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From the Department of Obstetrics and Gynaecology, Chinese University of
Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.
Correspondence to Prof Christopher J. Haines, Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Shatin, New Territories, Hong Kong. E-mail cjohnhaines{at}cuhk.edu.hk
Background—Gonadotropin-releasing
hormone agonists (GnRHas) are a group of drugs that with long-term use
induce a pseudomenopausal state in which estrogen production is
suppressed. They are commonly used in the treatment of sex
steroid–dependent conditions. "Add-back" hormone replacement
therapy is used to prevent menopause-like symptoms and bone loss during
GnRHa treatment, but it is also recognized that hypoestrogenism
adversely affects vascular function. The aim of this study was to
examine the effect of GnRHa and add-back therapy on vascular
reactivity. This model serves as a paradigm for the effect of hormone
replacement therapy in postmenopausal women.
Methods and Results—Measurements of
endothelium-dependent and
endothelium-independent vascular reactivity were
compared in 2 groups of women treated with a GnRHa for 6 months. One
group received estrogen/progestogen add-back therapy during the second
3 months of GnRHa treatment. Vascular reactivity was examined by use of
ultrasound measurements of changes in brachial artery diameter.
Endothelium-dependent changes were assessed during
reactive hyperemia, whereas
endothelium-independent changes were measured after the
administration of glyceryl trinitrate sublingual spray. Treatment with
the GnRHa alone had an inhibitory effect on
endothelium-dependent relaxation. However,
endothelium-dependent relaxation significantly improved
in the group receiving add-back therapy (14.6%) compared with the
group treated with GnRHa alone (8.6%) (P<0.01). There
were no significant endothelium-independent changes in
either group.
Conclusions—These results suggest that the administration of
add-back therapy has a protective effect on vascular function in
GnRHa-induced hypoestrogenism. As a model for the menopause, these
results also suggest that the long-term administration of hormone
replacement therapy would result in
endothelium-dependent arterial relaxation,
an observation previously attributed only to the acute administration
of estrogen.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Prospective Randomized Study of the Effect of "Add-Back" Hormone Replacement on Vascular Function During Treatment With Gonadotropin-Releasing Hormone Agonists
Key Words: hormones • vasculature
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