Does hormone replacement therapy (HRT) cause increased muscle mass or swelling?

Does Hormone Replacement Therapy Cause Increased Muscle Mass or Swelling?

HRT does not cause increased muscle mass in postmenopausal women, but it can cause swelling through fluid retention, breast swelling, and local injection site reactions. 1

Effects on Muscle Mass

HRT does not increase muscle mass or strength in postmenopausal women. The highest quality meta-analysis of 12 randomized controlled trials involving 4,474 women found that HRT users lost only 0.06 kg less lean body mass compared to controls—a difference that was not statistically significant (P = 0.26). 2 This finding held true regardless of:

• Treatment type (estrogen-only vs. estrogen-progesterone combination) 2
• Duration of follow-up (6 months to 6 years) 2
• Time since menopause 2

Multiple individual trials confirm this lack of effect:

• A 48-week randomized controlled trial in 116 postmenopausal women showed no improvement in muscle performance, with the control group (calcium alone) actually showing 4.2% greater leg extensor power than the HRT group 3
• An 11-month weight-bearing exercise study demonstrated that women on HRT gained no additional muscle mass or strength beyond exercise alone 4
• A 6-month double-blind placebo-controlled trial found no difference in hand grip strength or isokinetic knee flexion/extension between HRT and placebo groups 5

Swelling Effects

HRT does cause several types of swelling, though most are mild:

Breast Swelling

• A small number of men receiving testosterone-replacement therapy report breast tenderness and swelling 1
• This is a recognized miscellaneous effect of hormone therapy 1

Fluid Retention

• Fluid retention is uncommon and generally mild 1
• HRT should be used cautiously in patients with congestive heart failure or renal insufficiency due to potential fluid retention 1, 6

Local Injection Site Reactions

• Intramuscular injections of testosterone cause local pain, soreness, bruising, erythema, swelling, nodules, or furuncles 1
• These are common local reactions at injection sites 1

Transdermal Reactions

• Transdermal patches cause skin reactions (erythema, pruritus) in up to 66% of users 1, 6
• Gel preparations cause reactions in only 5% of users 1, 6

Clinical Implications

For patients concerned about muscle mass: HRT should not be prescribed with the expectation of increasing muscle strength or lean body mass. 2 Other interventions such as resistance exercise training should be explored instead. 2

For patients experiencing swelling: Evaluate the type and severity:

• Mild generalized fluid retention is typically manageable but requires caution in those with cardiac or renal disease 1, 6
• Local injection site swelling is expected with intramuscular formulations 1
• Breast swelling, while uncommon, should be monitored 1

Important caveat: The evidence regarding muscle mass comes from postmenopausal women receiving standard HRT doses. The context differs for testosterone replacement in hypogonadal men, where testosterone does increase muscle mass and fat-free mass. 1