Effects of Estrogen Plus Progestin on Gynecologic Cancers and Associated Diagnostic Procedures<SUBTITLE>The Women's Health Initiative Randomized Trial</SUBTITLE>

Abstract

OR YEARS, THERE HAS BEEN CONcern about possible associations of gynecologic malignancies with postmenopausal hormone therapy. The development of endometrial hyperplasia and endometrial cancer with unopposed estrogen is well recognized. To reduce or avoid this complication, progestin has been added, 1-3 although results from randomized trials are extremely limited. These concerns have created a need for reasonable monitoring guidelines to follow-up women who experience vaginal bleeding while taking estrogen plus progestin. The Women's Health Initiative (WHI) trial of estrogen plus progestin provides the first opportunity to examine possible associations of gynecologic malignancies with continuous combined postmenopausal hormone therapy in a large, randomized, double-blind, placebo-controlled setting. The trial was stopped early at the recommendation of the independent data and safety monitoring board on the basis of an increased risk of breast cancer supported by a summary measure of effects indicating risks exceeded

Hormone therapy and ovarian cancer: incidence and survival

“…Likewise, many observational studies have not supported an association [5,11,15,29,31,33]. Two large cohort studies and one randomized controlled trial have suggested an increased risk of 50% in association with EP use [8,13,14]. In comparison, the most recent cohort study, the Million Women study, detected a statistically significant 10% increased risk [7].…”

“…Results from studies conducted in the U.S. [5,11,[13][14][15]31,32], Australia [33], Norway [8], Sweden [29], and U.K [7] have been inconclusive regarding the relationship between EP and ovarian cancer. Overall, we detected no associations with EP use.…”

“…A meta-analysis conducted nearly 10 years ago suggested a 15% increased risk of ovarian cancer associated with ever use of HT [12]. More recently, studies have investigated the type of hormone preparation used [5,7,[13][14][15]. The WHI trial detected an elevated, but not statistically significant, association between estrogen plus progestin therapy (EP) and ovarian cancer [hazard ratio (HR) 1.58, 95% CI 0.77-3.24] [13]; however, during the 5.6-year follow-up period, there were only 32 women diagnosed with ovarian cancer.…”

Frontiers proposal. National Institute on Aging “bench to bedside: estrogen as a case study”

“…The Women's Health Initiative, the parent study for WHIMS (Shumaker et al 2003, was a multicenter, randomized, double-blind, placebo-controlled trial designed to assess effects of a commonly prescribed oral HT on cardiovascular disease, breast cancer, and other health outcomes (Anderson et al 2003;Rossouw et al 2002). Active treatment was with combined HT for women with a uterus [conjugated equine estrogens (CEE) 0.625 mg/day with MPA 2.5 mg/day as a continuous combined preparation; CEE+MPA trial) or with estrogen alone (CEE 0.625 mg/day; CEE-alone trial) for women without a uterus.…”

Hormone replacement therapy in women with spinal cord injury – a survey with literature review

“…2,18 The same studies simultaneously confirmed the two well-known side effects of HRT: increased risk of breast cancer, 2,[19][20][21][22] which rises with the duration of HRT 19 and is substantially greater in oestrogen-progestogen combined HRT; 20 and increased risk of thromboembolism, 2,13,23,24 which seems to be highest in the first year of use. 24 Other reported side effects were increased risk of gall bladder diseases, 13 increased risk of ovarian cancer with continuous use of combined HRT 25 and increased risk of dementia in women aged 65 and older. 26 These new findings have caused much uncertainty among women and their doctors regarding the usage of HRT.…”