What is the approach to hormone replacement therapy (HRT) in men and women?

Approach to Hormone Replacement Therapy (HRT) in Men and Women

Hormone replacement therapy should be tailored based on sex-specific needs, with transdermal estradiol being the preferred formulation for women and testosterone gel for men with documented hypogonadism, while carefully considering individual risk factors for adverse events. 1

HRT in Women

Indications

• Vasomotor symptoms (hot flashes, night sweats)
• Genitourinary symptoms (vaginal dryness, dyspareunia)
• Prevention of osteoporosis
• Premature ovarian insufficiency (POI)

Formulations and Administration

1. Preferred Estrogen Formulation:

   • Transdermal estradiol (0.025-0.0375 mg/day patch) is preferred over oral formulations due to:
     • More physiological serum estradiol concentrations
     • Better safety profile
     • Minimal impact on hemostatic factors
     • More beneficial effect on lipids, inflammation markers, and blood pressure 1

2. For Women with Intact Uterus:

   • Must add progesterone to prevent endometrial cancer
   • Preferred progesterone: Micronized progesterone 200 mg orally daily 1
   • Alternative: Medroxyprogesterone acetate 2.5 mg/day 1

3. For Women Post-Hysterectomy:

   • Estrogen-only therapy (no progesterone needed) 1

Monitoring and Follow-up

• Initial follow-up at 3 months
• Annual follow-up thereafter
• Monitor: blood pressure, weight, lipid profile, symptom control, and bleeding patterns 1
• No routine monitoring tests required unless prompted by specific symptoms

Duration of Therapy

• For menopausal symptoms: Use lowest effective dose for shortest possible time 2
• For POI: Continue at least until average age of natural menopause (around 51 years) 1
• Discontinuation: Gradual reduction by 25-50% every 4-8 weeks 1

Risks and Contraindications

• Absolute Contraindications:

  • History of hormone-related cancers
  • Active liver disease
  • Abnormal vaginal bleeding
  • Previous venous thromboembolism or stroke
  • Coronary heart disease 1

• Risks of Combined Estrogen-Progestin Therapy (per 10,000 women/year):

  • 7 additional CHD events
  • 8 more strokes
  • 8 more pulmonary emboli
  • 8 more invasive breast cancers
  • But 6 fewer cases of colorectal cancer and 5 fewer hip fractures 2

Alternative Treatments for Women

When HRT is contraindicated:

• SSRIs/SNRIs (venlafaxine, paroxetine, desvenlafaxine)
• Gabapentin
• Clonidine
• Cognitive behavioral therapy and hypnosis
• Vaginal moisturizers and lubricants for local symptoms 1

HRT in Men

Indications

Testosterone replacement is indicated for:

• Primary hypogonadism: testicular failure due to conditions like cryptorchidism, bilateral torsion, orchitis, Klinefelter's syndrome, chemotherapy, or toxic damage
• Hypogonadotropic hypogonadism: gonadotropin or LHRH deficiency or pituitary-hypothalamic injury 3

Important Limitations

• Not indicated for "age-related hypogonadism" or "late-onset hypogonadism"
• Not established for males under 18 years 3

Diagnosis Confirmation

• Serum testosterone must be measured in the morning on at least two separate days
• Confirm levels are below the normal range before initiating therapy 3

Formulations and Dosing

• Recommended Starting Dose: 40.5 mg testosterone gel 1.62% applied topically once daily in the morning to shoulders and upper arms
• Dose Range: 20.25 mg to 81 mg testosterone
• Titration: Based on pre-dose morning serum testosterone at 14 and 28 days after starting treatment 3

Monitoring

• Assess pre-dose morning total serum testosterone concentration
• Adjust dose according to levels:

  • 750 ng/dL: Decrease daily dose by 20.25 mg

  • 350-750 ng/dL: No change
  • <350 ng/dL: Increase daily dose by 20.25 mg 3

Risks and Precautions

• Secondary exposure risk to women and children
• Monitor patients with benign prostatic hyperplasia (BPH)
• Risk of venous thromboembolism
• Potential increased risk of myocardial infarction and stroke
• May lead to azoospermia
• Edema with or without congestive heart failure in patients with preexisting cardiac, renal, or hepatic disease
• Sleep apnea in those with risk factors 3

Special Considerations

Young Women with Premature Ovarian Insufficiency

• For cancer survivors and transplanted patients with POI:
  • Transdermal 17β-Estradiol-based HRT is first choice for safety profile
  • Combined oral contraceptives only if contraception is a priority 2
• Strict follow-up is essential, including:
  • Breast self-examination
  • Annual imaging from age 25 years onwards
  • Consider breast MRI for high-risk young women 2

Complementary Measures

• Regular weight-bearing exercise
• Maintaining healthy weight
• Smoking cessation
• Adequate calcium and vitamin D intake 1

Clinical Decision Algorithm

1. Confirm diagnosis:

   • Women: Menopausal symptoms or premature ovarian insufficiency
   • Men: Morning testosterone levels below normal range on two separate days

2. Assess contraindications:

   • History of hormone-sensitive cancers
   • Cardiovascular disease
   • Thromboembolic events
   • Liver disease

3. Select appropriate formulation:

   • Women with intact uterus: Transdermal estradiol + progesterone
   • Women post-hysterectomy: Estrogen-only therapy
   • Men: Testosterone gel applied to shoulders and upper arms

4. Monitor appropriately:

   • Women: 3-month initial follow-up, then annually
   • Men: Check testosterone levels at 14 and 28 days, then periodically

5. Adjust therapy based on response and safety:

   • Titrate dose based on symptoms and hormone levels
   • Consider discontinuation or alternatives if adverse effects occur