The MUSE Study for Menopausal Arthralgia

Recruited participants will be randomized to one of the following arms for 12 weeks: usual clinical care, 17b-Estradiol/progesterone (ET) only, Muscle strengthening exercises (MSE) only, combination of MSE plus ET. All participants will be assessed at Baseline and at 12 weeks.

Estrogen therapy (ET): Participants would apply 17b-estradiol (1.25-2.5 gms/daily) gel transdermally to joints and muscles most affected by arthralgia for 12 weeks. Participants with intact uteri would also be issued micronized Progesterone 200mg tablets to be taken orally for 12 days each month. Medications would be dispensed by the National University Hospital (NUH) pharmacy.

Muscle strengthening exercises (MSE) Exercises would be demonstrated in person by qualified staff physiotherapists. All Participants would be given a standard strength training protocol, with additional tailored exercises targeting their pain conditions, abilities and personal preferences. Exercises would focus on upper and lower body strength generally. Participants would be encouraged to exercise every day, alternating between upper and lower body strength training following the curated exercises. Exercise regimes would be reinforced through weekly reminders, and posts through social media.

MSE plus ET: Participants randomized to combination of would have both treatments administered at the same time within the same intervention period of 12 weeks. In other words, participants would be instructed to do the curated exercises and apply 17b-estradiol (1.25-2.5 gms/daily) gel trans-dermally with micronized progesterone oral tablets.

Usual care: Participants would continue their usual daily routines and come for outcome assessments at baseline and 12 weeks.

Inclusion criteria

• Patients with muscle stiffness and joint discomfort in various sites, including hands, knees, back, hips, and/or shoulders. Patients with pain in only one isolated joint would not be accepted.
• Arthralgia symptoms with onset, or has become worse, over the perimenopausal or early postmenopausal period (within 5 years of the menopause).
• Women should be at the menopause transition, less than or equal to 59 years old at the time of enrollment, or within 5 years of menopause whichever is earlier.

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• Arthralgia for at least 3 months (pain lasting beyond normal injury healing period)
• Community-dwelling and able to ambulate independently.

Exclusion criteria

• History of thrombo-embolic diseases, strokes, ischemic heart disease, dementia or psychiatric disorders, active liver disease or renal impairment, severe hyperlipidemia, gout, thyroid disease, systemic lupus erythematosus, rheumatoid arthritis, or other chronic inflammatory conditions.
• Pregnancy
• Non-adherence to national guidelines for breast cancer screening
• High risk for breast cancer
• Any joint surgery within the last 6 months
• Severe obesity: BMI>35
• Migraine with aura
• Poorly controlled diabetes
• Use of any form of female hormone supplementation within the past 12 weeks.
• High venous thromboembolism risk
• Current cholecystitis, fibroids, or undiagnosed abnormal uterine bleeding.
• Current smoker.
• History of endometrial, ovarian, peritoneal, cervical, breast or endocrine-dependent cancers.
• Receiving treatment for any form of cancer.
• History of fragility bone fractures within the 2 years.
• Any other cognitive, musculoskeletal, neurological, and cardiorespiratory condition affecting one's ability to participate in the study.