W13 Hormone Replacement Therapy (JD)

Question 1

What is the mean natural age of menopause?
What indicates that a woman is experiencing menopause?

Answer 1

51 years.
Menopause is when menstruation stops permanently due to the loss of ovarian follicular activity. It occurs with the final menstrual period and is usually diagnosed clinically after 12 months of amenorrhoea (no period).

Question 2

4 Stages?

Answer 2

Premenopause - no vasomotor symptoms
Perimenopause - decline in oestrogen level
Menopause
Postmenopause

Question 3

What is perimenopause?

Answer 3

• Perimenopause is the period before the menopause characterized by irregular cycles of ovulation and menstruation and ends 12 months after the
  last menstrual period.

Question 4

What is postmenopause?

Answer 4

Postmenopause is the time after a woman has not had a menstrual period for 12 consecutive months.

Question 5

Menopause symptoms

Answer 5

Vasomotor symptoms
* Hot flushes, night sweat (70 – 80%)
* Cognitive impairment and mood changes
* Anxiety, mood swings, irritability, sleep disturbance, and reduced quality of life
Urogenital symptoms
* Burning, itching, and/or dryness, urinary
frequency, UTIs
Other symptoms
* Joints and muscle pain, headache, fatigue

Question 6

Which of the following is/are routinely considered to diagnose perimenopause?
A. Symptoms (including hot flashes and night sweat)
B. A change to the menstrual pattern
C. Serum follicle-stimulating hormone (FSH)
D. Pelvic Examination

Answer 6

A,B
C- not helpful as it can fluctuate monthly

Question 7

Indications of HRT? (4)

Answer 7

• Menopausal symptoms
• Endometriosis
• Premature ovarian insufficiency
• Heavy menstrual bleeding

Question 8

Indication of HRT in perimenopause and menopause

Answer 8

• Relief of short-term vasomotor symptoms e.g., hot flushes
• Alleviate low mood as a result of the menopause
• Urogenital atrophy (vaginal preparation)
• Prevention of osteoporosis in postmenopausal women- at high risk of future fractures (not 1st line)

Question 9

How effective is HRT?
What is the Main component of HRT?

Answer 9

• Most effective intervention for managing menopausal symptoms.
• Oestrogen- effective in controlling menopausal symptoms
  -Available in different dosage forms
  -Patients’ preference, risk factors, etc. determine which is the most suitable
  dosage form to be used
• Progestogens are available in the form of:
  -natural micronised progesterone tablets
  -synthetic progestogens – oral tablets, patches, intrauterine progestogen releasing system.

Question 10

HRT:
Testosterone replacement therapy in female:
what is it used for?

Answer 10

• improve symptoms of low libido and low sexual drive and improve mood and low
  energy levels
• There are NO testosterone preparations available that are licensed for female use in
  the UK
• Gel – common practice to use gel preparation in female replacement doses (licensed for use in men)
• Implants (off license, limited availability)
  (can be added to other HRT if not effective as monotherapy)

Question 11

Factors that determine the type of HRT? (Oestrogen-only versus combined HRT): (5)

Answer 11

• Whether patient has an intact uterus or not (e.g., subtotal or radical hysterectomy)
• Whether patient is still having periods
• Past medical and family history (e.g., cardiovascular risk factors)
• Past medications history
• Individual preferences

Question 12

HRT is associated with what risk?

Answer 12

=Increased risk of clot formation
oral oestrogen may alter clotting factor in the liver (goes through first pass effect)
transdermal oestrogen reduces this effect (gel,patch,spray)

Question 13

What is the best formulation of systemic HRT to choose, oral or transdermal (patch/gel)?

Answer 13

Multiple factors can be considered when determining which route of administration is best for the patient.
* Patient co-morbidities/risk factors
* Transdermal route preferred in the following circumstances:
* Oral HRT associated with adverse effects (e.g., nausea)
* Increased risk of VTE (e.g., smokers, overweight)
* Cardiovascular risk factors (e.g., hypertension, hypertriglyceridemia, diabetes)
* Impaired liver function

• Patient preference
• Prescriber preference

Question 14

HRT:
Risks (2)
Benefits (3)

Answer 14

• Reduction of vasomotor symptoms.
• Maintenance of bone mineral density and reduced risk of osteoporotic fractures.
• Depend on age and duration of use and dose
• Increased risk of breast and endometrial cancer
  -The risk of endometrial cancer is reduced (back to baseline) by the addition of a progesterone
• Increased risk of clotting (VTE, PE, stroke)

Question 15

Risk of serious complications due to HRT: how to prevent this?

Answer 15

• Overall, the risk of serious complications due to HRT increases with increasing age, dose and duration of treatment.
• Patients should be prescribed the lowest effective dose for the shortest duration possible
• Patients should be regularly reviewed by their doctor (at least yearly) and reassessed as to whether treatment needs to be continued.

Question 16

Contraindication
DO NOT prescribe HRT in women:

Answer 16

• Current, past, or suspected breast cancer.
• Known or suspected oestrogen-dependent cancer.
• Undiagnosed vaginal bleeding.
• Untreated endometrial hyperplasia.
• Previous idiopathic or current VTE (deep vein thrombosis or pulmonary embolism),
  unless the woman is already on anticoagulant treatment.
• Active or recent arterial thromboembolic disease (for example angina or myocardial
  infarction).
• Active liver disease with abnormal liver function tests.
• Pregnancy.
• Thrombophilic disorder.

Question 17

Prescribe HRT WITH CAUTION in women with:

Answer 17

• Porphyria cutanea tarda (photosensitivity).
• Diabetes mellitus (increased risk of heart disease).
• Factors predisposing to venous thromboembolism (recent major surgery, major
  injury, recent infectious disease).
• History of endometrial hyperplasia.
• Migraine and migraine-like headaches.
• Increased risk of breast cancer (older age, low socioeconomic background).

Question 18

Counselling points of HRT

Answer 18

• Explain the risks and benefits of HRT
• Explain to patients about bleed patterns
• Emphasise the importance of treatment adherence
• Advise patients that symptoms will usually start to improve by 4 weeks after HRT initiation.
• Weight gain is very common around the time of the menopause – HRT does not cause significant further weight gain.
• Counsel patients on continuing need to engage in national screening programmes including breast and cervical screening programmes.
• Menopause women are at increased risk of osteoporosis – encourage
  healthy diet (rich in calcium), vitamin D supplementation, weight-bearing
  and resistance exercise.
• Isoflavones (soy), black cohosh and red clover may help relive vasomotor
  symptoms – safety is unknown
• Patients with vaginal dryness
  -OTC vaginal moisturisers and vaginal lubricants
• Lifestyle modifications should be implemented at the same time as medical management – they should not delay treatment initiation

Question 19

Tibolone Livial®

Answer 19

• Tibolone is used as an alternative to combined
  continuous HRT in postmenopausal women
• Has both agonist and antagonist properties:
• Estrogenic effect on thermoregulatory centres in the brain, vagina and bone. Hence helps with vasomotor symptoms, urogenital symptoms and osteoporosis
• Progestogenic and anti-estrogenic effects on endometrium
  and breast. Therefore, does not require opposition with progesterone, and its use is associated with a reduced incidence of mastalgia (breast pain)
• Androgenic effects which help decrease high density
  lipoproteins and triglycerides and increase libido
• Tibolone has the same indications and contraindications as the systemic oestrogen HRTs
• its use is limited by its side effects (increased risk of
  stroke and breast cancer recurrence)

Question 20

Combined oestrogen/bazedoxifene acetate (Duavive® )

Answer 20

• Bazedoxifene acetate is a third-generation selective oestrogen receptor modulator (SERM)
• Bazedoxifene has oestrogen-receptor agonist effects on bone, and antagonist effects on uterine and breast tissue.
• Duavive® is used for the treatment of menopausal symptoms and
  prevention of osteoporosis in post-menopausal women with a uterus if progestogen containing therapy is inappropriate.
• No sufficient data to support its routine use in the UK.

Question 21

Non hormonal therapy
Indication of non-hormonal therapy? (2)
For vasomotor symptoms what is given? (4)

Answer 21

• Patient’s preference
• HRT is not tolerated or contraindicated
• Selective serotonin reuptake inhibitors (SSRIs, off-label) or serotonin and norepinephrine reuptake inhibitors (SNRIs, off-label)
• Clonidine (an alpha-2 adrenergic receptor agonist)
• Gabapentin (off-label)
• Cognitive Behavioural Therapy (CBT)

Question 22

Do the benefits of using HRT outweigh the risks?

Answer 22

Yes
- for the treatment of menopause, short-term outweighs the risks in majority of women, especially in >60yrs.

Question 23

Does HRT increase the risk of CVD?

Answer 23

CVD is the commonest cause of death in postmenopausal women.
Not in women <60yrs
HRT may be cardioprotective in younger postmenopausal women (<10 years from last menstrual period) but the evidence is not currently strong enough to reccomend for primary prevention of CVD

Question 24

How long can menopausal woman take HRT for?

Answer 24

• For symptoms such as hot flushes, 2-5 years but can be longer in some cases
• no greater than 5 years, it is generally considered that the risks of continuing the treatment outweigh the benefits after that period.

Question 25

Does vaginal oestrogen have the same risk as the systemic oestrogen?

Answer 25

No, A women can keep taking it for as long as she needs to control her vaginal dryness

Question 26

Does HRT provide contraception in perimenopausal women?

Answer 26

=No, HRT does NOT provide contraception
Progestogen-only methods of contraception are safe to use alongside cyclical HRT

Question 27

Allana had a hysterectomy 8 years ago. She recently started having troublesome vasomotor symptoms. Assuming she has no contra-indications to HRT use. Which type of HRT is the most appropriate choice for her?
A. Oestrogen-only vaginal HRT
B. Oestrogen and cyclic progestogen HRT
C. Oestrogen only systemic HRT
D. Oestrogen and continuous progestogen HRT

Answer 27

=C

Question 28

1. Linda, a 49-year-old female patient of yours, informs you she has been to her local doctor to discuss treatment of her vasomotor symptoms (VMS).
   * If Linda tells you she still menstruates intermittently every 1-2 months.
   What stage of “menopause” is she in?
2. Let’s assume Linda does have an intact uterus and is still experiencing menstruation. Which HRT would you recommend?
3. Assume Linda has no other medical conditions, takes no other medicines, and with a BMI of 32 kg/m2. Which HRT would you recommend?
   What if?

Answer 28

=Perimenopause
=Sequential therapy
=Transdermal sequential preparation
= Vaginal topical

General counselling information:
* Determine safety
-How do you ask whether a woman has an intact uterus?
* Discuss the risk of DVT
-Red, swollen- or painful leg, difficulty in breathing or chest pain
* Discuss the risk of ca
* Do regular monthly breast exam
-Monitor for changes in your breast (e.g. skin or nipple changes or a lump)
* Report any changes in vaginal bleeding that start a few months after starting HRT
-Heavy or irregular bleeding/spotting or bleeding after intercourse