What are the guidelines for bioidentical hormone replacement therapy (BHRT) in women?

Guidelines for Bioidentical Hormone Replacement Therapy (BHRT) in Women

For women seeking hormone replacement therapy, bioidentical hormone therapy should be approached with caution as there is insufficient evidence to support claims that it is safer or more effective than conventional hormone therapy, and FDA has not approved any bioidentical hormone therapy for prevention of chronic conditions in postmenopausal women. 1

Definition and Regulatory Status

• Bioidentical hormones are derivatives of plant extracts chemically modified to be structurally identical to human endogenous hormones 2
• According to the FDA, "bioidentical hormone replacement therapy" is a marketing term rather than a formally defined drug classification 1
• The safety and effectiveness of compounded bioidentical hormones have not been evaluated through the FDA's drug approval process 1

Evidence for Effectiveness and Safety

• There is low to moderate quality evidence that bioidentical hormone therapy in various forms is more effective than placebo for treating moderate to severe menopausal hot flashes 3
• However, there is also low to moderate quality evidence of higher rates of adverse effects such as headache, vaginal bleeding, breast tenderness, and skin reactions with bioidentical hormone therapy 3
• No data are available about the safety of bioidentical hormones regarding long-term outcomes such as heart attack, stroke, and breast cancer 3
• Small observational studies have shown some improvement in menopausal symptoms with compounded bioidentical hormones:
  • One study showed 25% decrease in emotional lability, 25% decrease in irritability, and 22% reduction in anxiety, but only 14% reduction in night sweats and 6% reduction in hot flashes 4
  • Another study reported that 71.8% of women had better relief of menopausal symptoms with bioidentical hormones compared to conventional therapy 5

Recommended Conventional HRT Approach

For women requiring hormone therapy, the following evidence-based guidelines should be followed:

1. Estrogen Selection:

   • 17-β estradiol is preferred to ethinylestradiol or conjugated equine estrogens for estrogen replacement 1
   • Transdermal estradiol is the preferred method of delivery for women with hypertension 1

2. Progestogen Requirement:

   • Progestogen must be given in combination with estrogen therapy to protect the endometrium in women with an intact uterus 1, 6, 7
   • While there may be advantages to micronized natural progesterone, the strongest evidence of endometrial protection is for oral cyclical combined treatment 1

3. Dosing Principles:

   • Start with the lowest effective dose for the shortest duration consistent with treatment goals and risks 7
   • Typical starting doses:
     • Transdermal estradiol: 0.025-0.0375 mg/day patch 6
     • Oral micronized progesterone: 200 mg daily for 12-14 days per month 6

4. Monitoring:

   • Annual clinical review once established on therapy, with particular attention to compliance 1
   • No routine monitoring tests are required but may be prompted by specific symptoms or concerns 1
   • Reevaluate the need for therapy every 3-6 months 6, 7

Special Populations

1. Women with Premature Ovarian Insufficiency (POI):

   • HRT is indicated for treatment of symptoms and may have a role in primary prevention of cardiovascular disease and for bone protection 1
   • HRT has not been found to increase breast cancer risk before the age of natural menopause 1

2. Women with BRCA1/2 Mutations:

   • HRT is a treatment option after prophylactic bilateral salpingo-oophorectomy if no personal history of breast cancer 1

3. Women with Endometriosis:

   • Combined estrogen/progestogen therapy can be effective for vasomotor symptoms and may reduce risk of disease reactivation after oophorectomy 1

4. Women with Migraine:

   • Migraine should not be seen as a contraindication to HRT use 1
   • Consider changing dose, route of administration, or regimen if migraine worsens during HRT 1

Contraindications for Hormone Therapy

• Active liver disease
• History of breast cancer
• Coronary heart disease
• Previous venous thromboembolism or stroke
• HRT is generally contra-indicated in breast cancer survivors 1, 6

Androgen Therapy

• Androgen treatment is only supported by limited data, and long-term health effects are not clear 1
• If androgen therapy is commenced:
  • Treatment effect should be evaluated after 3-6 months
  • Treatment should possibly be limited to 24 months 1

Important Caveats

• The US Preventive Services Task Force recommends against using hormone therapy for prevention of chronic conditions (Grade D recommendation) 6
• There is no convincing evidence that bioidentical hormones alter the ultimate balance of benefits and harms compared to conventional hormone therapy 1
• Patient preference for route and method of administration should be considered when prescribing, as should contraceptive needs 1
• Gradual reduction of HRT dose by 25-50% every 4-8 weeks is recommended when discontinuing therapy 6

While some women report improved symptom relief with compounded bioidentical hormones, the lack of standardization, quality control, and long-term safety data makes conventional FDA-approved hormone therapy a more evidence-based choice for managing menopausal symptoms.