Frozen Shoulder and Hormone Replacement Therapy

NCT ID: NCT07278323

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-01
• Study Completion Date: 2026-12-31

Brief Summary

The purpose of this study is to determine the effects of hormone replacement therapy (HRT) in addition to standard treatment on frozen shoulder symptoms in women with age-related changes to their menstrual cycle. Frozen shoulder refers to the condition a doctor diagnosed the participant with regarding shoulder pain, stiffness, and progressive loss of range of motion. Age-related menstrual cycle changes, known as perimenopause and/or menopause, refers to a change or stoppage of monthly menstrual cycles. Other symptoms participants may be experiencing include vaginal dryness, hot flashes, or night sweats. Hormone replacement therapy (HRT) refers to medicine with female hormones in it. For this study, HRT will be in the form of a patch that goes on the skin and a daily oral pill. Participants will be randomly assigned to receive either HRT plus standard care, or only standard care. Follow-up tests will be completed at 6 months of treatment to assess participant progress.

Detailed Description

Adhesive capsulitis of the shoulder (ACS), also known as frozen shoulder, affects up to 5% of the population with most cases occurring in peri- and postmenopausal women. This condition is debilitating, negatively impacting quality of life, yet current treatments are insufficient. There are mechanistic studies and biological plausibility to suggest the onset of this condition is associated with hormonal involvement, specifically estrogen. Given hormone replacement therapy (HRT) is widely prescribed to women experiencing menopause-related symptoms, investigators propose using HRT as an adjunct treatment for ACS. The primary objective of this study is to evaluate patient-reported outcomes using the American Shoulder and Elbow Surgeons (ASES) score following treatment with HRT + standard care versus standard care alone. The secondary objective is to determine changes in range of motion (ROM) and functional workspace using both routine clinical metrics and a novel clinical marker-less movement analysis system. Investigators hypothesize that HRT can improve pain scores and ROM limitations in peri- and postmenopausal women who present with ACS. Investigators will recruit 60 women who are peri- or postmenopausal and employ a longitudinal randomized controlled trial to determine the effects of HRT + standard treatment on ACS symptom severity. All participants will receive standard care of physical therapy and a glenohumeral joint steroid injection; the experimental group will also receive HRT. Measures will be repeated after six months of treatments. Within- and between-group changes in pain scores, ROM, and functional workspace will be evaluated using repeated measures ANOVAs with Tukey's multiple comparisons test as indicated by treatment groups. An alpha level of 0.05 will be used to determine statistical significance for all measures. This pilot project will provide critical preliminary data to support future extramural funding applications to government agencies, foundations, and industry partners.

Conditions

Adhesive Capsulitis of the Shoulder; Frozen Shoulder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Hormone Replacement Therapy plus standard care

Participants will be prescribed HRT for 6 months (estrogen patch and oral progestin) in addition to receiving a steroid injection at the shoulder and referral to physical therapy.

Group Type: EXPERIMENTAL

Hormone Replacement Therapy (HRT)

Intervention Type: DRUG

Participants will receive HRT for 6 months consisting of 0.5mg estradiol skin patch and 100mg of oral daily progestin

Corticosteroid and 1%lidocain

Intervention Type: DRUG

Ultrasound-guided glenohumeral joint injections will be performed in clinic by a board-certified fellowship-trained primary care sports medicine physician with expertise performing ultrasound-guided joint injections. Injections will be performed using standard aseptic technique after obtaining informed consent. For local anesthesia, 1 mL of 1% lidocaine will be injected with a 25 gauge 2-inch needle into the skin and subcutaneous tissues. Following this, a 22 gauge 2.5-inch needle will be used to inject a 5 mL combination of 1 mL of 40 mg/mL triamcinolone, 2 mL of 0.2% ropivacaine, and 2 mL of normal saline into the glenohumeral joint.

physical therapy

Intervention Type: BEHAVIORAL

Patients will be referred to physical therapy to complete on their own and will be given an at home program to follow while they wait to see therapists.

Standard Care

Participants will receive standard care for frozen shoulder including a steroid injection at the shoulder and referral to physical therapy

Group Type: ACTIVE_COMPARATOR

Corticosteroid and 1%lidocain

Intervention Type: DRUG

Ultrasound-guided glenohumeral joint injections will be performed in clinic by a board-certified fellowship-trained primary care sports medicine physician with expertise performing ultrasound-guided joint injections. Injections will be performed using standard aseptic technique after obtaining informed consent. For local anesthesia, 1 mL of 1% lidocaine will be injected with a 25 gauge 2-inch needle into the skin and subcutaneous tissues. Following this, a 22 gauge 2.5-inch needle will be used to inject a 5 mL combination of 1 mL of 40 mg/mL triamcinolone, 2 mL of 0.2% ropivacaine, and 2 mL of normal saline into the glenohumeral joint.

physical therapy

Intervention Type: BEHAVIORAL

Patients will be referred to physical therapy to complete on their own and will be given an at home program to follow while they wait to see therapists.

Interventions

Hormone Replacement Therapy (HRT)

Participants will receive HRT for 6 months consisting of 0.5mg estradiol skin patch and 100mg of oral daily progestin

Intervention Type: DRUG

Corticosteroid and 1%lidocain

Ultrasound-guided glenohumeral joint injections will be performed in clinic by a board-certified fellowship-trained primary care sports medicine physician with expertise performing ultrasound-guided joint injections. Injections will be performed using standard aseptic technique after obtaining informed consent. For local anesthesia, 1 mL of 1% lidocaine will be injected with a 25 gauge 2-inch needle into the skin and subcutaneous tissues. Following this, a 22 gauge 2.5-inch needle will be used to inject a 5 mL combination of 1 mL of 40 mg/mL triamcinolone, 2 mL of 0.2% ropivacaine, and 2 mL of normal saline into the glenohumeral joint.

Intervention Type: DRUG

physical therapy

Patients will be referred to physical therapy to complete on their own and will be given an at home program to follow while they wait to see therapists.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Diagnosis of adhesive capsulitis of the shoulder

Exclusion Criteria

• History of hormone sensitive cancer
• Bilateral adhesive capsulitis of the shoulder
• Currently using hormonal treatments including contraceptives

• Minimum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephanie E Wong, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

UCSF Orthopaedic Institute

San Francisco, California, United States

Countries

United States

Central Contacts

Alexa J Chandler, PhD

Role: CONTACT

alexa.chandler@ucsf.edu

(415) 353-2808

Facility Contacts

Alexa J Chandler, PhD

Role: primary

alexa.chandler@ucsf.edu

415-353-2808

Stephanie E Wong, MD

Role: backup

stephanie.wong2@ucsf.edu

(415) 353-2808

References

Klair JS, Yang JD, Abdelmalek MF, Guy CD, Gill RM, Yates K, Unalp-Arida A, Lavine JE, Clark JM, Diehl AM, Suzuki A; Nonalcoholic Steatohepatitis Clinical Research Network. A longer duration of estrogen deficiency increases fibrosis risk among postmenopausal women with nonalcoholic fatty liver disease. Hepatology. 2016 Jul;64(1):85-91. doi: 10.1002/hep.28514. Epub 2016 Apr 5.

Reference Type: BACKGROUND

PMID: 26919573 (View on PubMed)

Hamed-Hamed D, Rodriguez-Perez C, Pruimboom L, Navarro-Ledesma S. Influence of the metabolic and inflammatory profile in patients with frozen shoulder - systematic review and meta-analysis. BMC Musculoskelet Disord. 2025 May 15;26(1):475. doi: 10.1186/s12891-025-08706-9.

Reference Type: BACKGROUND

PMID: 40375116 (View on PubMed)

Kraal T, Lubbers J, van den Bekerom MPJ, Alessie J, van Kooyk Y, Eygendaal D, Koorevaar RCT. The puzzling pathophysiology of frozen shoulders - a scoping review. J Exp Orthop. 2020 Nov 18;7(1):91. doi: 10.1186/s40634-020-00307-w.

Reference Type: BACKGROUND

PMID: 33205235 (View on PubMed)

Cogan CJ, Cevallos N, Freshman RD, Lansdown D, Feeley BT, Zhang AL. Evaluating Utilization Trends in Adhesive Capsulitis of the Shoulder: A Retrospective Cohort Analysis of a Large Database. Orthop J Sports Med. 2022 Jan 25;10(1):23259671211069577. doi: 10.1177/23259671211069577. eCollection 2022 Jan.

Reference Type: BACKGROUND

PMID: 35097146 (View on PubMed)

Other Identifiers

25-44965

Identifier Type: -

Identifier Source: org_study_id