Efficiency and safety of acupuncture for women with premature ovarian insufficiency: study protocol for a randomized controlled trial

doi:10.19852/j.cnki.jtcm.20230214.002

Abstract

Abstract:

Acupuncture has been widely used as an alternative and complementary therapy for premature ovarian insufficiency (POI) in China. However, research to date has not shown that acupuncture is effective for POI compared with hormone replacement therapy (HRT). We will conduct a randomized, controlled, and outcome assessor-blind trial to evaluate the efficacy and safety of acupuncture on POI. Seventy-six patients with POI will be randomly assigned to two groups. The treatment group will receive twenty-eight one-hour sessions of acupuncture treatments, and the control group will receive 12-week HRT. The whole study will consist of a 12-week treatment plan and a 12-week follow-up session. The primary outcome is measured by changes in serum anti-Müllerian hormone and follicle-stimulating hormone (FSH) levels at weeks 12 and 24. Secondary outcome measures include estradiol, luteinizing hormone (LH), LH/FSH ratio, Kupperman index, and menstrual condition. This trial is expected to clarify whether or not acupuncture is effective and safe for POI compared with HRT.

Key words: acupuncture, primary ovarian insufficiency, hormone replacement therapy, randomized controlled trial, study protocols

XU Yani, ZHANG Yutong, HE Weile, DAI Linglin, TANG Ding, WANG Jialing, ZHANG Xufen, CHEN Qin, CHEN Lifang, WANG Zhanglian, ZHAN Mingjie. Efficiency and safety of acupuncture for women with premature ovarian insufficiency: study protocol for a randomized controlled trial[J]. Journal of Traditional Chinese Medicine, 2023, 43(6): 1268-1274.

Figures/Tables 4

References 50.

1.	Eshre guideline: Management of women with premature ovarian insufficiency. Human Reproduction 2016; 31: 926-37. DOI URL
2.	Vujovic S. Aetiology of premature ovarian failure. Menopause Int 2009; 15: 72-5. DOI PMID
3.	Bala R, Singh V, Rajender S, Singh K. Environment, lifestyle, and female infertility. Reprod Sci 2021; 28: 617-38. DOI
4.	Committee opinion no. 698 summary: Hormone therapy in primary ovarian insufficiency. Obstet Gynecol 2017; 129: 963-4. DOI URL
5.	Tsiligiannis S, Panay N, Stevenson JC. Premature ovarian insufficiency and long-term health consequences. Curr Vasc Pharmacol 2019; 17: 604-9. DOI PMID
6.	Benetti-Pinto CL, de Almeida DM, Makuch MY. Quality of life in women with premature ovarian failure. Gynecol Endocrinol 2011; 27: 645-9. DOI PMID
7.	Golezar S, Keshavarz Z, Ramezani Tehrani F, Ebadi A. An exploration of factors affecting the quality of life of women with primary ovarian insufficiency: a qualitative study. BMC Womens Health 2020; 20: 163. DOI PMID
8.	Laven JS. Primary ovarian insufficiency. Semin Reprod Med 2016; 34: 230-4. DOI PMID
9.	De Vos M, Devroey P, Fauser BC. Primary ovarian insufficiency. Lancet 2010; 376: 911-21. DOI PMID
10.	de Villiers TJ, Pines A, Panay N, et al. Updated 2013 international menopause society recommendations on menopausal hormone therapy and preventive strategies for midlife health. Climacteric 2013; 16: 316-37. DOI URL
11.	Baber RJ, Panay N, Fenton A, Group IMSW. 2016 ims recommendations on women's midlife health and menopause hormone therapy. Climacteric 2016; 19: 109-50. DOI PMID
12.	Bachelot A, Nicolas C, Gricourt S, et al. Poor compliance to hormone therapy and decreased bone mineral density in women with premature ovarian insufficiency. PLoS One 2016; 11: e0164638. DOI URL
13.	Fait T. Menopause hormone therapy: latest developments and clinical practice. Drugs in Context 2019; 8: 1-9.
14.	Culliton PD, Kiresuk TJ. Overview of substance abuse acupuncture treatment research. J Altern Complement Med 1996; 2: 149-59; 161-5. DOI URL
15.	Chen YR, Fang YG, Yang JS, Wang F, Wang YY, Yang L. Effect of acupuncture on premature ovarian failure: a pilot study. Evid Based Complement Alternat Med 2014; 2014: 718675.
16.	Zhang J, Huang X, Liu Y, He Y, Yu H. A comparison of the effects of chinese non-pharmaceutical therapies for premature ovarian failure: a prisma-compliant systematic review and network Meta-analysis. Medicine (Baltimore) 2020; 99: e20958. DOI URL
17.	Zhou K, Jiang J, Wu J, Liu Z. Electroacupuncture modulates reproductive hormone levels in patients with primary ovarian insufficiency: results from a prospective observational study. Evid Based Complement Alternat Med 2013; 2013: 657234.
18.	Wang SF, Wan XH, Zhao J, Mao XM, La XL. Comparative effectiveness of acupuncture and hrt interventions for premature ovarian failure: a bayesian Meta-analysis. Int J Clin Exp Med 2017; 10: 15040-50.
19.	Lin J, Wu DH, Jia LY, et al. The treatment of complementary and alternative medicine on premature ovarian failure. Evid Based Complement Alternat Med 2021; 2021: 6677767.
20.	Guven PG, Cayir Y, Borekci B. Effectiveness of acupuncture on pregnancy success rates for women undergoing in vitro fertilization: a randomized controlled trial. Taiwan J Obstet Gynecol 2020; 59: 282-6. DOI URL
21.	Paulus WE, Zhang M, Strehler E, El-Danasouri I, Sterzik K. Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy. Fertil Steril 2002; 77: 721-4. PMID
22.	Villahermosa DI, Santos LG, Nogueira MB, Vilarino FL, Barbosa CP. Influence of acupuncture on the outcomes of in vitro fertilisation when embryo implantation has failed: a prospective randomised controlled clinical trial. Acupunct Med 2013; 31: 157-61. DOI PMID
23.	Wang Y, Li Y, Chen R, Cui X, Yu J, Liu Z. Electroacupuncture for reproductive hormone levels in patients with diminished ovarian reserve: a prospective observational study. Acupunct Med 2016; 34: 386-91. DOI PMID
24.	Dong H, Ludicke F, Comte I, Campana A, Graff P, Bischof P. An exploratory pilot study of acupuncture on the quality of life and reproductive hormone secretion in menopausal women. J Altern Complement Med 2001; 7: 651-8. DOI URL
25.	Zhou J, Qu F, Sang X, Wang X, Nan R. Acupuncture and auricular acupressure in relieving menopausal hot flashes of bilaterally ovariectomized chinese women: a randomized controlled trial. Evid Based Complement Alternat Med 2011; 2011: 713274.
26.	Yi AL, Qin XB, Du ZY, Wang TL, Liu F. Clinical observation on the improvement of serum sex hormone and ovarian function in premature ovarian failure patients with deficiency-cold syndrome by combining wenjing decoction with tiaobu chongren acupuncture and moxibustion. Evid Based Complement Alternat Med 2021; 2021: 3926822.
27.	Pundir J, Charles D, Sabatini L, et al. Overview of systematic reviews of non-pharmacological interventions in women with polycystic ovary syndrome. Hum Reprod Update 2019; 25: 243-56. DOI PMID
28.	Kim DI, Jeong JC, Kim KH, et al. Acupuncture for hot flushes in perimenopausal and postmenopausal women: a randomised, sham-controlled trial. Acupunct Med 2011; 29: 249-56. DOI PMID
29.	Eisenhardt S, Fleckenstein J. Traditional Chinese Medicine valuably augments therapeutic options in the treatment of climacteric syndrome. Arch Gynecol Obstet 2016; 294: 193-200. DOI PMID
30.	Ma S, Wu J, Feng Y, Chen B. Elevated estrogen receptor expression in hypothalamic preoptic area decreased by electroacupuncture in ovariectomized rats. Neurosci Lett 2011; 494: 109-13. DOI PMID
31.	Zhao H, Tian ZZ, Chen BY. Electroacupuncture stimulates hypothalamic aromatization. Brain Res 2005; 1037: 164-70. PMID
32.	Chen BY. Acupuncture normalizes dysfunction of hypothalamic-pituitary-ovarian axis. Acupunct Electrother Res 1997; 22: 97-108. DOI URL
33.	Chang R, Chung PH, Rosenwaks Z. Role of acupuncture in the treatment of female infertility. Fertil Steril 2002; 78: 1149-53. PMID
34.	Bai L, Tian J, Zhong C, et al. Acupuncture modulates temporal neural responses in wide brain networks: Evidence from fmri study. Mol Pain 2010; 6: 73.
35.	Cho ZH, Hwang SC, Wong EK, et al. Neural substrates, experimental evidences and functional hypothesis of acupuncture mechanisms. Acta Neurol Scand 2006; 113: 370-7. DOI PMID
36.	Xu H, Zheng C, He L, et al. Effect of acupuncture on women with poor ovarian response: a study protocol for a multicenter randomized controlled trial. Trials 2020; 21: 775. DOI PMID
37.	Xu H, Hao M, Zheng C, et al. Effect of acupuncture for diminished ovarian reserve: study protocol for a randomized controlled trial. Trials 2021; 22: 720. DOI PMID
38.	Huntley AL, Ernst E. A systematic review of herbal medicinal products for the treatment of menopausal symptoms. Menopause 2003; 10: 465-76. DOI PMID
39.	Zhang L, Li H, Zhang J, et al. A comparison of the efficacy and safety of complementary and alternative therapies for premature ovarian insufficiency: a protocol for network Meta-analysis. Medicine (Baltimore) 2020; 99: e21538. DOI URL
40.	Chan AW, Tetzlaff JM, Altman DG, et al. Spirit 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med 2013; 158: 200-7. DOI URL
41.	MacPherson H, Altman DG, Hammerschlag R, et al. Revised standards for reporting interventions in clinical trials of acupuncture (stricta): extending the consort statement. PLoS Med 2010; 7: e1000261. DOI URL
42.	World Health Organization WHO. Who standard acupuncture point locations in the western pacific region. Geneva: World Health Organization, 2008: 23-219.
43.	Moolhuijsen LME, Visser JA. Anti-mullerian hormone and ovarian reserve: update on assessing ovarian function. J Clin Endocrinol Metab 2020; 105.
44.	Rose MP, Gaines Das RE, Balen AH. Definition and measurement of follicle stimulating hormone. Endocr Rev 2000; 21: 5-22. PMID
45.	Davis SR. The kupperman index undressed. Maturitas 2019; 126: 90-1. DOI PMID
46.	Kupperman HS, Blatt MH, Wiesbader H, Filler W. Comparative clinical evaluation of estrogenic preparations by the menopausal and amenorrheal indices. J Clin Endocrinol Metab 1953; 13: 688-703. DOI URL
47.	Kupperman HS, Wetchler BB, Blatt MH. Contemporary therapy of the menopausal syndrome. J Am Med Assoc 1959; 171: 1627-37. PMID
48.	Fraser IS, Critchley HO, Broder M, Munro MG. The figo recommendations on terminologies and definitions for normal and abnormal uterine bleeding. Semin Reprod Med 2011; 29: 383-90. DOI PMID
49.	Shao STQ. A practical guide to drug clinical trials and gcp. Beijing: Peking University Medical Press, 2010: 35-92.
50.	Toren P, Dor J, Rehavi M, Weizman A. Hypothalamic-pituitary-ovarian axis and mood. Biol Psychiatry 1996; 40: 1051-5. DOI URL

Timepoint	Study period
Timepoint	Enrollment	Baseline Week -4-0	Treatment Week 1-12	Follow-up Week 13-24
Basic information and eligibility:
Informed consent	×
Inclusion/exclusion	×
Medical history	×
Assessments:
AMH		×	×	×
FSH		×	×	×
E₂		×	×	×
LH		×	×	×
LH/FSH ratio		×	×	×
Kupperman index		×	×	×
Menstrual condition		×	×	×
Interventions:
Acupuncture			×
HRT			×
Others:
Adverse events			×	×

Timepoint	Study period
Timepoint	Enrollment	Baseline Week -4-0	Treatment Week 1-12	Follow-up Week 13-24
Basic information and eligibility:
Informed consent	×
Inclusion/exclusion	×
Medical history	×
Assessments:
AMH		×	×	×
FSH		×	×	×
E₂		×	×	×
LH		×	×	×
LH/FSH ratio		×	×	×
Kupperman index		×	×	×
Menstrual condition		×	×	×
Interventions:
Acupuncture			×
HRT			×
Others:
Adverse events			×	×

Menstrual cycle	Drug type	Dose/daily
Day 1-11	Estradiol^aValerate Tablets	1 mg qd
Day 12-21	Estradiol^a+Dydrogesterone Tablets^b	1 mg qd+10 mg bid
Day 22-28	None	None

Menstrual cycle	Drug type	Dose/daily
Day 1-11	Estradiol^aValerate Tablets	1 mg qd
Day 12-21	Estradiol^a+Dydrogesterone Tablets^b	1 mg qd+10 mg bid
Day 22-28	None	None

Clinical dimensions of menstruation and menstrual cycle	Descriptive terms	Normal limits
Menstruation and menstrual cycle		(5-95th percentiles)
Frequency of menses (days)	Frequent	<24
	Normal	24-38
	Infrequent	>38
Regularity of menses, cycle to cycle
Variation over 12 months (days)	Absent	No bleeding
	Regular	Variation±2-20 d
	Irregular	Variation >20 d
Duration of flow (days)	Prolonged	>8.0
	Normal	4.5-8.0
	Shortened	<4.5
Volume of monthly blood loss (mL)	Heavy	>80
	Normal	5-80
	Light	<5

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