Menopause

Question 1

Define

Answer 1

Menopause diagnosis = absence of menses for >12 months (retrospective diagnosis)

• Average age 50 (±2); if <45, consider investigating (premature ovarian insufficiency = if <40 yo)
• Depletion of oocytes -> reduction in ovarian production of progesterone, oestradiol, and testosterone

Perimenopause: time of life from the onset of ovarian dysfunction until 1 year after the last period and the diagnosis of menopause is made. This time is also known as climacteric.

• Can last for a few months to few years

Post-menopause: All women who have been 1 year since their last period

• Retrospective diagnosis

Question 2

Aetiology

Answer 2

Cessation of ovarian function- stop producing oestrogen and no longer release eggs

• It is irreversible
• Inhibin B is produced by follicles within the ovary, so as the number of follicles decline, the production of inhibin reduces.
• In the perimenopausal years, small declines in inhibin drive an overall increase in the pulsatility of GnRH secretion and overall serum FSH and LH levels.
• This results in an increased drive to the remaining follicles in an attempt to maintain follicle production and oestrogen levels.
• However this increase in FSH levels, desensitizes the receptors so no ovulation

The ovaries produce 30-50% of the body’s circulating androgen hormone levels.

• There is a decline in ovarian testosterone and androgens as women age
• NOTE: androgens come from the ovaries, peripheral adipose tissue and adrenals

Median age ~ 51-52 years

95% of women go through menopause between the ages of 45-55 years

Question 3

Iatrogenic menopause

Answer 3

Medical treatments and menopause after cancer treatment

• Appropriate counselling before definitive irreversible treatment that may compromise fertility is important
• GnRH agonists (e.g. buserelin) can be used to treat endometriosis and other gynaecological problems but constant stimulation of GnRH receptors leads to desensitisation and reduces LH and FSH release
  
  • This can induce a temporary menopause

Surgical Menopause

• May occur in the surgical management of fibroids, endometriosis and other gynaecological conditions
• Bilateral salpingo-oophrectomy (BSO) may be performed prophylactically in women at high risk for inherited malignancies e.g. breast and ovarian cancer with BRCA 1/2 gene mutation screening
• These women should be counselled so that they can choose a correct time for the procedure and counselling on how to manage the sudden hormone deficit
• They will lose the effect of oestrogen and testosterone

Question 4

Symptoms and signs

Answer 4

Signs & symptoms – approx. 75% get symptoms and last for ~7 years:

• Persistent amenorrhea – often initial oligomenorrhoea/irregular or shortened cycles
• Vasomotor symptoms – hot flushes, night sweats, palpitations, headaches
• Urogenital – vaginal dryness, dyspareunia, frequency, dysuria, recurrent UTI
• Psychological – poor concentration, lethargy, mood disturbance, reduced libido (these present first)

Question 5

Investigations

Answer 5

Pregnancy test

FSH, LH = high (unopposed); serum oestradiol = low (no oocytes to produce)

Prolactin, TFTs, TVUSS (endometrial/ovarian cancer -> bleeding = endometrial; no bleeding and mass = ovarian)

Question 6

Management

Answer 6

Do they have a uterus?

• If no – systemic oestrogen (think about contraindications e.g. DVT)
• If yes – combined with progesterone to protect against endometrial carcinoma

Route of HRT:

• Systemic – oral, implant
• Transdermal – hx of DVT/stroke, etc.
• Topical – hx of DVT/stroke, etc.

Normal menstrual cycle:

• Thecal cells (ovaries and eggs) -> androgens (oestrogen) -> endometrial growth
• Corpus luteum -> progesterone -> secretory change

1st Line = Lifestyle change – exercise, alcohol, caffeine, weight loss, stress reduction

• Hot flushes regular exercise, WL, reduce stress
• Sleep disturbance sleep hygiene (regular, good times), no late evening exercise
• Mood sleep hygiene, regular exercise, relaxation techniques
• Cognitive symptoms sleep hygiene, regular exercise

2nd Line = Hormone Replacement Therapy (HRT)

Oestrogens Alone (Elleste Solo) – ONLY IN POST-HYSTERECTCOMY

• OD, oral oestrogen (standard therapy)
• Transdermal oestrogen patch (BMI >30; due to lower VTE risk)
• N.B. you can have an oestrogen-only preparation combined with an LNG-IUS (Mirena)

Oestrogen with Progestogen (Elleste Duet) – progesterone protects endometrium

• Routes = oral, transdermal (less clot risk), vaginal creams/gel (less clot risk), implant
• Cyclical / Sequential pattern / SCT (peri-menopausal):
• Monthly: oestrogen every day of month + progesterone for the last 14 days
  
  • Indication = regular periods and menopause symptoms
• 3-monthly: oestrogen every day for 3 months + progesterone for last 14 days
  
  • Indication = irregular periods and menopause symptoms
  • Common cause of IMB = endometrial polyp
• Continuous pattern / CCT (post-menopausal – no period for ≥1 year):
  
  • Oestrogen and progesterone every day

Benefits: Improved menopause symptoms

• Vasomotor, sleep, and genital tract symptoms (dryness, dyspareunia)
• Prevention of osteoporosis

Risks:

• Breast cancer (1.2x higher; 22 to 27 per 1,000)
• Cancer:
  
  • Oestrogen-only = breast cancer, endometrial cancer
  • Combined = breast cancer, (endometrial negligible)
  • VTE (2-4x higher; 2 per 1,000 taking HRT over 7.5 years)

· Side-Effects – should pass in a few weeks of starting HRT:

• Oestrogenic: breast tenderness, nausea, headaches
• Progestogenic: fluid retention, mood swings, depression
• Unscheduled vaginal bleeding (common in first 3 months of HRT)
  
  • Sequential > continuous HRT
  • Investigate if it continues past 6 months (or after a spell of amenorrhoea)

Vasomotor symptoms:

· 1st line (SSRIs) -> fluoxetine

· 2nd line -> citalopram, venlafaxine

· 3rd line (ongoing research) à gabapentin

· Alpha agonists (clonidine) are licenced but there are lots of anti-ACh side effects…

Vaginal dryness:

· Lubricants

Osteoporosis treatments (e.g. bisphosphonates)

Question 7

Contraindications of HRT

Answer 7

ABSOLUTE

• Suspected pregnancy
• Breast cancer- current, past or suspected
• Known or suspected oestrogen-sensitive cancer (e.g. endometrial cancer)
• Untreated endometrial hyperplasia
• Active liver disease
• Uncontrolled hypertension
• Previous idiopathic or current VTE unless already on anticoagulants
• Active or recent arterial thromboembolic disease (e.g. angina, MI)
• Known thrombophilia (e.g. Factor V Leiden)
• Otosclerosis

RELATIVE

• Un-investigated abnormal bleeding
• Large uterine fibroids
• Past history of benign breast disease
• Unconfirmed personal history or a strong family history of VTE
• Chronic stable liver disease
• Migraine with aura

Question 8

Complications

Answer 8

• Menopause
• Cardiovascular disease
• Urogenital problems- UTIs, atrophy
• Sexual dysfunction
• Osteoporosis

Question 9

Side effects of HRT

Answer 9

SAFETY NET

• Bleeding persistent after 3-6m
• Potentially may need to increase progesterone
• But warn they may experience a bit of bleeding after
• If heavy bleeding after come and see them

HRT in older women (>65 y/o) may increase the risk of cardiovascular disease and stroke

HRT doubles risk of VTE

NOTE: transdermal HRT may not have a great effect on VTE incidence (by avoiding effects on the liver and reducing effects of hepatic clotting system).

Question 10

Prognosis

Answer 10

Hot flushes may resolve after 5-10 years

Urogenital atrophy may stay the same or worsen

Women with untreated premature menopause and early perimenopause (between 40-50 years) are at increased risk of mortality and serious morbidity (due to decreased oestrogen), including:

• CVD
• Cognitive decline
• Dementia
• Parkinsonism
• Osteoporosis

Postmenopausal women are at increased risk of:

• Osteoporosis
• CVD
• Stroke
• Atrophic changes in the vagina and bladder (due to oestrogen depletion and natural ageing)

Question 11

PACES

Answer 11

Explain menopause

• Time when a woman stops getting their period and is no longer able to get pregnant
• Every woman goes through it at some point in their lives
• For some this can inc… (talk about their symp)

Lifestyle

• Reg exercise, reducing stress, relaxation tech
• Improve sleep hygiene (avoid caffeine, late night exercise etc)
• Counselling/ advice
• Symptoms can last for a few years, this varies from woman to woman, however, the treatment options available are very effective for managing these symptoms.

Depending on what you prefer, we can give you hormonal or non-hormonal medication to treat the symptoms you are currently having.

Our recommendation for women is usually Hormone Replacement Therapy.

• Explaining combined
• Estrogen alone can cause abnormal thickening of the lining of your uterus, which can lead to bleeding. Adding progestogen will prevent this. Progestogen may be given in the form of tablets, patches or a hormone­containing coil.
• If combined HRT is started before you have the menopause or within 12 months of your last period then you will be offered a ‘cyclical’ combined HRT, which should give you regular monthly withdrawal bleeds.
• If you start combined HRT more than 12 months after your last period, you may be offered ‘continuous’ combined HRT (bleed­free HRT). You may experience some vaginal bleeding in the first 3 months, but after this it should stop.

Explaining estrogen only

• If you have had a hysterectomy then you will be offered estrogen only HRT.
• Oral or patch (prefer patch if BMI >30 and clots in past)
• Review initially in 2 months and then yearly review - check symptoms, BMI, BP and side effects.

Safety

• The effects of HRT have been studied worldwide and research shows that, for most women, HRT works and is safe.

Benefits

• It is an effective treatment for hot flushes and low mood associated with the menopause.
• It can improve sexual desire and reduce vaginal dryness.
• It helps keep your bones strong by preventing osteoporosis.

Risks

• HRT with estrogen alone (used for women who have no uterus) is associated with little or no increased risk of breast cancer.
• HRT with estrogen and progestogen can increase your risk of breast cancer. This risk is higher the longer you stay on it and reduces when you stop HRT.
• Your individual risk of developing breast cancer depends on underlying risk factors, such as your body weight and your drinking and smoking habits.
• HRT taken as a tablet increases your risk of developing a blood clot, which is not the case if HRT is taken as a patch or gel.
• HRT in tablet form slightly increases your risk of stroke, although the overall risk of stroke is very low if you are under the age of 60 years.

Non-Hormonal (Non-HRT)

• SSRIs e.g. fluoxetine to help with hot flushes/vasomotor symptoms Lubricants to help with vaginal dryness
• Consider CBT if depressed

Contraception

• Needed 1 yr if over 50 and for 2 years if under 50
• POP (contraception) can be used in conjunction with HRT as long as the HRT has a prog component. Whereas, with LNG-IUS, can be used as the prog component so oestrogen only HRT can be used.

If they ask about herbal meds/ alternative therapies

• Plants or plant extracts, such as St John’s wort, black cohosh and isoflavones (soya products), can help reduce hot flushes and night sweats for some women.
• However, their safety is unknown and they can react with other medicines that you may be taking for conditions such as breast cancer, epilepsy, heart disease or asthma.
• If you buy herbal products, look for a product licence or Traditional Herbal Registration (THR) number on the label to ensure that what you are buying has been checked for purity.
• Alternative therapies such as acupressure, acupuncture or homeopathy may help some women. More research is, however, required on the benefits from these therapies
• Commercially available ‘bioidentical’ hormones are not regulated or licensed in the UK owing to lack of evidence that they are effective or safe to use.