Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate

Utian, Wulf H.; Shoupe, Donna; Bachmann, Gloria; Pinkerton, Jo Ann V.; Pickar, James H.

doi:10.1016/s0015-0282(01)01791-5

Cited by 322 publications

(117 citation statements)

References 24 publications

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“…7,9 However, eligibility criteria in previous trials varied widely and doses of ET differed, precluding direct comparison. In contrast to previous ET trial eligibility criteria of 7+ moderate-to-severe VMS/day, 6,22,23 we required fewer VMS (2+/day) and not all VMS were required to be moderate or severe. The mean frequency of VMS at baseline was therefore lower than seen in previous ET trials, 6,22,23 and consistent with the majority of SSRI/SNRI trials targeting VMS.…”

Section: Discussionmentioning

confidence: 76%

“…In contrast to previous ET trial eligibility criteria of 7+ moderate-to-severe VMS/day, 6,22,23 we required fewer VMS (2+/day) and not all VMS were required to be moderate or severe. The mean frequency of VMS at baseline was therefore lower than seen in previous ET trials, 6,22,23 and consistent with the majority of SSRI/SNRI trials targeting VMS. 7,11,12,24,25 Because stringent screening procedures established that participants had stable levels of VMS, 18 we were able to minimize our placebo response relative to those in other trials.…”

Section: Discussionmentioning

confidence: 76%

“…Previous studies have highlighted the dose-dependent efficacy of low-dose oral ET and conjugated equine estradiol (CEE). 6,21–23,28 In a 12-week trial, 17-beta-estradiol 0.5-mg reduced VMS by 65.5% (SD 34.0%) whereas 1.0-mg reduced VMS by 83.2% (SD 25.6%) and placebo reduced VMS by 47.5% (SD 37.2%). 23 Because of endometrial stimulation risks with prolonged us of unopposed ET, 23 our trial was restricted to 8 weeks of treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Studies suggest that low-dose ET preparations diminish VMS, but to a lesser extent than standard doses and with a slower onset of action. 6 …”

Section: Introductionmentioning

confidence: 99%

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Low-Dose Estradiol and the Serotonin-Norepinephrine Reuptake Inhibitor Venlafaxine for Vasomotor Symptoms

et al. 2014

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IMPORTANCE Estrogen therapy is the gold standard treatment for hot flashes and night sweats, but some women are unable or unwilling to use it because of associated risks. The serotonin-norepinephrine reuptake inhibitor venlafaxine hydrochloride is used widely as a nonhormonal treatment. While the clinical impression is that serotonin-norepinephrine reuptake inhibitors are less effective than estrogen, these medications have not been simultaneously evaluated in one clinical trial to date. OBJECTIVE To determine the efficacy and tolerability of low-dose oral 17β-estradiol and low-dose venlafaxine extended release in alleviating vasomotor symptoms (VMS). DESIGN, SETTING, AND PARTICIPANTS In total, 339 perimenopausal and postmenopausal women with at least 2 bothersome VMS per day (mean, 8.1 per day) were recruited from the community to MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) clinical network sites between December 5, 2011, and October 15, 2012. INTERVENTIONS Participants were randomized to double-blind treatment with low-dose oral 17β-estradiol (0.5 mg/d) (n = 97), low-dose venlafaxine hydrochloride extended release (75 mg/d) (n = 96), or placebo (n = 146) for 8 weeks. MAIN OUTCOMES AND MEASURESThe primary outcome was the mean daily frequency of VMS after 8 weeks of treatment. Secondary outcomes were VMS severity, bother, and interference with daily life. Intent-to-treat analyses compared the change in VMS frequency between each active intervention and placebo and between the 2 active treatments.RESULTS Compared with baseline, the mean VMS frequency at week 8 decreased to 3.9 (95% CI, 2.9-4.9) VMS per day (52.9% reduction) in the estradiol group, to 4.4 (95% CI, 3.5-5.3) VMS per day (47.6% reduction) in the venlafaxine group, and to 5.5 (95% CI, 4.7-6.3) VMS per day (28.6% reduction) in the placebo group. Estradiol reduced the frequency of symptoms by 2.3 more per day than placebo (P < .001), and venlafaxine reduced the frequency of symptoms by 1.8 more per day than placebo (P = .005). The results were consistent for VMS severity, bother, and interference. Low-dose estradiol reduced the frequency of symptoms by 0.6 more per day than venlafaxine (P = .09). Treatment satisfaction was highest (70.3%) for estradiol (P < .001 vs placebo), lowest (38.4%) for placebo, and intermediate (51.1%) for venlafaxine (P = .06 vs placebo). Both interventions were well tolerated.CONCLUSIONS AND RELEVANCE Low-dose oral estradiol and venlafaxine are effective treatments for VMS in women during midlife. While the efficacy of low-dose estradiol may be slightly superior to that of venlafaxine, the difference is small and of uncertain clinical relevance.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01418209

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

“…Studies suggest that low-dose ET preparations diminish VMS, but to a lesser extent than standard doses and with a slower onset of action. 6 …”

Section: Introductionmentioning

confidence: 99%

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Low-Dose Estradiol and the Serotonin-Norepinephrine Reuptake Inhibitor Venlafaxine for Vasomotor Symptoms

et al. 2014

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“…The study by the Women’s Health Initiative (WHI), in which a combination of CEE at a dosage of 0.625 mg/day and MPA at a dosage of 2.5 mg/day had been used for HRT, was terminated due to an increased risk of invasive breast cancer and evidence that overall health risks exceed the benefits [4]. On the other hand, it has been proposed that the use of low doses of HRT agents will increase the rates of initiation and long-term continuation of HRT, and the clinical benefits of low-dose estrogen treatment in postmenopausal women have been reported [5, 6, 7, 8, 9, 10]. The establishment of low-dose formulations with potentially fewer side effects is important for enhancing patient acceptance and continuance of HRT.…”

Section: Introductionmentioning

confidence: 99%

Serum Estradiol Concentration as Measured by HPLC-RIA and Bone Mineral Density in Postmenopausal Women during Hormone Replacement Therapy

Uemura¹,

Umino²,

Takikawa³

et al. 2004

Horm Res Paediatr

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Objective: To determine the relationship between the serum estradiol concentration and bone mineral density (BMD) of the lumbar spine in postmenopausal women treated with conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) every other day and every day. Methods: Eighty-four postmenopausal women were randomly treated with hormone replacement therapy (HRT) every other day and every day. Forty-seven women received oral administration of 0.625 mg CEE and 2.5 mg MPA every other day, and 37 women received oral administration of 0.625 mg CEE and 2.5 mg MPA every day. BMD of the lumbar spine at 12 months and serum concentrations of estradiol and estrone at 6 and 12 months after treatment were examined. Results: The estradiol concentration in subjects treated every other day showed a significant (p < 0.001) positive correlation with the percentage change in lumbar BMD, while that in subjects treated every day was not correlated with the percentage change in BMD. The differences between serum estradiol concentrations after 12 months of treatment and initial serum estradiol values in women treated every other day and every day also showed a significant (p < 0.01 and 0.05, respectively) positive correlation with percentage changes in BMD. In women treated every other day, body mass index (BMI) in the subjects in whom BMD did not increase was significantly (p < 0.01) lower than that in the subjects in whom BMD did increase. Conclusions: The serum estradiol concentration in women treated every other day has a strong positive correlation with the percentage change in lumbar BMD, but a higher estradiol concentration may be needed for women in whom BMD did not increase with HRT every other day after due consideration of individual characteristics such as BMI.

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Evaluation of Cardiovascular Event Rates With Hormone Therapy in Healthy, Early Postmenopausal Women

Løbo

2004

Arch Intern Med

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Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate

Cited by 322 publications

References 24 publications

Low-Dose Estradiol and the Serotonin-Norepinephrine Reuptake Inhibitor Venlafaxine for Vasomotor Symptoms

Low-Dose Estradiol and the Serotonin-Norepinephrine Reuptake Inhibitor Venlafaxine for Vasomotor Symptoms

Serum Estradiol Concentration as Measured by HPLC-RIA and Bone Mineral Density in Postmenopausal Women during Hormone Replacement Therapy

Evaluation of Cardiovascular Event Rates With Hormone Therapy in Healthy, Early Postmenopausal Women

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