Sex steroids in hormone replacement

Question 1

How are sex steroids transported in the circulation

Answer 1

Sex hormone binding globulin Bound to binding proteins Unbound in plasma (active form).

Question 2

Hormonal preparations of sex steroids

Answer 2

Local: Creams, gels, vaginal rings

Systemic preparations: oral, transdermal patches, implants

Can be oestrogen alone, combine oestrogen and progesterone, SERMs, gonaomimetics

Natural preparations are rapidly metabolised by the liver, therefore synthetic hormones tend to be used instead

Question 3

SERMS

Answer 3

Selective Oestrogen Receptor Modulators

Question 4

Describe the symptoms caused by changes in menopause

Answer 4

Changes in menopause caused by a loss of follicle activity, therefore oestrogen is not produced. Falling levels cause symptoms.

1. Hot flushes: due to vasomotor instability. Oestrogen affects neurotransmittion in the hypothalamus which is responsible for thermoregulaton.
2. Irregular cycles and eventual ammenorrhea
3. Urogenital symptoms caused because tissues in the urogenitl tract are very sensitive to oestrogen. Loss causes tissue atrophy, loss of elasticity and moist mucosal surface and change in pH. Vaginal dryness common.
4. Neurological symptoms: hot flushes interfere with sleep patterns, increased forgetfulness, tiredness and fatigue.
5. Osteoporosis: oestrogen inhibits osteoclasts, helps regulate bone metabolism. Common changes are seen in the wrists, forearm and spine. Compression fractures in the vertebral column.
6. Lower HDL:LDL ratio, oestrogen normally promotes higher HDL levels. Increases CV risk.

Question 5

Benefits of HRT

Answer 5

Improves vasomotor symptoms

Improves urogenital symptoms

Reduces fracture risk/osteoporosis

Question 6

Risks of HRT

Answer 6

Breast cancer

CV risk e.g. MI

Stroke

Venous thromboembolism

Gall bladder disease

Endometrial cancer in oestrogen only treatment

Question 7

Recommendations for HRT use

Answer 7

Lowest possible dosage given.

Short duration, risks associated with HRT decrease once you come off it.

Oestrogen given with progesterone if uterus is intact to avoid unwanted proliferative effects

Continued surveillance required

Question 8

Adverse effects of HRT in the menopause

Answer 8

Oestrogen: fluid retention, breast tenderness

Progesterone: acne

Combined: menstrual bleed

Question 9

What should you be aware of when administering tamoxifen?

Answer 9

Tamoxifen is a SERM which is an antagonist for oestrogen receptors in the breast, and is used in breast cancer. However it acts as an agonist in the endometrium. Therfore patietns have an increased risk of endometrial cancer and should be monitored.