Menopause & HRT

Question 1

What the stages of menopause?

Answer 1

1. Pre-menopause
2. Premature menopause/Primary Ovary Failure (POF)
3. Perimenopause
4. Menopause
5. Post-menopause

Question 2

What endocrine changes occur at menopause?

Answer 2

Upper centres keep working but there is declining oocyte numbers and the ovary cannot respond causing follicles to diminish which means the ovarian hormone inhibin declines so:

• FSH/LH rise as a result of decreased inhibin and -ve feedback
• Oestrogen is low

Question 3

What is menopause?

Answer 3

A natural life event that occurs typically at 45-60 year old (~51 years old) when women stops their menses and there is a decline in ovarian oestrogen production in which the process i.e. perimenopause lasts for +/- 5 years

Question 4

Why does menopause occur?

Answer 4

1.2 million follicles at birth declines to 1000 by menopause mostly as a result of atresia (degeneration of ovarian follicles which do not ovulate during menstrual cycle) which increases from ~ age 35 NOT ovulation

Question 5

When does fertility decline?

Answer 5

Waves from ~37 years

Question 6

What are the risks when fertility declines?

Answer 6

Miscarriage
Meiotic non-disjunction
Down’s syndrome/Trisomy 21 (longer time-frame to gain mutations)

Question 7

What is meiotic non-disjunction?

Answer 7

1. Failure of a pair of homologous chromosomes to separate in meiosis I
2. Failure of sister chromatids to separate during meiosis II
3. Failure of sister chromatids to separate during mitosis

Nondisjunction results in daughter cells with abnormal chromosome numbers (aneuploidy)

Question 8

Why does symptoms occur in menopause?

Answer 8

Due to FALLING levels of oestrogen rather than low levels

Question 9

What is the main symptom of menopause?

Answer 9

Wide variation and can be relatively asymptomatic but include:
- Oligomenorrhea (perimenopause) > amenorrhea (when menopause reached)

Question 10

What is the classic menopause symptom triad?

Answer 10

1. Hot flushes due to vaso-motor instability
2. Sweats spec. at night
3. Vaginal dryness as urogenital tissues are oestrogen sensitive

Affects 80% but bothers 45%

Question 11

What non-specific menopause symptoms can occur?

Answer 11

Headaches
Migraines
Palpitations
Disturbed sleep
Joint and muscle aches 
Infection

Question 12

What urogenital symptoms of menopause can occur?

Answer 12

Vaginal dryness
Cystitis
Urinary frequency
Urinary incontinence 
Vaginal atrophy
Dyspareunia 
Vulvovaginitis

Question 13

What psychological menopause symptoms can occur?

Answer 13

Loss of concentration
Poor memory
Irritability
Loss of libido
Panic attacks

Question 14

In menopause, connective tissue atrophy can occur. What are the symptoms of this?

Answer 14

Skin thinning
Hair loss
Brittle nails
Aches/pains
Osteopenia > osteoporosis

Question 15

What are the features of osteoporosis?

Answer 15

Loss of bone matrix
Loss of height
Deformity
Fractures

Question 16

How is menopause diagnosed?

Answer 16

1. If occurs at normal age, usually clinically by assessing symptoms/signs
2. If a lady is less than 40 years old and menses have been absence for 12 months do blood test for FSH and if above 30mIU/mL POF is confirmed

Question 17

What is premature menopause?

Answer 17

Premature Ovarian Failure (POF) occurring before the age of 40 years (~1% of women) - does not necessarily mean a lack of viable follicles as in menopause, but there is a disconnect between hormones and ovarian function, or an autoimmune problem

Question 18

What are the risks of premature menopause?

Answer 18

Premature death
Neurological diseases
Psychosexual function
Mood disorders
Osteoporosis
IHD
Infertility

Question 19

What menstrual cycle changes can occur as a result of Premature Ovarian Failure (POF)?

Answer 19

Oligomenorrhoea
Polymenorrhoea
Metrorrhagia (bleeding in between periods)

Question 20

What are the causes of Premature Ovarian Failure (POF)?

Answer 20

Idiopathic
Familiar tendency
Autoimmune/thyroiditis
Genetic (Fragile X, Turners syndrome)
Radiation/chemotherapy/Tamoxifen - oestrogen blockers
Infections e.g. viral
Oophrectomy/total hysterectomy (surgical menopause)

Question 21

What is Hormone Replacement Therapy (HRT)?

Answer 21

Administration of hormones esp. oestrogen to relieve menopausal symptoms with preparations containing natural oestrogen at lower doses than oral contraception and can also include progesterone to avoid cystic endometrial hyperplasia

Question 22

What are the routes of administration of Hormone Replacement Therapy (HRT)?

Answer 22

1. Orally via daily tablets
2. Transdermal patches that last 2 weeks
3. Subcutaneous implants with pellets lasting 6 months w/ progesterone orally at specific times
4. Topical oestrogen creams applied to vagina for urogenital symptoms

Question 23

When is progesterone added to Hormone Replacement Therapy (HRT)?

Answer 23

Always UNLESS the patient has had a hysterectomy as in this case, they do not need to worry about uterus symptoms as their uterus and cervix have already been surgically removed

Question 24

What are the benefits of Hormone Replacement Therapy (HRT)?

Answer 24

Improves menopause symptoms esp. vasomotor and urogenital symptoms

Reduces fracture and osteoporosis by improving ER function in bone, mineral density and reducing osteoclast proliferation

Question 25

What are the adverse effects of Hormone Replacement Therapy (HRT)?

Answer 25

Thromboembolism
Stroke
Breakthrough bleeding
Breast tenderness
Increased risk of breast cancer
Increased dementia risk in >65 year olds

Question 26

What other drugs are available to treat menopausal symptoms?

Answer 26

Selective Oestrogen Receptor Modulator (SERM) e.g. Raloxifene/Tamoxifen which are also used to treat osteoporosis via activating +ve oestrogen-like effects via ER function in bone but NOT in breast or uterus so do not carry with them same breast cancer risk