Review question
This Cochrane review evaluates the effectiveness and safety of bioidentical hormone treatment (BHT) compared to no treatment or non-bioidentical hormone treatment (HT) for vasomotor symptoms experienced during the menopausal transition period.
Background
Various hormone therapies (HT) are available to treat menopausal vasomotor symptoms. Bioidentical hormones are chemically identical to those produced by the human body, and several types are well-tested and available on prescription. Many women have opted for bioidentical hormone therapy (BHT) on the assumption that it would be safer than other forms of HT. However, as it is unclear whether BHT is better or safer than other forms of HT, we evaluated the evidence.
Study characteristics
This review includes 23 randomised controlled trials conducted up to July 2015. These studies included a total of 5779 women who were in the menopausal transition period and suffered from hot flushes. Most of the studies (20/23) included only women with moderate to severe hot flushes. None of the studies reported night sweats as a separate outcome.
Key results
There is low to moderate quality evidence that BHT in various forms and doses is more effective than placebo in decreasing the frequency of moderate to severe hot flushes in women in the menopausal transition period. There was low to moderate quality evidence of higher rates of adverse effects such as headache, vaginal bleeding, breast tenderness and skin reactions in the BHT group. There is some evidence to suggest that higher doses of BHT are associated with more effectiveness but also higher risk of adverse effects. No data are yet available about the safety of BHT with regard to long-term outcomes such as heart attack, stroke and breast cancer. All women with a uterus who are taking any form of estrogen require co-administration of a progestogen, as unopposed estrogen is associated with endometrial hyperplasia.
There is no good evidence of a difference in effectiveness between BHT and CEE, and findings with regard to adverse effects are inconsistent. The quality of the evidence is too low to reach any firm conclusions for this comparison.
Quality of the evidence
The main limitations in the quality of the evidence were study risk of bias (mainly due to poor reporting of methods), imprecision and lack of data suitable for analysis.
There was low to moderate quality evidence that BHT in various forms and doses is more effective than placebo for treating moderate to severe menopausal hot flushes. There was low to moderate quality evidence of higher rates of adverse effects such as headache, vaginal bleeding, breast tenderness and skin reactions in the BHT group. There was some evidence to suggest that higher doses of BHT are associated with greater effectiveness but also with higher risk of adverse effects. Although all the included studies used unopposed estrogen, it is recommended best practice to use progestogen therapy in women with a uterus taking estrogen in order to avoid endometrial hyperplasia, regardless of the source of the estrogen. No data are yet available about the safety of BHT with regard to long-term outcomes such as heart attack, stroke and breast cancer.
There was no good evidence of a difference in effectiveness between BHT and CEE, and findings with regard to adverse effects were inconsistent. The quality of the evidence was too low to reach any firm conclusions.
The main limitations in the quality of the evidence were study risk of bias (mainly due to poor reporting of methods), imprecision and lack of data suitable for analysis.
Various hormone therapies (HT) are available to treat menopausal vasomotor symptoms. Bioidentical hormones are chemically identical to those produced by the human body, and several types are well-tested and available on prescription. Many women have opted for bioidentical hormone therapy (BHT) on the assumption that it is safer than other forms of HT. We evaluated the evidence.
To determine the effectiveness and safety of bioidentical hormones compared to placebo or non-bioidentical hormones for the relief of vasomotor symptoms.
In July 2015 we searched the Cochrane Central Register of Controlled Trials, PubMed, Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), registers of ongoing trials and the reference lists of articles retrieved.
Randomised controlled trials (RCTs) comparing bioidentical hormone therapy (BHT) versus placebo or non-bioidentical hormones.
We used standard methodological procedures expected by the Cochrane Collaboration. Our primary outcome was vasomotor symptoms (hot flushes and night sweats). We evaluated the overall quality of the evidence using Grading of Recommendations Assessment, Development and Evaluation criteria (GRADE).
We included 23 RCTs (5779 participants). Most studies (20/23) included only women with moderate to severe hot flushes. All studies compared unopposed 17 beta-estradiol (beta-estradiol) versus placebo or conjugated equine estrogens (CEE). None of the studies reported night sweats as a separate outcome.
BHT patch versus placebo
Frequency of hot flushes
Four RCTs reported data suitable for analysis. There were fewer hot flushes in the BHT group, with a moderate to large effect size (SMD -0.68, 95% CI -0.83 to -0.53, four RCTs, 793 women, I2 = 67%, low quality evidence). There was moderate heterogeneity, but a consistent direction of effect. Seven RCTs reported data unsuitable for analysis; all reported a benefit in the intervention group.
Symptom intensity
Two RCTs reported analysable data. Measured on a 0-100 visual analogue scale (VAS), hot flush intensity was lower in the BHT group (MD -19.94 points, 95% CI -24.86 to -15.02, two RCTs, 393 women, I2 = 54%, low quality evidence). There was moderate heterogeneity, but a consistent direction of effect.
Adverse effects
Adverse events (such as headache, vaginal bleeding, breast tenderness and skin reactions) were more common in the intervention group (odds ratio (OR) 2.14, 95% CI 1.29 to 3.54, 9 RCTs, 1822 women, I2 = 73%, low quality evidence). There was moderate heterogeneity, but a consistent direction of effect. In one study, five women in the intervention group developed endometrial hyperplasia.
BHT gel versus placebo
Hot flush frequency
Three RCTs reported this outcome, but the data were unsuitable for analysis. All reported a benefit in the BHT group.
Adverse effects
Adverse events were more common in the BHT group (OR 1.41, 95% CI 1.09 to 1.83, 3 RCTs, 1086 women, I2 = 0%, moderate quality evidence).
Oral BHT versus placebo
Hot flush frequency
Two studies reported analysable data. There were fewer hot flushes in the BHT group, with a moderate to large effect size (SMD -0.80, 95% CI -1.03 to -0.57, two RCTs, 356 women, I2 = 14%, low quality evidence).
Adverse effects
There was no evidence of a difference between the groups (OR 1.28, 95% CI 0.84 to 1.96, 3 RCTs, 433 women, I2 = 0%, low quality evidence).
Topical BHT emulsion versus placebo
Hot flush frequency
One study with data unsuitable for analysis reported a benefit in the intervention group.
Adverse effects
There was no evidence of a difference between the groups (OR 1.46, 95% CI 0.80 to 2.66, one RCT, 200 women, low quality evidence).
Intranasal BHT versus placebo
Hot flush frequency
Only one study reported analysable data. There were fewer hot flushes per day in the BHT group (MD -3.04 95% CI -4.05 to -2.03, one study, 458 women, moderate quality evidence)
Adverse effects
Adverse events (such as headache, breast tenderness, arthralgia and nausea) were more common in the intervention group (OR 1.96, 95% CI 1.26 to 3.03, one RCT, 458 women, moderate quality evidence).
Subgroup analyses
Subgroup analyses by dose of BHT suggested that higher doses of BHT may be associated with more effectiveness but also higher risk of adverse effects.
BHT patch versus 0.625 mg CEE
Two RCTs reported this comparison, but the data were unsuitable for analysis.
Hot flush frequency
Both RCTs reported no evidence of a difference between the groups.
Adverse effects
Findings were inconsistent. In one comparison (0.1 mg BHT versus CEE), breast pain and vaginal bleeding were more frequent in the BHT group.
Oral BHT versus 0.625 mg CEE
Hot flush frequency
One study with data unsuitable for analysis reported no evidence of a difference between the groups.
Adverse effects
There was no evidence of a difference between the groups (OR 1.20, 95% CI 0.50 to 2.87, one RCT, 103 women, very low quality evidence).