Clinical implications of the WHI trial results
Oestrogen deficiency is known to cause urogenital atrophy, dryness and urinary symptoms in menopausal women, and hormone replacement therapy (HRT) has traditionally been used to treat these symptoms. However, recently published results from the Women’s Health Initiative (WHI) trial1 cast doubt on the assumption that reversing urogenital changes with HRT will ameliorate urinary incontinence in menopausal women.
The WHI trial is a US study in women aged between 50 and 79 years. It focuses on strategies for preventing heart disease, breast and colorectal cancer and fracture in postmenopausal women. Results published in 2002 received worldwide attention when they showed an increased risk of coronary heart disease and invasive breast cancer with long-term, combined HRT. The results regarding urinary incontinence were published earlier this year and, although not receiving such broad media coverage, are just as challenging to long-held medical assumptions. They showed that, far from improving urinary incontinence symptoms, HRT actually worsened incontinence in symptomatic women and increased the risk of incontinence in women who were continent before taking HRT.
Urinary incontinence results
The study found that HRT increased the incidence of all types of urinary incontinence at one year in women who were continent at baseline. It also showed that HRT increased the frequency of urinary incontinence in symptomatic women. Incontinent women receiving HRT were also more likely to report that urinary incontinence limited their daily activities and disturbed them, compared to incontinent women receiving placebo.
HRT had the greatest impact on stress incontinence, followed by mixed incontinence.
The incidence of urge incontinence was slightly increased with oestrogen alone but not with combined oestrogen plus progestin. The authors concluded, “Conjugated equine estrogen with or without progestin should not be prescribed for the prevention or relief of [urinary incontinence]."
The role of HRT for genitourinary symptoms
Dr Elizabeth Farrell at the Jean Hailes Foundation in Melbourne has reviewed the trial and its clinical implications and provides a brief report on the organisation’s website2. She says that the study population had many of the risk factors considered to increase the incidence of urinary incontinence; most women had a BMI over 25, were over 60 years, and had more than two children. She says that many urinary incontinence risk factors can be modified with lifestyle improvement, a healthy diet and pelvic floor exercises. She adds, “Oestrogen therapy is still the most appropriate therapy for atrophic symptoms of the genitourinary system. The use of vaginal preparations for these symptoms may be the preferable form of oestrogen.”
The effect of HRT on urinary incontinence
Results from the Women’s Health Initiative trial.
• The WHI trial is a double-blind, placebo-controlled randomised trial in 27,347 postmenopausal women aged between 50 and 79 years. Urinary incontinence symptoms were recorded at baseline and at one year in 23,296 participants.
• Women were randomised to either active treatment or placebo in eitherthe oestrogen plus progestin trial or the oestrogen alone trial. A total of 8,506 participants received oestrogen plus progestin, 5,310 received oestrogen alone, and 13,531 received placebo.
• For women who were continent at baseline:
− HRT increased the incidence of all types of urinary incontinence at one year;
− The relative risk (RR) was highest with stress incontinence (combined HRT RR, 1.87; oestrogen alone RR, 2.15);
− Mixed incontinence was also increased (combined HRT RR, 1.49; oestrogen alone RR, 1.79);
− There was no increased risk of urge incontinence with combined HRT, but an increased risk with oestrogen alone (RR 1.32).
• For women who were incontinent at baseline:
− Frequency worsened (combined HRT RR, 1.38; oestrogen alone RR, 1.47.
− Amount of urinary incontinence worsened (combined HRT RR, 1.20; oestrogen alone RR, 1.59)
Women receiving HRT were more likely to report that incontinence limited their daily activities and bothered or disturbed them.