期刊
CLIMACTERIC
卷 18, 期 2, 页码 121-134出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/13697137.2014.947254
关键词
VAGINAL; ESTROGEN; ABSORPTION; MENOPAUSAL; SYSTEMIC; SIDE-EFFECTS
Context The use of systemic estrogens for the treatment of menopausal symptoms has declined by approximately 80% following the initial publication of the Women's Health Initiative in 2002. Current attention focuses on vaginal estrogen as a local therapeutic means to achieve control of symptoms due to vulvovaginal atrophy without increasing plasma estradiol levels. A key issue is whether or not vaginally administered estrogens are absorbed and produce systemic effects. Evidence acquisition Medline and PubMed were searched for relevant English-language articles using pertinent key words. The bibliographies of the pertinent articles were then read to identify further relevant articles. Evidence synthesis Several confounding factors influenced the data analysis including: (1) estradiol assay sensitivity and specificity; (2) acute versus chronic absorption; (3) delivery systems, doses, timing, and formulation; and (4) effect of atrophic versus mature vaginal mucosa on absorption. Each preparation was associated with acute estradiol absorption with peaks at approximately 8 h and return to baseline at 12 h. Low-dose vaginal estrogen, arbitrarily defined as the 7.5-mu g vaginal ring and 10-mu g tablet, increased plasma estradiol levels during chronic administration but not above the normal range of <= 20 pg/ml. Surprisingly, these increments were associated with systemic effects to lower plasma levels of low density lipoprotein cholesterol and bone resorption rates. Intermediate doses (i.e. 25 mu g estradiol or 0.3 mg conjugated equine estrogen) resulted in plasma estradiol levels approaching or exceeding 20 pg/ml. The higher doses (50-2000 mu g estradiol or 0.625-2.5 mg conjugated equine estrogen) resulted in premenopausal levels of estrogen. Conclusions Low-dose vaginal estrogen appears to be an effective strategy for managing women whose symptoms result from vulvovaginal atrophy. These regimens limit but do not completely eliminate systemic absorption. Low-doses regimens should be preferred clinically to intermediate-or high-dose methods.
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