B16. Hormone replacement therapy guidelines, indications, contraindications, side effects

Definition

Hormone replacement therapy (HRT) or postmenopausal hormonal therapy is used to treat bothersome symptoms of menopause, and to prevent the late consequences of oestrogen deficiency by administering oestrogen with or without progesterone. However, not all patients should receive HRT.

Menopause is a natural state of the body and is not a disorder which requires treatment. However, in those where the symptoms are severe and cause significantly decreased quality of life, it may be used.

Some patients avoid HRT because they don’t want their menstruation to return, and some because they’re afraid of cancer development.

HRT may last for decades, but it should be stopped at the age of 65 – 70. It’s generally only used for 3 – 5 years.

Contraindications

  • Absolute contraindications
    • History of breast or endometrial cancer
    • Active liver disease
    • Active thromboembolic disease
    • Unexplained uterine bleeding disorder
  • Relative contraindications
    • Cured breast cancer
    • Inactive liver disease
    • Endometriosis
    • Uterine fibroids
    • Porphyria

Selecting candidates

In order to select candidates for HRT, we must exclude all contraindications, by performing:

  • History
  • Physical and gynaecological examination
  • Transvaginal ultrasound
  • Breast examination (mammography, ultrasound)
  • Lab tests (FSH, prolactin, LFT, lipids, coagulation
  • Osteodensitometry

There are various risks and benefits which should be measured up against each other before starting HRT:

  • Risks
    • Increased risk for breast cancer
      • Slightly increased risk
      • BUT a lower mortality rate should they be affected
    • Increased risk for endometrial cancer (only in unopposed oestrogen therapy)
    • Thromboembolism (not in case of natural oestrogens)
    • Gallbladder disease
  • Benefits
    • Symptom relief
    • Quality of life
    • Decreased risk for osteoporosis
    • Decreased cardiovascular risk
    • Decreases development of neuro-cognitive disorders
    • Decreased risk for colorectal cancer
    • Decreased risk for cervical cancer
    • Decreased risk of diabetes
    • Decreased mortality
      • HRT users live 3 – 4 years longer compared to nonusers

If the only symptoms are vaginal, local oestrogen therapy can be used to treat it.

If the perimenopausal symptoms cause moderate or severe distress and decreased quality of life to the patient, and they have no contraindications, and they’re aware of the risks, then it may be started.

Types of hormone replacement therapy

There are various types according to the timing and choice of hormones:

  • Continuous therapy – where no menstruation occurs
    • Continuous oestrogen therapy throughout the 28 day cycle
    • Continuous oestrogen and cyclic progesterone therapy
    • Continuous oestrogen and progesterone therapy
  • Cyclic therapy – where menstruation occurs on the off-cycle
    • Cyclic oestrogen therapy (21 days on, 7 days off)
    • Cyclic oestrogen and progesterone therapy

Oestrogen monotherapy increases the risk for endometrial cancer, and so HRT should always by a combination of oestrogen and progestin to prevent this. The only exception is in women who’ve had hysterectomy, in which oestrogen monotherapy can be used.

There are also multiple types of oestrogens and progestins to be used:

  • Oestrogens
    • Natural oestrogens
      • 17-beta oestradiol (best)
      • Conjugated equine oestrogen
    • Synthetic oestrogens
      • Ethinyl oestradiol
      • Dienestrol
  • Progestins
    • Micronized progesterone (best)
    • Medroxyprogesterone acetate (MPA)
    • Norethisterone
    • Levonorgestrel

The drugs can be administered orally or transdermally.

Related drugs

Selective tissue oestrogenic activity regulators (STEARs) are drugs which have oestrogen agonist effects on the bone, brain, and vagina, but no oestrogenic effect on the breast and endometrium. The most commonly used type is tibolone, which has oestrogen, progesterone, and androgen effects. It may be used for HRT.

Selective oestrogen receptor modulators (SERMs) are drugs which have oestrogen agonist effects on some tissues, and antagonist effects on others. This allows them to have an oestrogen agonist effect on the tissues where it is beneficial to have it, and an antagonist in those where it’s disadvantageous. The most commonly used ones are tamoxifen, raloxifene, and bazedoxifene. However, tamoxifen is mostly used to treat breast cancer, and raloxifene is mostly used to treat osteoporosis. Bazedoxifene is sometimes used in HRT in combination with oestrogens.


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