Unscheduled bleeding during initiation of continuous combined hormone replacement therapy: A direct comparison of two combinations of norethindrone acetate and ethinyl estradiol to medroxyprogesterone acetate and conjugated equine estrogens

James A. Simon, James P. Symons, A. Marcadis, M. Nunez, J. Guarneri, J. Stoukides, S. L. Miaskiewicz, L. Corm, N. Stuccio-White, R. Corbin, M. Gutierrez, S. Weiss, D. Portman, R. Wolff, P. Marx, D. W. Baldwin, E. Boling, S. Silverman, R. Wasnich, G. ClarkR. Emkey, M. Greenwald, A. Kivitz, R. Lnag, B. Drinkwater, P. Welch, J. Aloia, M. Bolognese, G. Woodson, G. Redmond, L. Speroff, B. Soltes, E. Bronsky, J. C. Gallagher, G. Bachman, G. Ebert, H. Resnick, M. Rosenstein, J. Liu, B. Carr, S. Rosenblatt, R. Young, C. Rosen, J. Baker, S. Songcharoen, J. McKenney, B. Zedler, G. Moyer, I. Kerber, O. Gluck, A. Moffett, S. Blank, S. Miller, W. Turner, J. Fearl, C. Wysham, E. Gillie, P. Miller, E. Schwartz, J. Krug, B. Williams

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Objective: To determine whether there are differences between continuous combined hormone replacement therapies on bleeding control. Design: Nine hundred and forty-five postmenopausal women were randomized to one of seven double-blind treatment groups (placebo, 0.25 mg norethindrone acetate (NA)/5 μg ethinyl estradiol (EE), 1 mg NA/5 μg EE, 0.5 mg NA/10 μg EE, 1 mg NA/10 μg EE, 5 μg EE, and 10 μ EE) or unmasked 0.625 mg conjugated equine estrogens (CEE)/2.5 mg medroxyprogesterone acetate (MPA). Treatment was for 12 months; subjects kept daily diaries recording whether they had bleeding and/or spotting. Results: The results focused on currently commercially available hormone replacement therapy products (femhrt [1 mg NA/5 μg EE] and Prempro [0.625 mg CEE/2.5 mg MPA]) as well as a high-dose NA/EE dose combination (1/10) over the first 6 months of use, the most critical period in establishing treatment adherence. At the end of month 6 there was a greater incidence of amenorrhea with both NA/EE dose combinations compared with CEE/MPA (p = 0.009 for 1 mg NA/5 μg EE andp = 0.006 for 1 mg NA/10 μg EE). Statistically significantly more women were amenorrheic at every month based on cumulative amenorrhea for 1 mg NA/5 μg (p < 0.05) compared with CEE/MPA; at months 3 and 6 more women were amenorrheic on 1 mg NA/10 μg EE compared with CEE/MPA using the cumulative amenorrhea parameter. Conclusions: The results indicate that statistically significantly more women attained amenorrhea based on various parameters when administered continuous combined NA/EE compared with CEE/MPA. The potential for long-term treatment compliance based on better bleeding control may optimize the opportunity to prevent osteoporosis as well as other associated health benefits.

Original languageEnglish (US)
Pages (from-to)321-327
Number of pages7
JournalMenopause
Volume8
Issue number5
DOIs
StatePublished - 2001

Keywords

  • Ethinyl estradiol
  • Hormone replacement therapy bleeding
  • Norethindrone
  • Treatment adherence

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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