Hormone Replacement Therapy (HRT)

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Hormone replacement therapy (HRT) is used to relieve moderate to severe vasomotor symptoms and urogenital symptoms, and to prevent osteoporosis.

It replaces oestrogen and progesterone, which are no longer being produced. Progestogens are included in patients with a uterus to prevent endometrial hypertrophy since unopposed oestrogen therapy causes a 5 – 10 x increased risk of endometrial carcinoma.

HRT should be limited to less than 5 years to reduce the risk of adverse effects, and the dose should be tapered over 2 -3 months when stopping treatment. The risks of HRT are greater in women > 60 years.

Hormone replacement therapy preparations

PreparationDescription
Combined HRTEstrogen + progesterone for patients with an intact uterus. Includes cyclical and non-cyclical (continuous) HRT
Cyclical HRTEstrogen is taken daily and progestogens are taken for part of the month. This is best for perimenopausal patients
Non-cyclical HRTBoth oestrogen and progesterone are taken daily without interruption. Best in post-menopasual women
Oestrogen only HRTThis is only for patients who have had a hysterectomy
  • Principles of hormone replacement therapy
    • Combined oral contraceptive pill or intrauterine device if perimenopausal
    • Combined oestrogen and progesterone therapy for all patients with a uterus
    • Oestrogen only therapy for patients without a uterus
    • Start with a small dose and titrate upwards
    • Mammography 3 months after starting treatment
    • Review at 6 month intervals
    • Aim to stop treatment at 2 years
      • If the patient is still unable to tolerate menopause symptoms continue for up to 5 years
  • Hormone replacement therapy options
    • Topical vaginal preparations
      • Given for 6 – 8 weeks for urogenital symptoms
    • Trandermal oestrogen patches
      • Applied weekly
    • Transdermal topical gel
    • Implants
      • Given every 3 – 12 months
    • Cyclical or Continuous oral preparations
    • Synthetic steroids, e.g., tibolone
      • These hasve oestrogen, progestin and testosterone effects
    • Testosterone implant
      • To improve libido
  • Non-hormonal options for post-menopausal symptoms
    • SSRIs are second-line for vasomotor symptoms
    • Gabapentin
    • Clonidine
  • Caution
    • Added progestins to topical vaginal preparations can increase the risk of endometrial cancer
    • Unopposed oestrogen therapy carries a 5 – 10 times increased risk of endometrial cancer
  • Benefits of oestrogen-containing oral HRT preparations
  • Disadvantages of oestrogen-containing oral HRT
    • Increases the risk of breast cancer
    • Increases the risk of coronary artery disease
    • Increases the risk of stroke
    • Increases the risk of pulmonary embolism
  • Contraindications to HRT
  • Administration of estrogen replacement therapy
    • Intravaginal cream (vagifem)
    • Orally
    • Transdermal
  • Other benefits of estrogen replacement therapy
  • Adverse effects of estrogen replacement therapy
Reference Intervals
Biochemistry
ACTHP: <80 ng/L
ALTP: 5–35 U/L
AlbuminP: 35–50 g/L
AldosteroneP: 100–500 pmol/L
Alk. phosphataseP: 30–130 U/L
α-AmylaseP: 0–180 IU/dL
α-FetoproteinS: <10 kU/L
Angiotensin IIP: 5–35 pmol/L
ADHP: 0.9–4.6 pmol/L
ASTP: 5–35 U/L
BicarbonateP: 24–30 mmol/L
BilirubinP: 3–17 μmol/L
BNPP: <50 ng/L
CRPP: <10 mg/L
CalcitoninP: <0.1 mcg/L
Calcium (ionized)P: 1.0–1.25 mmol/L
Calcium (total)P: 2.12–2.60 mmol/L
ChlorideP: 95–105 mmol/L
CholesterolP: <5.0 mmol/L
VLDLP: 0.128–0.645 mmol/L
LDLP: <2.0 mmol/L
HDLP: 0.9–1.93 mmol/L
Cortisol AMP: 450–700 nmol/L
Cortisol MidnightP: 80–280 nmol/L
CK ♂P: 25–195 U/L
CK ♀P: 25–170 U/L
CreatinineP: 70–100 μmol/L
FerritinP: 12–200 mcg/L
FolateS: 2.1 mcg/L
FSHP: 2–8 U/L ♂; >25 menopause
GGT ♂P: 11–51 U/L
GGT ♀P: 7–33 U/L
Glucose (fasting)P: 3.5–5.5 mmol/L
Growth hormoneP: <20 mu/L
HbA1C (DCCT)B: 4–6%
HbA1C (IFCC)B: 20–42 mmol/mol
Iron ♂S: 14–31 μmol/L
Iron ♀S: 11–30 μmol/L
Lactate (venous)P: 0.6–2.4 mmol/L
Lactate (arterial)P: 0.6–1.8 mmol/L
LDHP: 70–250 U/L
LHP: 3–16 U/L
MagnesiumP: 0.75–1.05 mmol/L
OsmolalityP: 278–305 mosmol/kg
PTHP: 0.8–8.5 pmol/L
PotassiumP: 3.5–5.3 mmol/L
Prolactin ♂P: <450 U/L
Prolactin ♀P: <600 U/L
PSAP: 0–4 mcg/mL
Protein (total)P: 60–80 g/L
Red cell folateB: 0.36–1.44 μmol/L
Renin (erect)P: 2.8–4.5 pmol/mL/h
Renin (recumbent)P: 1.1–2.7 pmol/mL/h
SodiumP: 135–145 mmol/L
TBGP: 7–17 mg/L
TSHP: 0.5–4.2 mU/L
T4P: 70–140 nmol/L
Free T4P: 9–22 pmol/L
TIBCS: 54–75 μmol/L
TriglyceridesP: 0.50–2.3 mmol/L
T3P: 1.2–3.0 nmol/L
Troponin TP: <0.1 mcg/L
Urate ♂P: 210–480 μmol/L
Urate ♀P: 150–390 μmol/L
UreaP: 2.5–6.7 mmol/L
Vitamin B12S: 0.13–0.68 nmol/L
Vitamin DS: 50 nmol/L
Arterial Blood Gases
pH7.35–7.45
PaCO₂4.7–6.0 kPa
PaO₂>10.6 kPa
Base excess±2 mmol/L
Urine
Cortisol (free)<280 nmol/24h
Hydroxyindole acetic acid16–73 μmol/24h
Hydroxymethylmandelic acid16–48 μmol/24h
Metanephrines0.03–0.69 μmol/mmol cr.
Osmolality350–1000 mosmol/kg
17-Oxogenic steroids ♂28–30 μmol/24h
17-Oxogenic steroids ♀21–66 μmol/24h
17-Oxosteroids ♂17–76 μmol/24h
17-Oxosteroids ♀14–59 μmol/24h
Phosphate (inorganic)15–50 mmol/24h
Potassium14–120 mmol/24h
Protein<150 mg/24h
Protein/creatinine ratio<3 mg/mmol
Sodium100–250 mmol/24h
Haematology
WCC4.0–11.0 ×10⁹/L
RBC ♂4.5–6.5 ×10¹²/L
RBC ♀3.9–5.6 ×10¹²/L
Hb ♂130–180 g/L
Hb ♀115–160 g/L
PCV ♂0.4–0.54 L/L
PCV ♀0.37–0.47 L/L
MCV76–96 fL
MCH27–32 pg
MCHC300–360 g/L
RDW11.6–14.6%
Neutrophils2.0–7.5 ×10⁹/L (40–75%)
Lymphocytes1.0–4.5 ×10⁹/L (20–45%)
Eosinophils0.04–0.44 ×10⁹/L (1–6%)
Basophils0–0.10 ×10⁹/L (0–1%)
Monocytes0.2–0.8 ×10⁹/L (2–10%)
Platelets150–400 ×10⁹/L
Reticulocytes0.8–2.0% / 25–100 ×10⁹/L
Prothrombin time10–14 s
APTT35–45 s
Paediatric
Pulse Rate (bpm)
Neonate140–160
Infant <1yr120–140
1–5 years110–130
5–12 years80–120
>12 years70–100
Respiratory Rate (tachypnoea)
0–2 months≥60/min
2–12 months≥50/min
1–5 years≥40/min
>5 years≥30/min
Blood Pressure (mmHg)
Term65/45
1 year75/50
4 years85/60
8 years95/65
10 years100/70
Weight Formulas
3–12 months(a + 9)/2 kg
1–6 years2a + 8 kg
>6 years(7a − 5)/2 kg
Haemoglobin (g/dL)
Term newborn13–20
1 month11–18
2 months10–15
1–2 years10–13
>2 years11–14
MUAC (6 months–5 years)
Obese>17.5 cm
Normal13.5–17.4 cm
At risk12.5–13.4 cm
Moderate malnutrition11.5–12.4 cm
Severe malnutrition<11.5 cm
Developmental Milestones
Social smile1.5 months
Head control4 months
Sits unsupported7 months
Crawls10 months
Stands unsupported10–12 months
Walks12–13 months
Talks18 months
CSF WBC (/mm³)
Term newborn0–25
>2 weeks0–5
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