen and progestogen replacement therapy does not adversely affect coagulation.
        Obstet Gynecol. 1983; 62: 596
        • Ottosson UB
        • Carlstrom K
        • Damber JE
        • et al.
        Serum levels of progesterone and some of its metabolites including deoxycorticosterone after oral and parenteral administration.
        Br J Obstet Gynaecol. 1984; 91: 1111
        • Ottosson UB
        • Carlstrom K
        • Damber JE
        • et al.
        Conversion of oral progesterone into deoxycorticosterone during postmenopausal replacement therapy.
        Acta Obstet Gynecol Scand. 1984; 63: 577
        • Ottosson UB
        • Johansson BG
        • von Schoultz B
        Subfractions of high-density lipoprotein cholesterol during estrogen replacement therapy: a comparison between progestogens and natural progesterone.
        Am J Obstet Gynecol. 1985; 151: 746
        • Padwick M
        • Endacott J
        • Matson C
        • et al.
        Absorption and metabolism of oral progesterone when administered twice daily.
        Fertil Steril. 1986; 46: 402
        • Place VA
        • Powers M
        • Darley PE
        • et al.
        A double-blind comparative study of Estraderm and Premarin in the amelioration of postmenopausal symptoms.
        Am J Obstet Gynecol. 1985; 152: 1092
        • Riggs LA
        • Milanes B
        • Villanueva B
        • et al.
        Efficacy of intravaginal and intranasal administration of micronized estradiol-17β.
        J Clin Endocrinol Metabol. 1977; 45: 1261
        • Ross RK
        • Paganini-Hill A
        • Mack TM
        • et al.
        Estrogen use and cardiovascular disease.
        in: Mishell Jr, DR Menopause: Physiology and Pharmacology. Year Book Medical Publishers, Inc, Chicago, Illinois1986
        • Ruder HJ
        • Loriaux L
        • Lipsett MB
        Estrone sulfate: production rate and metabolism in man.
        J Clin Invest. 1972; 51: 1020
        • Sharf M
        • Oettinger M
        • Lanir A
        • et al.
        Lipid and lipoprotein levels following pure estradiol implantation in post menopausal women.
        Gynecol Obstet Invest. 1985; 19: 207
        • Schiff I
        • Tulchinsky D
        • Ryan KJ
        Vaginal absorption of estrone and 17β-estradiol.
        Fertil Steril. 1977; 28: 1063
        • Sherman BM
        • West JH
        • Korenman SG
        The menopausal transition: analysis of LH, FSH, estradiol, and progesterone concentrations during menstrual cycles of older women.
        J Clin Endocrinol Metabol. 1976; 42: 629
        • Shionoiri H
        • Eggena P
        • Barrett JD
        • et al.
        An increase in high-molecular weight renin substrate associated with estrogenic hypertension.
        Biochem Med. 1983; 29: 14
        • Spellacy WN
        Menopause, estrogen treatment, and carbohydrate metabolism.
        in: Mishell Jr, DR Menopause: Physiology and Pharmacology. Year Book Medical Publishers, Inc, Chicago, Illinois1986
        • Spellacy WN
        • Buhi WC
        • Birk SA
        • et al.
        The effect of estrogens on carbohydrate metabolism: glucose, insulin, and growth hormone studies on one hundred and seventy-one women ingesting Premarin, mestranol and ethyl estradiol for six months.
        Am J Obstet Gynecol. 1972; 114: 378
        • Staland B
        Treatment of menopausal oestrogen deficiency symptoms in hysterectomised women by means of 17β-oestradiol pellet implants.
        Acta Obstet Gynecol Scand. 1978; 57: 281
        • Steege JF
        • Rupp SL
        • Stout AL
        • et al.
        Bioavailability of nasally administered progesterone.
        Fertil Steril. 1986; 46: 727
        • Steingold KA
        • Cefalo W
        • Pardridge W
        • et al.
        Enhanced hepatic extraction of estrogens used for replacement therapy.
        J Clin Endocrinol Metabol. 1986; 62: 761
        • Stumpf PG
        • Maruca J
        • Santen RJ
        • et al.
        Development of a vaginal ring for achieving physiologic levels of 17β-estradiol in hypoestrogenic women.
        J Clin Endocrinol Metabol. 1982; 54: 208
        • Strecker JR
        • Lauritzen C
        • Goessens L
        Plasma concentrations of unconjugated and conjugated estrogens and gonadotropins following application of various estrogen preparations after oophorectomy and in the menopause.
        Maturitas. 1979; 1: 183
        • Thijssen JHH
        • Wiegerinck MAHM
        • Mulder G
        • et al.
        On the biological activity of estrone in vivo.
        Front Hormone Res. 1978; 5: 220
        • Thorn MH
        • Collins WP
        • Studd JWW
        Hormonal profiles in postmenopausal women after therapy with subcutaneous implants.
        Br J Obstet Gynaecol. 1981; 88: 416
        • Verheugen C
        • Pardridge WM
        • Judd HL
        • et al.
        Differential permeability of uterine and liver vascular beds to estrogens and estrogen conjugates.
        J Clin Endocrinol Metabol. 1984; 59: 1128
        • Whitehead MI
        Exogenous oestrogens and the postmenopausal endometrium.
        in: Whitehead MI Campbell S Oestrogen and the Menopause. Abbott Laboratories Ltd, Queenborough, Kent, UK1978
        • Whitehead MI
        • Siddle NC
        • Townsend PT
        • et al.
        The use of progestins and progesterone in the treatment of climacteric and postmenopausal symptoms.
        in: Bardin CW Milgrom E Mauvis-Jarvis P Progesterone and Progestin. Raven Press, New York, NY1982
        • Whitehead MI
        • Townsend PT
        • Gill DK
        • et al.
        Absorption and metabolism of oral progesterone.
        Br Med J. 1980; 280: 825
        • Whitehead MI
        • Townsend PT
        • Kitchin Y
        • et al.
        Plasma steroid and protein hormone profiles in post-menopausal women following topical administration of oestradiol 17β.
        in: Mauvais-Jarvis P Vickers CFH Wepierre J Percutaneous Absorption of Steroids. Academic Press, London, UK1980
        • Wren BG
        • Brown LB
        • Routledge DA
        Differential clinical response to oestrogens after menopause.
        Med J Aust. 1982; 2: 329