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, John Christopher G. 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 journalArticle

20 Citations (Scopus)

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

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Conjugated (USP) Estrogens
Medroxyprogesterone Acetate
Ethinyl Estradiol
Hormone Replacement Therapy
Hemorrhage
Amenorrhea
norethindrone acetate
Metrorrhagia
Insurance Benefits
Therapeutics
Osteoporosis

All Science Journal Classification (ASJC) codes

  • Obstetrics and Gynecology

Cite this

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

In: Menopause, Vol. 8, No. 5, 2001, p. 321-327.

Research output: Contribution to journalArticle

Simon, JA, Symons, JP, Marcadis, A, Nunez, M, Guarneri, J, Stoukides, J, Miaskiewicz, SL, Corm, L, Stuccio-White, N, Corbin, R, Gutierrez, M, Weiss, S, Portman, D, Wolff, R, Marx, P, Baldwin, DW, Boling, E, Silverman, S, Wasnich, R, Clark, G, Emkey, R, Greenwald, M, Kivitz, A, Lnag, R, Drinkwater, B, Welch, P, Aloia, J, Bolognese, M, Woodson, G, Redmond, G, Speroff, L, Soltes, B, Bronsky, E, Gallagher, JCG, Bachman, G, Ebert, G, Resnick, H, Rosenstein, M, Liu, J, Carr, B, Rosenblatt, S, Young, R, Rosen, C, Baker, J, Songcharoen, S, McKenney, J, Zedler, B, Moyer, G, Kerber, I, Gluck, O, Moffett, A, Blank, S, Miller, S, Turner, W, Fearl, J, Wysham, C, Gillie, E, Miller, P, Schwartz, E, Krug, J & Williams, B 2001, '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', Menopause, vol. 8, no. 5, pp. 321-327.
Simon, James A. ; Symons, James P. ; Marcadis, A. ; Nunez, M. ; Guarneri, J. ; Stoukides, J. ; Miaskiewicz, S. L. ; Corm, L. ; Stuccio-White, N. ; Corbin, R. ; Gutierrez, M. ; Weiss, S. ; Portman, D. ; Wolff, R. ; Marx, P. ; Baldwin, D. W. ; Boling, E. ; Silverman, S. ; Wasnich, R. ; Clark, G. ; Emkey, R. ; Greenwald, M. ; Kivitz, A. ; Lnag, R. ; Drinkwater, B. ; Welch, P. ; Aloia, J. ; Bolognese, M. ; Woodson, G. ; Redmond, G. ; Speroff, L. ; Soltes, B. ; Bronsky, E. ; Gallagher, John Christopher G. ; Bachman, G. ; Ebert, G. ; Resnick, H. ; Rosenstein, M. ; Liu, J. ; Carr, B. ; Rosenblatt, S. ; Young, R. ; Rosen, C. ; Baker, J. ; Songcharoen, S. ; McKenney, J. ; Zedler, B. ; Moyer, G. ; Kerber, I. ; Gluck, O. ; Moffett, A. ; Blank, S. ; Miller, S. ; Turner, W. ; Fearl, J. ; Wysham, C. ; Gillie, E. ; Miller, P. ; Schwartz, E. ; Krug, J. ; Williams, B. / 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. In: Menopause. 2001 ; Vol. 8, No. 5. pp. 321-327.
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title = "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",
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.",
author = "Simon, {James A.} and Symons, {James P.} and A. Marcadis and M. Nunez and J. Guarneri and J. Stoukides and Miaskiewicz, {S. L.} and L. Corm and N. Stuccio-White and R. Corbin and M. Gutierrez and S. Weiss and D. Portman and R. Wolff and P. Marx and Baldwin, {D. W.} and E. Boling and S. Silverman and R. Wasnich and G. Clark and R. Emkey and M. Greenwald and A. Kivitz and R. Lnag and B. Drinkwater and P. Welch and J. Aloia and M. Bolognese and G. Woodson and G. Redmond and L. Speroff and B. Soltes and E. Bronsky and Gallagher, {John Christopher G.} and G. Bachman and G. Ebert and H. Resnick and M. Rosenstein and J. Liu and B. Carr and S. Rosenblatt and R. Young and C. Rosen and J. Baker and S. Songcharoen and J. McKenney and B. Zedler and G. Moyer and I. Kerber and O. Gluck and A. Moffett and S. Blank and S. Miller and W. Turner and J. Fearl and C. Wysham and E. Gillie and P. Miller and E. Schwartz and J. Krug and B. Williams",
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TY - JOUR

T1 - Unscheduled bleeding during initiation of continuous combined hormone replacement therapy

T2 - A direct comparison of two combinations of norethindrone acetate and ethinyl estradiol to medroxyprogesterone acetate and conjugated equine estrogens

AU - Simon, James A.

AU - Symons, James P.

AU - Marcadis, A.

AU - Nunez, M.

AU - Guarneri, J.

AU - Stoukides, J.

AU - Miaskiewicz, S. L.

AU - Corm, L.

AU - Stuccio-White, N.

AU - Corbin, R.

AU - Gutierrez, M.

AU - Weiss, S.

AU - Portman, D.

AU - Wolff, R.

AU - Marx, P.

AU - Baldwin, D. W.

AU - Boling, E.

AU - Silverman, S.

AU - Wasnich, R.

AU - Clark, G.

AU - Emkey, R.

AU - Greenwald, M.

AU - Kivitz, A.

AU - Lnag, R.

AU - Drinkwater, B.

AU - Welch, P.

AU - Aloia, J.

AU - Bolognese, M.

AU - Woodson, G.

AU - Redmond, G.

AU - Speroff, L.

AU - Soltes, B.

AU - Bronsky, E.

AU - Gallagher, John Christopher G.

AU - Bachman, G.

AU - Ebert, G.

AU - Resnick, H.

AU - Rosenstein, M.

AU - Liu, J.

AU - Carr, B.

AU - Rosenblatt, S.

AU - Young, R.

AU - Rosen, C.

AU - Baker, J.

AU - Songcharoen, S.

AU - McKenney, J.

AU - Zedler, B.

AU - Moyer, G.

AU - Kerber, I.

AU - Gluck, O.

AU - Moffett, A.

AU - Blank, S.

AU - Miller, S.

AU - Turner, W.

AU - Fearl, J.

AU - Wysham, C.

AU - Gillie, E.

AU - Miller, P.

AU - Schwartz, E.

AU - Krug, J.

AU - Williams, B.

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

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JO - Menopause

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