Menopause

Question 1

Background

Answer 1

Menopause = when menstruation stops permanently due to the loss of ovarian follicular activity. (NO longer have children)
Average age is 51
Early menopause = 40-45

Perimenopause = the period before the menopause characterized by irregular cycles of ovulation and menstruation and ends 12 months after last menstrual period.
Last 2 - 8 years. Is a decline of oestrogen bc depletion of ovarian follicles. So, progesterone declines too.
So NO negative feedback = elevated FSH and LH.
Due to less oestrogen can get VMS symptoms. Increases body temp, promote heat loss by vasodilation and sweating. Then the menstrual cycles become anovulatory (without ovulation(eggs)).
Estradiol production decreases too so can’t stimulate endometrium and amenorrhoea begins.
Eventually pattern of low oestrogen and high FSH and LH established.

Post menopause = no period for 1 year.

Premature ovarian insufficiency (POI) = transient or permanent loss of ovarian function before 40 years.

Question 2

Signs and Symptoms

Answer 2

Symptoms will start in perimenopause and carry on post menopause. Every person will have different experience.

Decreased muscle mass, Bone loss

• Mental symptoms:
  Anxiety, mood swings, brain fog (concentration/memory issues)
• VMS vasomotor symptoms:
  hot flushes, Night sweats, Sleep disturbance, daytime fatigue
• Irregular periods (shorter cycles <25 days possible) - eventually will stop having any periods
• Urogenital mucosa:
  Vaginal dryness, irritation, infection chance increase, painful sex, reduced libido, dysuria
• CV:
  Increase in BP, increase in cholesterol (BC estradiol decrease) = More risk of MI

Question 3

Diagnosis/Assessment

Answer 3

Diagnosis of periM or M should be sus if:
- Is a change to the menstrual pattern.
- Are symptoms inc. VMS, mood disorders, urogenital S, altered sexual function, sleep disturbance, and fatigue.
Diagnose if:
- PeriM = VMS + Irregular periods
- M = NO periods for 1 year (MIN)
- M = if women has no uterus = use symptoms

DONT USE Blood test for FSH levels in healthy women not on hormonal contraception >45 yrs.

USE BLOOD TEST for FSH IN:
- >45 years + atypical symptoms;
- Aged 40–45 years + symptoms; and
- <40 years + SUS POI.
- >50 Using DPMA (depot medroxyprogesterone) (if FSH in premenopausal range carry on for 1 year then review)

Assessment
ASK on:
- Symptoms
- Potential causes of amenorrhea
- Life style factors
- Co morbidities
- Family Hx of premature M or POI
- Treatment goals
EXAMINE BP, BMI.
IF sudden change in menstrual pattern urgent 2 week referral if gynaecological cancer sus

Question 4

Complications of P/M

Answer 4

Postmenapause ppl Increased risk of:
- Osteoporosis
- CVD
- Stroke

Early menopause ppl increased risk of:
- CVD
- T2DM
- Osteoporosis
- Depression

Question 5

Treatment - HRT Choice (BNF)

Answer 5

Oestrogen & Progesterone’s:
Women with uterus
- Give cyclical progesterone’s for last 12/14 days of cycle OR preparation which gives continuous administration of oestrogen & progesterone

Oestrogen alone:
For continuous use in women without a uterus except in endometriosis + Progesterone.

• Progesterone ADDED to women with a uterus on long term therapy to reduce cancer/cystic hyperplasia. can be cyclically or continuously

Question 6

Treatment/Management (CKS)

Answer 6

Mainly to manage symptoms:
But give lifestyle advise and info on Menopause etc.

Mild symptoms = OTC, Vaginal lubricants.

SHORT TERM SYMPTOMS:
- VMS = HRT- (Combined can be oral or transdermal). Oestrogen only if no uterus

• Psychological S = Consider HRT (ORAL or TRANSDERMAL) + CBT
• Altered sexual function = consider HRT
  ALT Testosterone supplements for low libido
• Urogenital S = 1st line Low dose Vaginal oestrogen cream PRN
  ALT trial of oral ospemifene
  FOR HRT ALT can be tibolone reduces oestrogen deficiency and osteoporosis fragility fracture risk.

NON HORMONAL TREATMENTS:
Advise on lifestyle measures
VMS = Options:
- Trial SSRi or SNRi 2 weeks
Options = fluoxetine (20mg daily), citalopram (20mg daily), paroxetine (10mg daily), or venlafaxine MR (37.5mg daily for 1 week then 75mg OD if needed).
- Clonidine - Initially 50 mcg BD for 2 weeks, then 75mcg BD, if needed
- Gabapentin - Up to 300mg TDS, initial dose should be lower and titrated up over 3 days.
- CBT
Mood disorder= CBT trial, antidepressant if confirmed depression
- Urogenital S= Vaginal moisturizers (Replens MD®2/7)/lubricants

LONG TERM SYMTPOMS:
Refer complications/benefit of HRT

Question 7

OSTEPOROSIS

Answer 7

1ST LINE bisphosphonates - Alendronic acid or Risedronate sodium ALT oral Ibandronic acid
ALT parenteral Bisphosphonates or Denosumab If cant use ORAL.
EXTRA ALT raloxifene or strontium.
HRT another extra ALT BUT restricted to younger post Menopausal. HRT then tibolone

SEVERE osteoporosis Teriparatide. Romosozumab - severe osteoporosis who have previously EXP fragility fracture and at risk of another (within 2 yrs)
When 1 severe or 2 moderate vertebral fractures teriparatide or romosozumab > Oral bisphosphonates

MOA:
Bisphosphonate - Inhibit osteoclasts activity and promote apoptosis.
Raloxifene - increasing osetoblast acitivty and reduce osetoclast activity
Strontium - stimulates bone formation and reduces bone resorption
Teriparatide - stimulate osteoblast numbers and decrease osteoblast apoptosis
Romosozumab - humanised monoclonal antibody that inhibits sclerostin, = increase bone formation and decrease bone resorption.

Question 8

Complications/Benefits of HRT

Answer 8

COMPLICATIONS:
- VTE - Increased with combined/oestrogen HRT esp in 1st yr. > risk oral vs patch. Patch 1st IF VTE risk and BMI>30.
- Stroke - Risk increases with age. HRT slight increase risk. Tibolone higher increase.
- CVD - No affect IF started on <60 yrs
- Increases risk of CHD in women who start 10 yrs after menopause

OBE cancers
- Ovarian cancer increased risk with long use but disappears within few years of stopping.
- Breast cancer - ALL HRT (inc tibolone) increases risk within 1 yr of use. Combined> increase than others. Longer use further increases risk. Risk disappears within 5 yrs of stopping.
- Endometrial cancer - depends on dose & duration of oestrogen only HRT. Progesterone’s cyclically reduce risk (in women with uterus). Risk is eliminated if progesterone given continuously but increases breast cancer risk.

BENEFITS:
- Osteoporosis - Risk of fragility fracture decreased with HRT.
- VMS symptoms reduced
- Atrophy of urogenital organs reduced

Question 9

PRSC notes

Answer 9

HRT
Uses minimum effective dose for shortest duration - Review at least annually and consider ALT treatments for osteoporosis
- Benefits of short term treatments outweighs long term risk esp in <60s

Oestrogen:
For HRT can get natural or synthetic.
- Natural better for HRT
Oestrogen can be given cyclically or continuously. Oestrogen can cause VTE.
- Progesterone ADDED to women with a uterus on long term therapy to reduce cancer/cystic hyperplasia.
- Progesterone’s dont cause VTE. They only work with women who has a uterus.

Tibolone - Combines oestrogenic/ Progestogenic activity with androgenic activity given WITHOUT Cyclical progesterone. - not needed as already has progesterone activity

Clonidine - Used to reduce menopausal symptoms if unable to use oestrogen.
- Can cause BAD AEs

Ethinylestradiol (HRT a oestrogen)
- Short term symptoms of oestrogen deficiency
- Osteoporosis prophylaxis
- Female hypogonadism & menstrual issues

Raloxifene:
- Treatment & prevention of postmenopausal osteoporosis
unlike HRT dont reduce VMS

Question 10

Starting and stopping HRT/ Surgery

Answer 10

Vaginal bleeding can occur for 1st 3 months WHEN USING HRT should report at 3 month appointment. Can gradually reduce or rapid stop HRT.
- Gradual reduce = decrease short term symptom. Long term no difference.

Symptoms that mean STOP HRT (EXAM Q)
- Sudden sever chest pain/Breathlessness,
- Unexplained swelling or severe pain in one leg,
- Sever stomach pain,
- serious neurological effects (visual issues, headaches, seizure, 1 side numb, fainting),
- Hepatitis, Jaundice, Liver enlargement
- Prolonged immobility after surgery or leg injury

Women with, or at high risk of, breast cancer:
- Give info on treatment available
- Inform that SSRi’s paroxetine and fluoxetine AVOID WITH TAMOXIFEN

Surgery
Major surgery is a predisposing factor of VTE
- STOP HRT 4/6 weeks b4 surgery and restart after full PT mobilisation
IF CANT STOP - prophylaxis with LMWH

Question 11

Review/Referral (EXTRA)

Answer 11

SHORT TERM/non Hormonal:
Review at 3 months then annually. Refer if symptoms don’t improve.
- Any AEs - change/reduce dose, change form. Switch to a combined oestrogen/ bazedoxifene acetate preparation if Progesterone only fails.

Referral to a specialist offered if:
- Ongoing symptoms despite treatment.
- Persistent, troublesome AEs.
- Uncertainty about the most suitable treatment option.
- Uncertainty about the diagnosis or management of POI.