Short report
Evaluation of gabapentin in management of hot flushes in postmenopausal women
Post Reproductive Health, formerly Menopause International 2014, Vol. 20(1) 36–38 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1754045313518527 prh.sagepub.com
Nutan Agarwal, Smita Singh, Alka Kriplani, Neerja Bhatla and Nilanchali Singh
Abstract This study was conducted to assess the efficacy of gabapentin in controlling hot flushes in postmenopausal women. Fifty postmenopausal patients with hot flushes were randomized in two groups, one receiving gabapentin 900 mg daily along with calcium and another group receiving calcium alone. Frequency, duration and severity of hot flushes were noted and a composite score was calculated. There was around an 80% reduction in composite score in the gabapentin group at 3 and 6 months; significantly more than the placebo group. Gabapentin has a two-fold better response than placebo in reducing hot flushes with the relief starting from the first month and maximum effect at 3 months.
Keywords Hot flushes, gabapentin, postmenopausal
Introduction Fifty per cent of postmenopausal women experience vasomotor symptoms.1 Though hormone replacement therapy is effective in reducing hot flushes, due to potential adverse effects an interest in safer non-hormonal therapies has increased. Recent reviews evaluating alternative therapies conclude that there is insufficient evidence regarding their effectiveness.2 Gabapentin has been shown to reduce hot flushes in women with breast cancer, chemical or surgical menopause and in a small sample of women with natural menopause.3–5 There is little emerging evidence about its efficacy but its use in this application is still evolving. No study to date has assessed the efficacy of gabapentin for treatment of hot flushes in Indian women.
Methods This was a pilot study conducted at AIIMS, New Delhi. Ethical clearance was taken from the institutional ethical committee. Fifty women with a natural menopause were recruited after informed consent. Inclusion criteria were women of 45–55 years age, non-menstruating for 1 year, FSH greater than 40 mIU/ml, no pelvic pathology, normal Pap smear and presence of hot flushes. Exclusion criteria were asymptomatic women, abnormal cervical screening results, hormonal treatment within the last six months and renal or liver disorders.
A detailed history was taken regarding symptoms of hot flushes: frequency, severity and duration. Severity of each episode was graded as 1 – mild, 2 – moderate, 3 – severe. Daily hot flushes severity assessment was performed using two parameters: integrated hot flush duration score (frequency duration of each hot flush) and hot flush composite score (frequency severity duration of each hot flush). Patients were randomized into two groups using a computerized method. Group I received gabapentin 900 mg/day (300 mg thrice daily) along with calcium 500 mg while Group II received placebo three times a day with calcium. The participants and interviewer were blinded to the intervention. All women maintained a hot flush diary. They were asked to complete the diary daily for the initial four weeks and thereafter, last week of each month for next five months. A total record for nine weeks was obtained over six months. Follow-ups were performed after one, three and six months of therapy.
Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi Corresponding author: Nutan Agarwal, 55 New Campus, IIT Hauz Khas, New Delhi 110 016, India. Emails: [email protected]; [email protected]
Downloaded from min.sagepub.com at MOUNT ALLISON UNIV on June 18, 2015
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Figure 1. Frequency (a) and duration (b) of hot flushes and Integrated Hot Flush Score (c) and Hot Flush Composite Score (d) in both the groups at one, three and six months’ follow-up. Group I (gabapentin) is represented by blue line and Group II (placebo) by red line. There is significant reduction in all the parameters with gabapentin therapy, with the p values mentioned in the figure.
Results All baseline characteristics including age, duration of menopause, height, weight, BMI, serum FSH, TSH, estradiol and lipid profile were comparable in participants of both groups. The frequency and duration of hot flushes, integrated hot flush duration score and hot flush composite scores in both the groups are shown in Figure 1. Beyond 3 months, only marginal further improvement (2%) was noted in the gabapentin group while no further improvement was seen in control group beyond one month therapy.
Discussion Gabapentin has been evaluated as a non-hormonal treatment option for treatment of hot flushes for the last decade. Our study was the first prospective randomized controlled trial in India. No other study in this country has assessed the efficacy of gabapentin
beyond three months, whereas, in our study, followup was for a full six months. We found a 50–60% reduction in frequency and 30–40% reduction in duration of hot flushes with gabapentin therapy. Other studies have also showed that gabapentin is effective in treatment of hot flushes with significant effects seen after 12 weeks of therapy.3 Some have reported its efficacy in natural menopause.4 Another study has reported 900 mg gabapentin having a better effect in comparison to 300 mg.5 Whilst the degree of efficacy was slightly higher in our study in comparison to other similar studies, the pattern of improvement was similar, in that the improvement noted at one month of therapy was sustained for three months and comparable at three and six months. Estrogen has been reported to reduce hot flushes by 80–95%, but considering some of the possible associated adverse effects, gabapentin can be considered a potential alternative to hormone therapy for management of hot flushes in Indian women.
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38
Post Reproductive Health 20(1)
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflict of Interest None declared.
References 1. McKinlay SM and McKinlay JB. The impact of menopause and social factors on health. Prog Clin Biol Res 1989; 320: 137–161.
2. Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 2006; 295: 2057–2071. 3. Guttuso T Jr, Kurlan R, McDermott MP, et al. Gabapentin’s effects on hot flashes in postmenopausal women: a randomized controlled trial. Obstet Gynecol 2003; 101: 337–345. 4. Butt DA, Lock M, Lewis JE, et al. Gabapentin for the treatment of menopausal hot flashes: a randomized controlled trial. Menopause 2008; 15: 310–318. 5. Pandya KJ, Morrow GR, Roscoe JA, et al. Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial. Lancet 2005; 366: 818–824.
How To Cite Agarwal N, et al. Evaluation of gabapentin in management of hot flushes in postmenopausal women. Post Reproductive Health 2014; 20(1): 36–38.
Downloaded from min.sagepub.com at MOUNT ALLISON UNIV on June 18, 2015
Evaluation of gabapentin in management of hot flushes in postmenopausal women
Post Reproductive Health, formerly Menopause International 2014, Vol. 20(1) 36–38 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1754045313518527 prh.sagepub.com
Nutan Agarwal, Smita Singh, Alka Kriplani, Neerja Bhatla and Nilanchali Singh
Abstract This study was conducted to assess the efficacy of gabapentin in controlling hot flushes in postmenopausal women. Fifty postmenopausal patients with hot flushes were randomized in two groups, one receiving gabapentin 900 mg daily along with calcium and another group receiving calcium alone. Frequency, duration and severity of hot flushes were noted and a composite score was calculated. There was around an 80% reduction in composite score in the gabapentin group at 3 and 6 months; significantly more than the placebo group. Gabapentin has a two-fold better response than placebo in reducing hot flushes with the relief starting from the first month and maximum effect at 3 months.
Keywords Hot flushes, gabapentin, postmenopausal
Introduction Fifty per cent of postmenopausal women experience vasomotor symptoms.1 Though hormone replacement therapy is effective in reducing hot flushes, due to potential adverse effects an interest in safer non-hormonal therapies has increased. Recent reviews evaluating alternative therapies conclude that there is insufficient evidence regarding their effectiveness.2 Gabapentin has been shown to reduce hot flushes in women with breast cancer, chemical or surgical menopause and in a small sample of women with natural menopause.3–5 There is little emerging evidence about its efficacy but its use in this application is still evolving. No study to date has assessed the efficacy of gabapentin for treatment of hot flushes in Indian women.
Methods This was a pilot study conducted at AIIMS, New Delhi. Ethical clearance was taken from the institutional ethical committee. Fifty women with a natural menopause were recruited after informed consent. Inclusion criteria were women of 45–55 years age, non-menstruating for 1 year, FSH greater than 40 mIU/ml, no pelvic pathology, normal Pap smear and presence of hot flushes. Exclusion criteria were asymptomatic women, abnormal cervical screening results, hormonal treatment within the last six months and renal or liver disorders.
A detailed history was taken regarding symptoms of hot flushes: frequency, severity and duration. Severity of each episode was graded as 1 – mild, 2 – moderate, 3 – severe. Daily hot flushes severity assessment was performed using two parameters: integrated hot flush duration score (frequency duration of each hot flush) and hot flush composite score (frequency severity duration of each hot flush). Patients were randomized into two groups using a computerized method. Group I received gabapentin 900 mg/day (300 mg thrice daily) along with calcium 500 mg while Group II received placebo three times a day with calcium. The participants and interviewer were blinded to the intervention. All women maintained a hot flush diary. They were asked to complete the diary daily for the initial four weeks and thereafter, last week of each month for next five months. A total record for nine weeks was obtained over six months. Follow-ups were performed after one, three and six months of therapy.
Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi Corresponding author: Nutan Agarwal, 55 New Campus, IIT Hauz Khas, New Delhi 110 016, India. Emails: [email protected]; [email protected]
Downloaded from min.sagepub.com at MOUNT ALLISON UNIV on June 18, 2015
Agarwal et al.
37
Figure 1. Frequency (a) and duration (b) of hot flushes and Integrated Hot Flush Score (c) and Hot Flush Composite Score (d) in both the groups at one, three and six months’ follow-up. Group I (gabapentin) is represented by blue line and Group II (placebo) by red line. There is significant reduction in all the parameters with gabapentin therapy, with the p values mentioned in the figure.
Results All baseline characteristics including age, duration of menopause, height, weight, BMI, serum FSH, TSH, estradiol and lipid profile were comparable in participants of both groups. The frequency and duration of hot flushes, integrated hot flush duration score and hot flush composite scores in both the groups are shown in Figure 1. Beyond 3 months, only marginal further improvement (2%) was noted in the gabapentin group while no further improvement was seen in control group beyond one month therapy.
Discussion Gabapentin has been evaluated as a non-hormonal treatment option for treatment of hot flushes for the last decade. Our study was the first prospective randomized controlled trial in India. No other study in this country has assessed the efficacy of gabapentin
beyond three months, whereas, in our study, followup was for a full six months. We found a 50–60% reduction in frequency and 30–40% reduction in duration of hot flushes with gabapentin therapy. Other studies have also showed that gabapentin is effective in treatment of hot flushes with significant effects seen after 12 weeks of therapy.3 Some have reported its efficacy in natural menopause.4 Another study has reported 900 mg gabapentin having a better effect in comparison to 300 mg.5 Whilst the degree of efficacy was slightly higher in our study in comparison to other similar studies, the pattern of improvement was similar, in that the improvement noted at one month of therapy was sustained for three months and comparable at three and six months. Estrogen has been reported to reduce hot flushes by 80–95%, but considering some of the possible associated adverse effects, gabapentin can be considered a potential alternative to hormone therapy for management of hot flushes in Indian women.
Downloaded from min.sagepub.com at MOUNT ALLISON UNIV on June 18, 2015
38
Post Reproductive Health 20(1)
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflict of Interest None declared.
References 1. McKinlay SM and McKinlay JB. The impact of menopause and social factors on health. Prog Clin Biol Res 1989; 320: 137–161.
2. Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 2006; 295: 2057–2071. 3. Guttuso T Jr, Kurlan R, McDermott MP, et al. Gabapentin’s effects on hot flashes in postmenopausal women: a randomized controlled trial. Obstet Gynecol 2003; 101: 337–345. 4. Butt DA, Lock M, Lewis JE, et al. Gabapentin for the treatment of menopausal hot flashes: a randomized controlled trial. Menopause 2008; 15: 310–318. 5. Pandya KJ, Morrow GR, Roscoe JA, et al. Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial. Lancet 2005; 366: 818–824.
How To Cite Agarwal N, et al. Evaluation of gabapentin in management of hot flushes in postmenopausal women. Post Reproductive Health 2014; 20(1): 36–38.
Downloaded from min.sagepub.com at MOUNT ALLISON UNIV on June 18, 2015
