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The effect of acupuncture on postmenopausal symptoms and reproductive hormones: a sham controlled clinical trial Didem Sunay,1 Muruvvet Ozdiken,1 Huseyin Arslan,2 Ali Seven,3 Yalcin Aral4 ABSTRACT
system, accompanied with a series of psycho- Background Acupuncture is commonly used to
logical symptoms.1 Oestrogen, either by itself or with progestins is the most consistently gynaecological conditions. In this study, the authors Ministry of Health, Ankara Training and Research Hospital, aimed to investigate whether acupuncture has an However, the Women’s Health Initiative and effect on menopausal symptoms and to explore Million Women Study have identiﬁ ed impor- whether this effect is related to changes in hormone tant risk factors (coronary heart disease, stroke, breast and endometrial cancer) associated with hormone replacement therapy (HRT).3–6 Materials and methods A total of 53
postmenopausal women were alternately assigned Those ﬁ ndings have led to an expanded inter- into two treatment groups: acupuncture (n=27) est in non-hormonal therapies for managing symptoms were assessed using the Menopause Correspondence to
only limited data to support their use. The Rating Scale (MRS). The serum oestradiol, follicular common conclusion in reviews regarding to stimulating hormone (FSH) and luteinising hormone complementary and alternative therapies for (LH) levels were measured at baseline and again the management of menopause related symp- after the fi rst and last sessions. The Student t test toms was that the data were insufﬁ cient to was used for normally distributed data and the recommend any alternative therapy and fur- Wilcoxon signed rank test for not normally ther investigation was still needed.7 8 In the distributed data. The group differences in MRS area of complementary and alternative thera- scores were assessed using non-parametric pies, acupuncture and acupressure treatments are promising, however, the results of pub- Results After treatment, total MRS, and the
lished randomised controlled trials of the somatic and psychological subscale scores were effect of acupuncture on hormone levels and signifi cantly lower in the acupuncture group than the sham group (all p=0.001). The severity of hot fl ushes was found to be signifi cantly decreased after treatment in acupuncture group (p=0.001). In the acupuncture group LH levels were lower and multiple biological responses.16 17 These oestradiol levels were signifi cantly higher than sham responses can occur at or close to the site of group (p=0.046 and p=0.045, respectively) after application, or at a distance, mediated mainly treatment, but there was no difference in FSH by sensory neurons to many structures within the central nervous system. This can lead to Conclusion Acupuncture was effective in reducing
activation of pathways affecting various phys- menopausal complaints when compared to sham iological systems in the brain as well as in the periphery. Stimulation by acupuncture may alternative therapy in the treatment of menopausal also activate the hypothalamus and the pitu- itary gland, resulting in a broad spectrum of systemic effects. Alteration in the secretion of neurotransmitters and neurohormones and INTRODUCTION
changes in the regulation of blood ﬂ ow, both Perimenopause syndrome, referred also as cli- macteric syndrome, results from the changing documented.18of relationship among the hypothalamus, pituitary and ovary during women’s ageing aimed to investigate whether acupuncture has process. Those changes take place ﬁ rst in the an effect on menopausal symptoms and to ovary, then in the hypothalamus and pituitary, explore whether this effect is related to which are reﬂ ected as the functional changes changes in levels of reproductive hormones.
in the endocrinological and central nervous Acupunct Med 2011;29:27–31. doi:10.1136/aim.2010.003285 Original paper
MATERIALS AND METHODS
The secondary outcome measures were hormone lev- After obtaining approval of the local ethical committee, els. Hence, the baseline serum E2 (E2b), FSH (FSHb) and 56 postmenopausal women (50 naturally and six surgi- luteinising hormone (LH; LHb) levels were recorded. cally), who had been referred to the outpatient clinic of These parameters were measured again after the ﬁ rst menopause at Ankara Training and Research Hospital, (E2fs, FSHfs, LHfs) and last sessions (E2ls, FSHls, LHls) to Ankara, Turkey, between October 2009 and December evaluate whether the effect of intervention was cumula- 2009, for follow-up or treatment and who agreed to par- tive. The ﬁ rst session of interventions was applied 2–7 days ticipate were included in this, single-blind, sham-con- trolled study. All participants were informed about the The acupuncture group received traditional Chinese med- study and written consents were received. Participants icine acupuncture twice a week for a total of 10 sessions by were alternately assigned into two treatment groups: acu- a licensed acupuncturist with 6 years experience. Sterile, dis- puncture (n=28) and sham acupuncture (n=28). The age, posable, silver needles with a length of 0.25×25 mm (Wujiang menopausal age, body weight and height of all partici- Jia Chan, Wujiang City, China) were used. The needles were pants were recorded. Body mass index (BMI) was calcu- inserted bilaterally at four acupuncture points (ST36, depth lated by the formula body weight (kg)/height (m2).
1 cun; LI4, 0.5 cun; KI3, 0.2 cun; LR3, 0.3 cun) and also in the The term postmenopausal was deﬁ ned as: 12 months points EX-HN3 at 0.1 cun depth and CV3, 0.5 cun; de qi sen- spontaneous amenorrhea for women who still had a uterus, sation was obtained with manipulation and the needles and serum oestradiol (E2) levels lower than 50 pg/ml and were then left for 20 min without any manual or electrical serum follicular stimulating hormone (FSH) levels higher stimulation. The points were located by the acupuncturist than 40 IU/ml for women who had surgical menopause according to WHO Standard Acupuncture Point Locations and had no uterus. None of the participants had taken HRT Sham acupuncture was performed on the sham group The primary outcome of the study was an assessment twice a week for a total of 10 sessions at the same points of improvement in menopausal symptoms. Hence, meno- by the same acupuncturist. Sham acupuncture needles pausal symptoms were assessed using an 11 item Turkish developed by Streitberger and Kleinhenz22 (Asia Med, version of the Menopause Rating Scale (MRS).19 20 Three Munich, Germany) were used. The blunted needles were aspects were assessed from the menopausal symptoms: inserted by using an O ring and adhesive dressing to avoid somatic (four items), psychological (four items) and uro- penetration to the skin. No other interventions were genital (three items) symptom complexes. A 5-point rating scale allowed the women to describe the perceived sever- In relation to the reproductive hormones, we hypothe- ity of symptoms for each item (severity: 0=no complaints sised that the interventions would be considered effective to 4=very severe symptoms). The composite scores for if FSH and LH levels decreased and oestradiol levels each dimension (subscale) are based on adding the item scores in the respective dimensions. The composite score Data were analysed using SPSS V.12. G-Power V.3.1 (total score) is the sum of the dimension scores.
software was used to evaluate sample size and power of • Received allocated intervention (n=28) • Received allocated intervention (n=27) • Did not receive allocated intervention (n=0) • Did not receive allocated intervention (n=0) Lost to follow-up (unable to contact) (n=1) Discontinued intervention (private reasons) Figure 1 Flow diagram of the progress through the phases of the randomised trail.
Acupunct Med 2011;29:27–31. doi:10.1136/aim.2010.003285 Original paper
the present study. Theoretical power was taken as 0.80 in psychological and urogenital subscale scores (p=0.132, planning the study and the power actually achieved was p=0.066 and p=0.461, respectively). However, all subscale calculated to be 0.71 at the end of the study. Descriptive scores were signiﬁ cantly decreased after therapy in the statistics were expressed as mean±SD for continuously measured variables. Student t test was used for normally When the severity of hot ﬂ ushes in somatic subscale distributed data, and Wilcoxon signed rank test for not was evaluated alone, a signiﬁ cant difference was found normally distributed data for comparisons in dependent between groups, with scores in the acupuncture group sig- groups. The group differences in MRS scores were assessed niﬁ cantly lower than the sham group (p=0.001) after the using non-parametric Mann–Whitney U test. Multivariate last session. For the within group changes in severity of analysis with Bonferroni correction was used posthoc to hot ﬂ ushes no signiﬁ cant difference was observed in the explore changes in FSH levels. A p value of 0.05 was con- sham group (p=0.317), but there was a signiﬁ cant decrease The comparisons of hormone levels (baseline, after the ﬁ rst and last sessions) of groups are shown in table 3. In In the acupuncture group, one patient left the study for the acupuncture group, FSHb levels were higher than personal reasons, in the sham group, one patient did not sham group before treatment (p=0.002), which was con- come to follow-ups and one patient did not meet the inclusion criteria (she had surgical menopause with FSH FSH levels of the acupuncture group were higher than levels lower than 40 IU/ml). Hence, the study was com- the sham group (p=0.009) after the ﬁ rst treatment but not pleted with 53 participants (27 in the study group, 26 in at the end of the course of acupuncture (p=0.659). LH lev- the sham group) analysed (ﬁ gure 1). No adverse effects els in the acupuncture group were signiﬁ cantly lower after were observed in any of the patients.
the ﬁ rst treatment (p=0.036) and also at the end of the The groups were similar in terms of mean age, mean course (p=0.046). Oestrogen levels were signiﬁ cantly menopausal age and mean duration of menopause higher than in the sham group at the end of treatment (p=0.633, p=0.991 and p=0.760, respectively). Mean BMI of the groups were also similar (p=0.186) (table 1).
Considering the changes within the groups before and The MRS scores for the two groups are shown in table 2. after interventions, no signiﬁ cant differences were found When total MRS scores of the groups were compared, no between FSHbs and FSHls, LHb and LHls, E2b and E2ls differences were found between the total scores of the levels in acupuncture and sham groups (p=0.853, p=0.245, groups after the ﬁ rst session (p=0.115), but the total score p=0.138, p=0.043, p=0.904 and p=0.695, respectively).
of the acupuncture group after the last treatment was sig-niﬁ cantly lower than the sham group (p=0.001). The uro- DISCUSSION
genital subscale and hot ﬂ ush severity scores were In the present study, total MRS scores as well as somatic signiﬁ cantly different between groups at baseline, which and psychological (but not urogenital) subscale scores of was considered a random ﬁ nding. Somatic subscale scores acupuncture group were lower than sham group after after the ﬁ rst and last sessions were signiﬁ cantly lower in acupuncture group than the sham group (both p=0.001). The psychological subscale scores after the ﬁ rst session Table 2 Menopause Rating Scale scores of the two groups
were similar in the two groups (p=0.626) whereas the scores after the last session were signiﬁ cantly lower in Acupuncture
acupuncture group than placebo group (p=0.001). Mean±SD
Urogenital subscale scores of the groups were no different (Min–Max)
after the ﬁ rst and last sessions (p=0.447 and p=0.153, When the scores were compared before and after the interventions (within groups), no signiﬁ cant differences were found in sham group in terms of somatic, Psychological Table 1 The mean age, menopausal age, duration of
menopause and mean body mass index (BMI) of the groups Acupuncture
bs, baseline; fs, fi rst session; ls, last session.
Acupunct Med 2011;29:27–31. doi:10.1136/aim.2010.003285 Original paper
Table 3 Hormone levels of groups at baseline and after the fi rst and the last sessions
Follicular stimulating hormone (FSH) FSH bs *Multivariate analysis: no signifi cant effect of time (p=0.464) or group × time interaction (p=0.659).
bs, baseline; fs, fi rst session; ls, last session.
treatment. LH levels were reduced and oestradiol levels symptoms, such as vasomotor symptoms and vaginal or were raised after treatment with acupuncture group, but genital dryness, but also contributed to treatment-related those we believe that those changes in hormone levels are effects, such as bleeding and breast tenderness.26 27 Also not sufﬁ ciently large to explain the changes in symptoms. different results have been reported in studies comparing Most acupuncture studies in this topic have used similar HRT with acupuncture for the treatment of menopausal time frames for acupuncture sessions, but it is not clear symptoms. In some of those, it was reported that symp- whether the length of time chosen for treatment was suf- toms decreased signiﬁ cantly with both treatments,11 28 in ﬁ cient to reﬂ ect acupuncture’s complete effect. Therefore some of them better results with HRT,10 and in others we assessed MRS scores and the hormone levels after the with acupuncture12 13 have been reported.
ﬁ rst session of interventions, to explore whether the effect Among menopausal symptoms, the most prominent of acupuncture was cumulative: we found that the differ- symptom—and the one on which most studies have been ences were greater after the last session than the ﬁ rst conducted—is hot ﬂ ushes. The symptoms are characteris- tic of a heat-dissipation response and consist of sweating It was suggested in 1976 that acupuncture stimulation in on the face, neck and chest, as well as peripheral vasodila- normal ovulatory women may affect endocrine func- tion. Although hot ﬂ ushes clearly accompany oestrogen tions.23 Later, the effect of acupuncture on ovulation induc- withdrawal at menopause, oestrogen alone is not respon- tion was investigated by Yu et al24 who found that ovulation sible since levels do not differ between symptomatic and was induced in ﬁ ve of 11 women with chronic anovula- asymptomatic women. Until recently, it was thought that tory cycles, three of whom conceived. However, different hot ﬂ ushes were triggered by a sudden, downward reset- results have been reported in studies examining the effect ting of the hypothalamic thermoregulatory set-point, since of acupuncture on postmenopausal hormone levels. In there was no evidence of increased core body tempera- some studies, where different acupuncture techniques and ture. Evidence obtained using a rapidly responding different HRT procedures were applied, signiﬁ cantly ingested telemetry pill indicates that the thermoneutral decreased FSH and LH levels and increased oestradiol lev- zone, within which sweating, peripheral vasodilation and els were reported with acupuncture10–12 15 while in some, a shivering do not occur, is virtually non-existent in symp- signiﬁ cant decrease in menopausal symptoms but no tomatic women but normal in asymptomatic women. The change in hormone levels were reported.9 Especially in results suggest that small temperature elevations preced- studies with electroacupuncture, more signiﬁ cant results ing hot ﬂ ushes acting within a reduced thermoneutral were obtained in hormone levels.12 25 Since we observed zone constitute the triggering mechanism. Central sympa- small changes in hormone levels similar to some studies, thetic activation is also elevated in symptomatic women, we speculate that acupuncture might have an effect on which reduces the thermoneutral zone in animal studies. reproductive hormones through some mechanisms that Oestrogen virtually eliminates hot ﬂ ushes but its mecha- we could not explain. It is certain that further studies are nism of action is not known.29 Acupuncture has been sug- gested as an alternative to HRT, based on the fact that In the present study somatic, psychological and urogen- acupuncture increases central β-endorphin activity and ital symptom subscale scores of MRS decreased with acu- therefore may make the thermoregulation more stable puncture therapy. In studies that have investigated the and decrease hot ﬂ ushes and sweating.28 In some studies effect of HRT in treatment of menopausal symptoms, it signiﬁ cant decrease has been reported not in frequency was reported that HRT relieved some menopausal but in severity of hot ﬂ ushes with acupuncture.14 30 Like Acupunct Med 2011;29:27–31. doi:10.1136/aim.2010.003285 Original paper
several other studies, in this study the severity of hot 4. Wassertheil-Smoller S, Hendrix SL, Limacher M, et al; Women’s Health Initiative ﬂ ushes was signiﬁ cantly decreased in the acupuncture Investigators. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women’s Health Initiative: a randomized trial. JAMA 2003;289:2673–84.
group after treatment. However, in the acupuncture group, 5. Beral V; Million Women Study Collaborators. Breast cancer and hormone-replacement signiﬁ cant changes in hormone levels (especially in oestro- therapy in the Million Women Study. Lancet 2003;362:419–27.
gen) were not observed and this suggests that other fac- 6. Beral V, Bull D, Reeves G; Million Women Study Collaborators. Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet tors are activated in the causing hot ﬂ ushes. In another study,9 vasomotor and physical symptoms were found to 7. Nedrow A, Miller J, Walker M, et al. Complementary and alternative therapies for the be improved with acupuncture, although no changes were management of menopause-related symptoms: a systematic evidence review. Arch Intern Med 2006;166:1453–65.
found in sexual symptoms and reproductive hormones.
8. Borrelli F, Ernst E. Alternative and complementary therapies for the menopause. In some studies comparing sham acupuncture to real acupuncture, both forms of acupuncture therapy were 9. Dong H, Lüdicke F, Comte I, et al. An exploratory pilot study of acupuncture on the quality of life and reproductive hormone secretion in menopausal women. effective in the treatment of postmenopausal symp- J Altern Complement Med 2001;7:651–8.
toms.25 28 Recently, Venzke et al31 reported that the sub- 10. Zhou J, Qu F, Sang X, et al. Acupuncture and auricular acupressure in relieving jects obtained beneﬁ t from either form of acupuncture menopausal hot fl ashes of bilaterally ovariectomized Chinese women: a randomized controlled trial. Evid Based Complement Alternat Med 2009 (in press).
treatment and they suggested that non-invasive needling 11. Xia XH, Hu L, Qin ZY, et al. [Multicentral randomized controlled clinical trials about might not be equivalent to no treatment or true placebo treatment of perimenopausal syndrome with electroacupuncture of sanyinjiao (SP 6)]. treatment. However, in the present study, real acupunc- Zhen Ci Yan Jiu 2008;33:262–6.
12. Jin H, Liu TT, Wang R. [Clinical observation on acupuncture at the fi ve-zangshu for ture treatment was superior to sham acupuncture in the treatment of perimenopausal syndrome]. Zhongguo Zhen Jiu 2007;27:572–4.
relief of somatic, and psychological symptoms in post- 13. Qu F, Zhou J, Nan R. Acupuncture for perimenopausal symptoms in women who underwent oophorectomy a comparative study. Forsch Komplementmed 2007;14:25–32.
Despite the importance of the current ﬁ ndings, several 14. Huang MI, Nir Y, Chen B, et al. A randomized controlled pilot study of acupuncture for limitations must be mentioned. First the sample size was postmenopausal hot fl ashes: effect on nocturnal hot fl ashes and sleep quality. very small. Next, as we did not follow-up the patients Fertil Steril 2006;86:700–10.
15. Shen X, Du Y, Yan L, et al. Acupuncture for treatment of climacteric syndrome – a after the treatment we could not know whether the posi- report of 35 cases. J Tradit Chin Med 2005;25:3–6.
tive effects of acupuncture especially on symptoms con- 16. Kim HY, Wang J, Lee I, et al. Electroacupuncture suppresses capsaicin-induced tinue. More reliable results can be obtained in the studies secondary hyperalgesia through an endogenous spinal opioid mechanism. Pain 2009;145:332–40.
with larger sample size and longer follow-up.
17. Arranz L, Guayerbas N, Siboni L, et al. Effect of acupuncture treatment on the immune function impairment found in anxious women. Am J Chin Med 2007;35:35–51.
18. Anonymous. NIH consensus conference. Acupuncture. JAMA 1998;280:1518–24.
19. Bekiroglu N, Konyalioglu R, Ayas S, et al. The comparison of Menopause Rating Scale The current data indicate that acupuncture can be consid- (MRS), Kupperman Index (KI) and Nottingham Health Profi le (NHP) by means of ered as an alternative therapy in the treatment of meno- reliability measures and responsiveness Indexes among menopausal women. Zeynep Kamil Tıp Bülteni 2008;39:11–16.
pausal symptoms particularly in hot ﬂ ushes, in women 20. Potthoff P, Heinemann LA, Schneider HP, et al. [The Menopause Rating Scale (MRS II): methodological standardization in the German population]. Zentralbl Gynakol 2000;122:280–6.
21. World Health Organization Western Pacifi c Region. WHO Standard Acupuncture Point Locations in the Western Pacifi c Region. Manila: WHO, 2008:33–195.
22. Streitberger K, Kleinhenz J. Introducing a placebo needle into acupuncture research. ▶ Evidence is mixed on whether acupuncture is superior to 23. Aso T, Motohashi T, Murata M, et al. The infl uence of acupuncture stimulation on sham in the treatment of hot fl ushes.
plasma levels of LH, FSH, progesterone and estradiol in normally ovulating women. ▶ We compared acupuncture with non-penetrating sham.
Am J Chin Med (Gard City N Y) 1976;4:391–401.
24. Yu J, Zheng HM, Ping SM. [Changes in serum FSH, LH and ovarian follicular growth ▶ Acupuncture was superior for menopause symptom during electroacupuncture for induction of ovulation]. Zhong Xi Yi Jie He Za Zhi 25. Vincent A, Barton DL, Mandrekar JN, et al. Acupuncture for hot fl ashes: a randomized, sham-controlled clinical study. Menopause 2007;14:45–52.
Competing interests None.
26. Barnabei VM, Cochrane BB, Aragaki AK, et al. Menopausal symptoms and Ethics approval This study was conducted with the approval of the local ethical
treatment-related effects of estrogen and progestin in the Women’s Health Initiative. Obstet Gynecol 2005;105:1063–73.
27. Welton AJ, Vickers MR, Kim J, et al. Health related quality of life after combined Provenance and peer review Not commissioned; externally peer reviewed.
hormone replacement therapy: randomised controlled trial. BMJ 2008;337:a1190.
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Statutory Law in the USA: Requiring Silver Nitrate in Eyes of Newborns Copyright 2006 by Ronald B. Standler Table of Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21. History of Prophylaxis of Ophthalmia Neonatorum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3side