Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Women's Health
Published in: BMC Women's Health 1/2016

Open Access 01-12-2016 | Study protocol

Does menopausal hormone therapy (MHT), exercise or a combination of both, improve pain and function in post-menopausal women with greater trochanteric pain syndrome (GTPS)? A randomised controlled trial

Authors: Charlotte Ganderton, Adam Semciw, Jill Cook, Tania Pizzari

Published in: BMC Women's Health | Issue 1/2016

Login to get access

Abstract

Background

Greater trochanteric pain syndrome (GTPS) is pathology in the gluteus medius and minimus tendons and trochanteric bursa that causes debilitating tendon pain and dysfunction, particularly in post-menopausal women. Limited evidence in clinical studies suggests hormone changes after menopause may have a negative effect on tendon. This protocol describes a randomised controlled trial comparing the effectiveness of menopausal hormone therapy (MHT) and exercise therapy in reducing pain and dysfunction associated with GTPS in post-menopausal women.

Method

One hundred and sixteen post-menopausal women will be recruited and randomised to receive one of two exercise programs (sham or targeted intervention exercise) and transdermal creams (MHT cream containing oestradiol 50mcg and norethisterone acetate 140mcg or placebo cream). Interventions will be 12-weeks in duration and outcomes will be examined at baseline, 12-weeks and 52-weeks. The primary outcome measure will be the VISA-G questionnaire and secondary outcomes measures will include three hip pain and function questionnaires (Hip dysfunction and Osteoarthritis Outcome Score, Oxford Hip Score, Lateral Hip Pain questionnaire), a global change in symptom questionnaire (using a 15-point Likert scale) and a quality of life measure (AQoL-8D questionnaire). Data will be analysed using the intention to treat principle.

Discussion

This study is the first randomised controlled trial to compare the effectiveness of menopausal hormone therapy therapy alone, and with the combination of exercise therapy, to treat pain and dysfunction associated with GTPS. This study has been pragmatically designed to ensure that the interventions in this study can be integrated into policy and clinical practice if found to be effective in the treatment of GTPS in post-menopausal women. If successful, there is potential for this treatment regimen to be explored in future studies of other persistent tendon conditions in the post-menopausal population.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12614001157​662 Registered 31 October 2014.
Appendix
Available only for authorised users
Literature
1.
Gordon E: Trochanteric bursitis and tendinitis. Clinical Orthopaedics and Related Research 1961 20:193–202.
2.
Lievense A, Bierma-Zeinstra S, Schouten B, Bohnen A, Verhaar J, Koes B: Prognosis of trochanteric pain in primary care. British Journal of General Practice 2005, 55(512):199–204.
3.
Segal NA, Felson DT, Torner JC, Zhu Y, Curtis JR, Niu J, Nevitt MC: Greater Trochanteric Pain Syndrome: Epidemiology and Associated Factors. Arch Phys Med Rehabil 2007, 88(8):988–992.
4.
Demant AW, Kocovic L, Henschkowski J, Siebenrock KA, Ferrari P, Steinbach LS, Anderson SE: Hip pain in renal transplant recipients: symptomatic gluteus minimus and gluteus medius tendon abnormality as an alternative MRI diagnosis to avascular necrosis. AJR American journal of roentgenology 2007, 188(2):515–519.
5.
Kountouris A, Cook J: Rehabilitation of Achilles and patellar tendinopathies. Best Practice and Research Clinical Rheumatology 2007, 21(2):295–316.
6.
Cook JL, Bass SL, Black JE: Hormone therapy is associated with smaller Achilles tendon diameter in active post-menopausal women. Scandinavian Journal of Medicine and Science in Sports 2007, 17(2):128–132.
7.
Gibbon WW, Cooper JR, Radcliffe GS: Distribution of sonographically detected tendon abnormalities in patients with a clinical diagnosis of chronic Achilles tendinosis. Journal of Clinical Ultrasound 2000, 28(2):61–66.
8.
Moalli PA, Talarico LC, Sung VW, Klingensmith WL, Shand SH, Meyn LA, Watkins SC: Impact of menopause on collagen subtypes in the arcus tendineous fasciae pelvis. American Journal of Obstetrics and Gynecology 2004, 190(3):620–627.
9.
Maffulli N, Waterston SW, Squair J, Reaper J, Douglas S: Changing Incidence of Achilles Tendon Rupture in Scotland: A 15-Year Study. Clinical Journal of Sport Medicine 1999, 9(3):157–160.
10.
Greising SM, Baltgalvis KA, Lowe DA, Warren GL: Hormone therapy and skeletal muscle strength: a meta-analysis. The journals of gerontology Series A, Biological sciences and medical sciences 2009, 64(10):1071–1081.
11.
Calleja-Agius J, Brincat MP: Hormone replacement therapy post Women's Health Initiative study: where do we stand? Current Opinion in Obstetrics and Gynecology 2008, 20(6):513–518.
12.
Wells G, Cranney A, Tugwell P, Shea B, Guyatt G, Peterson J, Zytaruk N, Robinson V, Henry D, O'Connell D et al: Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Endocrine Reviews 2002, 23(4):529.
13.
Brincat M, Kabalan S, Studd JW, Moniz CF, de Trafford J, Montgomery J: A study of the decrease of skin collagen content, skin thickness, and bone mass in the postmenopausal woman. Obstetrics and Gynecology 1987, 70(6):840–845.
14.
Frizziero A, Vittadini F, Gasparre G, Masiero S: Impact of oestrogen deficiency and aging on tendon: concise review. Muscles, ligaments and tendons journal 2014, 4(3):324–328.
15.
Torricelli P, Veronesi F, Pagani S, Maffulli N, Masiero S, Frizziero A, Fini M: In vitro tenocyte metabolism in aging and oestrogen deficiency. Age (Dordrecht, Netherlands) 2013, 35(6):2125–2136.
16.
Veronesi F, Della Bella E, Torricelli P, Pagani S, Fini M: Effect of adipose-derived mesenchymal stromal cells on tendon healing in aging and estrogen deficiency: An in vitro co-culture model. Cytotherapy 2015, 17(11):1536–1544.
17.
Hansen M, Kongsgaard M, Holm L, Skovgaard D, Magnusson SP, Qvortrup K, Larsen JO, Aagaard P, Dahl M, Serup A et al: Effect of estrogen on tendon collagen synthesis, tendon structural characteristics, and biomechanical properties in postmenopausal women. Journal of Applied Physiology 2009, 106(4):1385–1393.
18.
Pingel J, Langberg H, Skovgård D, Koskinen S, Flyvbjerg A, Frystyk J, Kæjer M, Hansen M: Effects of transdermal estrogen on collagen turnover at rest and in response to exercise in postmenopausal women. Journal of Applied Physiology 2012, 113(4):1040–1047.
19.
Bryant AL, Clark RA, Bartold S, Murphy A, Bennell KL, Hohmann E, Marshall-Gradisnik S, Payne C, Crossley KM: Effects of estrogen on the mechanical behavior of the human Achilles tendon in vivo. Journal of Applied Physiology 2008, 105(4):1035–1043.
20.
Liu SH, Al-Shaikh RA, Panossian V, Finerman GA, Lane JM: Estrogen affects the cellular metabolism of the anterior cruciate ligament. A potential explanation for female athletic injury. The American Journal of Sports Medicine 1997, 25(5):704–709.
21.
Yu WD, Liu SH, Hatch JD, Panossian V, Finerman GA: Effect of estrogen on cellular metabolism of the human anterior cruciate ligament. Clinical Orthopaedics and Related Research 1999, 366(366):229–238.
22.
Hansen M, Miller BF, Holm L, Doessing S, Petersen SG, Skovgaard D, Frystyk J, Flyvbjerg A, Koskinen S, Pingel J et al: Effect of administration of oral contraceptives in vivo on collagen synthesis in tendon and muscle connective tissue in young women. Journal of Applied Physiology 2009, 106(4):1435–1443.
23.
Dehghan F, Muniandy S, Yusof A, Salleh N: Sex-steroid regulation of relaxin receptor isoforms (RXFP1 & RXFP2) expression in the patellar tendon and lateral collateral ligament of female WKY rats. International journal of medical sciences 2014, 11(2):180–191.
24.
Finni T, Kovanen V, Ronkainen PH, Pollanen E, Bashford GR, Kaprio J, Alen M, Kujala UM, Sipila S: Combination of hormone replacement therapy and high physical activity is associated with differences in Achilles tendon size in monozygotic female twin pairs. Journal of Applied Physiology 2009, 106(4):1332–1337.
25.
Hansen M, Couppe C, Hansen CSE, Skovgaard D, Kovanen V, Larsen JO, Aagaard P, Magnusson SP, Kjaer M: Impact of oral contraceptive use and menstrual phases on patellar tendon morphology, biochemical composition, and biomechanical properties in female athletes. Journal of Applied Physiology 2013, 114(8):998–1008.
26.
Hansen M, Koskinen SO, Petersen SG, Doessing S, Frystyk J, Flyvbjerg A, Westh E, Magnusson SP, Kjaer M, Langberg H: Ethinyl oestradiol administration in women suppresses synthesis of collagen in tendon in response to exercise. J Physiol (Lond) 2008, 586(Pt 12):3005–3016.
27.
Ohberg L, Lorentzon R, Alfredson H: Eccentric training in patients with chronic Achilles tendinosis: normalised tendon structure and decreased thickness at follow up. British journal of sports medicine 2004, 38(1):8–11.
28.
Young MA, Cook JL, Purdam CR, Kiss ZS, Alfredson H: Eccentric decline squat protocol offers superior results at 12 months compared with traditional eccentric protocol for patellar tendinopathy in volleyball players. British journal of sports medicine 2005, 39(2):102–105.
29.
Alfredson H, Pietilä T, Jonsson P, Lorentzon R: Heavy-load eccentric calf muscle training for the treatment of chronic Achilles tendinosis. The American journal of sports medicine 1998, 26(3):360–366.
30.
Jonsson P, Alfredson H: Superior results with eccentric compared to concentric quadriceps training in patients with jumper's knee: a prospective randomised study. British journal of sports medicine 2005, 39(11):847–850.
31.
Silbernagel KG, Thomeé R, Thomeé P, Karlsson J: Eccentric overload training for patients with chronic Achilles tendon pain--a randomised controlled study with reliability testing of the evaluation methods. Scandinavian journal of medicine & science in sports 2001, 11(4):197–206.
32.
Purdam CR, Jonsson P, Alfredson H, Lorentzon R, Cook JL, Khan KM: A pilot study of the eccentric decline squat in the management of painful chronic patellar tendinopathy. British journal of sports medicine 2004, 38(4):395–397.
33.
Alfredson H, Cook J, Institutionen för kirurgisk och perioperativ v, Medicinska f, Umeå u, Idrottsmedicin: A treatment algorithm for managing Achilles tendinopathy: new treatment options. British journal of sports medicine 2007, 41(4):211–216.
34.
Rudavsky A, Cook J: Physiotherapy management of patellar tendinopathy (jumper's knee). Journal of physiotherapy 2014, 60(3):122-129.
35.
Del Buono A, Papalia R, Khanduja V, Denaro V, Maffulli N: Management of the greater trochanteric pain syndrome: a systematic review. British medical bulletin 2012, 102(1):115–131.
36.
Cook JL, Purdam CR: Is tendon pathology a continuum? A pathology model to explain the clinical presentation of load-induced tendinopathy. British Journal of Sports Medicine 2009, 43(6):409–416.
37.
Rompe JD, Segal NA, Cacchio A, Furia JP, Morral A, Maffulli N: Home Training, Local Corticosteroid Injection, or Radial Shock Wave Therapy for Greater Trochanter Pain Syndrome. Am J Sports Med 2009, 37(10):1981–1990.
38.
Coombes BK, Bisset L, Brooks P, Khan A, Vicenzino B: Effect of corticosteroid injection, physiotherapy, or both on clinical outcomes in patients with unilateral lateral epicondylalgia: a randomized controlled trial. Journal of the American Medical Association 2013, 309(5):461–469.
39.
Coombes BK, Bisset L, Vicenzino B: Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: a systematic review of randomised controlled trials. The Lancet 2010, 376(9754):1751–1767.
40.
Bisset L, Beller E, Jull G, Brooks P, Darnell R, Vicenzino B: Mobilisation with movement and exercise, corticosteroid injection, or wait and see for tennis elbow: randomised trial. BMJ: British Medical Journal 2006, 333(7575):939–941.
41.
Chan A-W, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jeric K, Hróbjartsson A, Mann H, Dickersin K, Berlin J et al: SPIRIT 2013 Statement: Defining standard protocol items for clinical trials. Annals of Internal Medicine 2013, 158:200–207.
42.
Lequesne M, Mathieu P, Vuillemin-Bodaghi V, Bard H, Djian P: Gluteal tendinopathy in refractory greater trochanter pain syndrome: diagnostic value of two clinical tests. Arthritis and rheumatology 2008, 59(2):241-246.
43.
Dennison J, Beverland DE: An audit of trochanteric bursitis in total hip arthroplasty and recommendations for treatment. Orthopaedic Nursing 2002, 6(1):5–8.
44.
Mitchell B, McCrory P, Brukner P, O'Donnell J, Colson E, Howells R: Hip Joint Pathology: Clinical Presentation and Correlation Between Magnetic Resonance Arthrography, Ultrasound, and Arthroscopic Findings in 25 Consecutive Cases. Clinical Journal of Sport Medicine 2003, 13(3):152–156.
45.
Carlin J, Doyle L: Statistics for Clinicians. Journal of Paediatric Child Health 2002, 38:300–304.
46.
Fergusson D, Glass KC, Waring D, Shapiro S: Turning a blind eye: the success of blinding reported in a random sample of randomised, placebo controlled trials. BMJ (Clinical research ed) 2004, 328(7437):432–434.
47.
Main CJ, Sowden G, Hill JC, Watson PJ, Hay EM: Integrating physical and psychological approaches to treatment in low back pain: The development and content of the STarT Back trial's 'high-risk' intervention (StarT Back; ISRCTN 37113406). Physiotherapy 2012, 98(2):110–117.
48.
Satyendra L, Byl N: Effectiveness of physical therapy for Achilles tendinopathy: An evidence based review of eccentric exercises. Isokinetics and Exercise in Sport Science 2006, 14(1):71–80.
49.
Grigg NL, Wearing SC, Smeathers JE: Eccentric calf muscle exercise produces a greater acute reduction in Achilles tendon thickness than concentric exercise. British Journal of Sports Medicine 2009, 43(4):280–283.
50.
Ark Mv, Cook J, Docking S, Zwerver J, Gaida J, Akker-Scheek Ivd, Rio E: 14 Exercise programs to decrease pain in athletes with patellar tendinopathy inseason: a rct. British Journal of Sports Medicine 2014, 48(18):Suppl 2 A9(2).
51.
Naugle KM, Fillingim RB, Riley rJL: A meta-analytic review of the hypoalgesic effects of exercise. The journal of pain : official journal of the American Pain Society 2012, 13(12):1139–1150.
52.
Guyatt GH, Pugsley SO, Sullivan MJ, Thompson PJ, Berman L, Jones NL, Fallen EL, Taylor DW: Effect of encouragement on walking test performance. Thorax 1984, 39(11):818–822.
53.
Schulz KF, Altman DG, Moher D, for the CG, Grp C, Group C: CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ (Clinical research ed) 2010, 340(7748):c332–702.
54.
Hertoghe T: The hormone handbook. The keys to safe hormone therapies: how to do it and how to solve therapy problems., 2nd edn. Luxembourg: International Medical Books; 2010.
55.
Balfour JA, Heel RC: Transdermal Estradiol. Drugs 2012, 40(4):561–582.
56.
57.
58.
MIMS Online: Estalis Continuous oestradiol/norethisterone acetate (NETA). In., vol. 2014. Australia: MIMS Australia; 2014.
59.
Furness S, Roberts H, Marjoribanks J, Lethaby A: Hormone therapy in postmenopausal women and risk of endometrial hyperplasia. Cochrane Database of Systematic Reviews 2012, 8(8):CD000402.
60.
Fearon AM, Ganderton C, Scarvell JM, Smith PN, Neeman T, Nash C, Cook JL: Development and validation of a VISA tendinopathy questionnaire for greater trochanteric pain syndrome, the VISA-G. Manual therapy 2015(0).
61.
HARRIS WH: Traumatic Arthritis of the Hip after Dislocation and Acetabular Fractures: Treatment by Mold Arthroplasty, vol. 51; 1969.
62.
Fairbank JC, Pynsent PB: The Oswestry Disability Index. Spine 2000, 25(22):2940–2952.
63.
Dawson J, Fitzpatrick R, Carr A, Murray D: Questionnaire on the perceptions of patients about total hip replacement. The Journal of bone and joint surgery British volume 1996, 78(2):185–190.
64.
Klässbo M, Larsson E, Mannevik E: Hip disability and osteoarthritis outcome scoreAn extension of the Western Ontario and McMaster Universities Osteoarthritis Index. Scandinavian Journal of Rheumatology 2003, 32(1):46–51.
65.
Vo T, Rice ASC, Dworkin RH: Non-steroidal anti-inflammatory drugs for neuropathic pain: how do we explain continued widespread use? Pain 2009, 143(3):169–171.
66.
Canonico M, Emmerich J, Scarabin P-Y, Oger E, Plu-Bureau G, Conard J, Meyer G, Lévesque H, Trillot N, Barrellier M-T et al: Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation 2007, 115(7):840–845.
67.
Laliberte F, Dea K, Duh MS, Kahler KH, Rolli M, Lefebvre P: Does Route of Administration for Estrogen Hormone Therapy Impact Risk of Venous Thromboembolism: Estradiol Transdermal System vs. Oral Estrogen-Only Hormone Therapy. Pharmacoepidemiology and Drug Safety 2011, 20:S181–S182.
68.
Shoupe D: Individualizing hormone therapy to minimize risk: accurate assessment of risks and benefits. In., vol. 7. England: Future Medicine Ltd; 2011: 475–485.
69.
George S, Delitto A: Clinical Examination Variables Discriminate Among Treatment-Based Classification Groups: A Study of Construct Validity in Patients With Acute Low Back Pain. Physical Therapy 2005, 85(4):306–314.
70.
Fearon AM, Scarvell JM, Neeman T, Cook JL, Cormick W, Smith PN: Greater trochanteric pain syndrome: defining the clinical syndrome. British journal of sports medicine 2013, 47(10):649–653.
71.
Bunker TD, Esler CN, Leach WJ: Rotator-cuff tear of the hip. The Journal of bone and joint surgery British volume 1997, 79(4):618-620.
72.
Kagan nA: Rotator cuff tears of the hip. Clinical orthopaedics and related research 1999, 368(368):135–140.
73.
Lequesne M, Djian P, Vuillemin V, Mathieu P: Prospective study of refractory greater trochanter pain syndrome. MRI findings of gluteal tendon tears seen at surgery. Clinical and MRI results of tendon repair. Joint Bone Spine 2008, 75(4):458–464.
74.
Robertson WJ, Gardner MJ, Barker JU, Boraiah S, Lorich DG, Kelly BT: Anatomy and dimensions of the gluteus medius tendon insertion. Arthroscopy 2008, 24(2):130–136.
75.
Levangie PK, Norkin CC: Joint structure and function: a comprehensive analysis, 3rd edn. Philadelphia: F.A. Davis Company; 2011.
76.
Grimaldi A: Assessing lateral stability of the hip and pelvis. Manual therapy 2011, 16(1):26–32.
77.
Spear IM, Lipscomb PR: Noninfectious trochanteric bursitis and peritendinitis. Surgical Clinics of North America 1952:1217–1224.
78.
Karpinski MR, Piggott H: Greater trochanteric pain syndrome. A report of 15 cases. J Bone Joint Surg Br 1985, 67(5):762–763.
79.
Tortolani PJ, Carbone JJ, Quartararo LG: Greater trochanteric pain syndrome in patients referred to orthopedic spine specialists. Spine J 2002, 2(4):251–254.
80.
Soslowsky LJ, Thomopoulos S, Tun S, Flanagan CL, Keefer CC, Mastaw J, Carpenter JE: Overuse activity injures the supraspinatus tendon in an animal model: A histologic and biomechanical study. Journal of Shoulder and Elbow Surgery 2000, 9(2):79–84.
81.
Ingber D, Folkman J: Tension and compression as basic determinants of cell form and function: utilization of a cellular tensegrity mechanism. San Diego, CA: Academic Press; 1989.
82.
Cook JL, Purdam C: Rehabilitation of lower limb tendinopathies. Clinical Journal of Sport Medicine 2003, 22(4):777–789.
83.
Sciascia A, Cromwell R: Kinetic chain rehabilitation: a theoretical framework. Rehabilitation research and practice 2012, 2012:853037–853039.
84.
Silbernagel KG, Gustavsson A, Thomeé R, Karlsson J, Institutionen för kliniska vetenskaper sfaboo, Göteborgs u, Institute of Clinical Sciences SfAB, Orthopaedics, Sahlgrenska A, University of G et al: Evaluation of lower leg function in patients with Achilles tendinopathy. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA 2006, 14(11):1207–1217.
85.
Wells P, Anderson D, al. BJe: Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet Oncology 1997 350(9094):1795–1798.
Metadata
Title
Does menopausal hormone therapy (MHT), exercise or a combination of both, improve pain and function in post-menopausal women with greater trochanteric pain syndrome (GTPS)? A randomised controlled trial
Authors
Charlotte Ganderton
Adam Semciw
Jill Cook
Tania Pizzari
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Women's Health / Issue 1/2016
Electronic ISSN: 1472-6874
DOI
https://doi.org/10.1186/s12905-016-0311-9

Other articles of this Issue 1/2016

BMC Women's Health 1/2016 Go to the issue

Research article

The association between subjective assessment of menstrual bleeding and measures of iron deficiency anemia in premenopausal African-American women: a cross-sectional study

Research article

Prenatal care and childbirth assistance in Amazonian women before and after the Pacific Highway Construction (2003–2011): a cross-sectional study

Research article

The conduct of maternal and perinatal death reviews in Oyam District, Uganda: a descriptive cross-sectional study

Research article

Tailoring communications to the evolving needs of patients throughout the cancer care trajectory: a qualitative exploration with breast cancer patients

Research article

Factors related to HPV vaccine uptake and 3-dose completion among women in a low vaccination region of the USA: an observational study

Research article

Vision-related quality of life and psychological status in Chinese women with Sjogren’s syndrome dry eye: a case-control study