Compliance considerations with estrogen replacement: Withdrawal bleeding and other factors

  • Ricardo G. Hahn
    Reprint requests: Ricardo G. Hahn, MD, Department of Family Medicine, University of Tennessee, 1121 Union Ave., Memphis, TN 38104.
    Memphis, Tennessee, From the Department of Family Medicine, University of Tennessee at Memphis.
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      Withdrawal bleeding and other side effects such as edema, bloating, premenstrual irritability, lower abdominal cramps, dysmenorrhea, and breast tenderness limit compliance with hormonal replacement therapy. Although many of these troublesome side effects can be managed by adjusting the dose or changing the source of the estrogen or progestin components, postmenopausal women view withdrawal bleeding as the most negative factor influencing their decision to use hormonal replacement therapy. Additionally, the potential link between postmenopausal estrogen use and subsequent endometrial hyperplasia and cancer concerns potential users. Cyclic progestins protect the endometrium from hyperplastic changes but may not prevent withdrawal bleeding. Both patient and physician education, including the nature of menopause and the protective role of estrogens in osteoporosis and cardiovascular disease, are critical to improving compliance with hormonal replacement therapy.

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        • Ferguson KJ
        • Hoegh C
        • Johnson S
        Estrogen replacement therapy: a survey of women's knowledge and attitudes.
        Arch Intern Med. 1989; 149: 133-136
        • Richards-Kuston CJ
        • Kase NG
        Diagnosis and management of perimenopausal bleeding.
        Obst Gynecol Clin North Am. 1987; 14: 169-189
        • Davis ME
        • Lanzi L
        • Cox AB
        Detection, prevention, and retardation of menopausal osteoporosis.
        Obstet Gynecol. 1970; 36: 187-198
        • Lindsay R
        • Hart DM
        • Aitken JM
        • et al.
        Long-term prevention of postmenopausal osteoporosis by oestrogen.
        Lancet. 1976; 1: 1038-1041
        • Nachtigall LE
        • Nachtigall RH
        • Nachtigall RD
        • et al.
        Estrogen replacement therapy I: a ten-year prospective study in the relationship to osteoporosis.
        Obstet Gynecol. 1979; 53: 277-281
        • Weiss NS
        • Ure CL
        • Ballard JH
        • et al.
        Decreased risk of fractures of the hip and lower forearm with postmenopausal use of estrogen.
        N Engl J Med. 1980; 303: 1195-1198
        • Paganini-Hill A
        • Ross RK
        • Gerkins UR
        • et al.
        Menopausal estrogen therapy and hip fractures.
        Ann Intern Med. 1981; 95: 28-31
        • Kiel DP
        • Felson DT
        • Anderson JJ
        • et al.
        Hip fractures and the use of estrogens in postmenopausal women: the Framingham study.
        N Engl J Med. 1987; 317: 1169-1174
        • Bain C
        • Willet W
        • Hennekena CH
        • et al.
        Use of postmenopausal hormones and risk of myocardial infarction.
        Circulation. 1981; 64: 42-46
        • Ross RK
        • Paganini-Hill A
        • Mack TM
        Menopausal estrogen therapy and protection from death from ischemic heart disease.
        Lancet. 1981; 1: 858-860
        • Hammond CB
        • Jelovsek FR
        • Lee KL
        • et al.
        Effects of long-term estrogen replacement therapy II. Neoplasia.
        Am J Obstet Gynecol. 1979; 133: 537-547
        • Hahn RG
        • Nachtigall RD
        • Davies TC
        Compliance difficulties with progestin supplemented replacement therapy.
        J Fam Pract. 1984; 18: 411-414
        • Prough SG
        • Aksel S
        • Wiebe RH
        • et al.
        Continuous estrogen/progestin therapy in menopause.
        Am J Obstet Gynecol. 1987; 157: 1449-1453
        • Gambrell RD
        Clinical use of progestins in the menopausal patient.
        J Reprod Med. 1982; 27: 531-538
        • Magos AL
        • Brincat M
        • Studd WW
        • et al.
        Amenorrhea and endometrial atrophy with continuous oral estrogen and progestogen therapy in postmenopausal women.
        Obstet Gynecol. 1985; 65: 496-499
        • Whitehead MI
        Prevention of endometrial abnormalities.
        Acta Obstet Gynecol Scand Suppl. 1986; 134: 81-91
        • Whitehead MI
        The effects o f oestrogens and progestogens on the postmenopausal endometrium.
        Maturitas. 1978; 1: 87-98
        • Schiff I
        • Sela NK
        • Cramer D
        • et al.
        Endometrial hyperplasia in women on cyclic or continuous estrogen replacements.
        Fertil Steril. 1982; 37: 79-82
        • Studd JWW
        • Thom MH
        • Paterson MEL
        • et al.
        The prevention and treatment of endometrial pathology in postmenopausal women receiving exogenous estrogen.
        in: Pasetto N Pavletti R Ambrus JL The menopause and postmenopause. MTP Press, Lancaster, England1980: 127-139
        • Whitehead MI
        • Townsend PT
        • Pryse-Davies J
        • et al.
        Effects of various types and dosages of progestogens on the postmenopausal endometrium.
        J Reprod Med. 1982; 27: 539-548
        • Thom MH
        • White PJ
        • Williams RM
        • et al.
        Prevention and treatment of endometrial disease in climateric women receiving oestrogen therapy.
        Lancet. 1978; 2: 455-457
        • Sturdee DW
        • Wade-Evans T
        • Paterson MEL
        • et al.
        Relationships between bleeding pattern, endometrial histology and oestrogen treatment in menopausal women.
        Br Med J. 1978; 1: 1575-1577
        • Wentz WB
        Progestin therapy in endometrial hyperplasia.
        Gynecol Oncol. 1974; 2: 362-367
        • Wren BG
        • Brown LB
        • Routledge DA
        Differential clinical response to oestrogens after menopause.
        Med J Aust. 1982; 2: 329-332
        • Staland B
        Continuous treatment with natural oestrogens and progestogens. A method to avoid endometrial stimulation.
        Maturitas. 1981; 3: 145-156
        • Mattson LA
        • Cullberg G
        • Samsive G
        Evaluation of a continuous oestrogen-progestogen regimen for climateric complaints.
        Maturitas. 1982; 4: 95-102
        • Weinstein L
        Efficacy of a continuous estrogen-progestin regimen in the menopausal patient.
        Obstet Gynecol. 1987; 69: 929-932
        • Luciano AA
        • Turksoy RN
        • Caleo J
        • et al.
        Clinical and metabolic responses of menopausal women to sequential vs continuous estrogen and progestin replacement therapy.
        Obstet Gynecol. 1988; 71: 39-43
        • Ravnikar VA
        Compliance with hormone therapy.
        Am J Obstet Gynecol. 1987; 156: 1332-1334
        • Holzman GB
        • Ravitch MM
        • Metheny W
        • et al.
        Physician's judgments about estrogen replacement therapy for menopausal women.
        Obstet Gynecol. 1984; 63: 303-311
        • Weinstein CW
        • Schiff I
        Cost-effectiveness of hormone replacement therapy in the menopause.
        Obstet Gynecol Surv. 1983; 38: 445-455
        • Cornier E
        The pipelle: a disposable device for endometrial biopsy.
        Am J Obstet Gynecol. 1984; 148: 109-110
        • Kaunitz AM
        • Masciello A
        • Ostrowski M
        • et al.
        Comparison of endometrial biopsy with the endometrial pipelle and vabra aspirator.
        J Reprod Med. 1988; 33: 427-430