Menopause and its abnormalities

Question 1

Define menopause.

Answer 1

Permanent cessation of menstruation resulting from loss of ovarian follicular activity.

Question 2

At what age (average) do women experience menopause?

Answer 2

51 yrs

Question 3

Define postmenopause.

Answer 3

Describes the period from 12 months after the final menstrual period onwards

Question 4

Define perimenopause.

Answer 4

Perimenopause refers to the time around the menopause, where the woman may be experiencing vasomotor symptoms and irregular periods. Perimenopause includes the time leading up to the last menstrual period, and the 12 months afterwards. This is typically in women older than 45 years.

Question 5

Define premature menopause.

Answer 5

Menopause before the age of 40 yrs. It results from premature ovarian insufficiency

Question 6

What are the biochemical results in menopause?

Answer 6

• Low oestrogen and progesterone
• High FSH and LH (in response to absence of oestrogen)

Question 7

Describe the physiology of menopause.

Answer 7

The process of the menopause begins with a decline in the development of the ovarian follicles. Without the growth of follicles, there is reduced production of oestrogen. Oestrogen has a negative feedback effect on the pituitary gland, suppressing the quantity of LH and FSH produced. As the level of oestrogen falls in the perimenopausal period, there is an absence of negative feedback on the pituitary gland, and increasing levels of LH and FSH.

The failing follicular development means ovulation does not occur (anovulation), resulting in irregular menstrual cycles. Without oestrogen, the endometrium does not develop, leading to a lack of menstruation (amenorrhoea). Lower levels of oestrogen also cause the perimenopausal symptoms.

Question 8

What are perimenopausal symptoms?

Answer 8

A lack of oestrogen in the perimenopausal period leads to symptoms of:

• Vasomotor symptoms
  
  • Hot flushes
  • Night sweats
• Urogenital problems
  
  • Vaginal dryness and atrophy
  • Dyspareunia
  • Itching burning dryness
• Sexual problems
  
  • Reduced libido
• Emotional lability or low mood
• Premenstrual syndrome
• Irregular periods
• Joint pains
• Heavier or lighter periods

Question 9

What are the risks of menopause?

Answer 9

• Osteoporosis
• CVD and stroke
• Pelvic organ prolapse
• Urinary incontinence

Question 10

How to we diagnose menopause?

Answer 10

A diagnosis of perimenopause and menopause can be made in women over 45 years with typical symptoms, without performing any investigations.

NICE guidelines (2015) recommend considering an FSH blood test to help with the diagnosis in:

• Women under 40 years with suspected premature menopause
• Women aged 40 – 45 years with menopausal symptoms or a change in the menstrual cycle

Question 11

What advice should we give regarding contraception in the peri and post menopausal period?

Answer 11

Women need to use effective contraception for:

• Two years after the last menstrual period in women under 50
• One year after the last menstrual period in women over 50

Hormonal contraceptives do not affect the menopause, when it occurs or how long it lasts, although they may suppress and mask the symptoms. This can make diagnosing menopause in women on hormonal contraception more difficult.

Question 12

What contraception would you offer women approaching menopause?

Answer 12

Good contraceptive options (UKMEC 1, meaning no restrictions) for women approaching the menopause are:

• Barrier methods
• Mirena or copper coil
• Progesterone only pill
• Progesterone implant
• Progesterone depot injection (under 45 years - due to SEs: reduced bone mineral density)
• Sterilisation

The combined oral contraceptive pill is UKMEC 2 (the advantages generally outweigh the risks) after aged 40, and can be used up to age 50 years if there are no other contraindications. Consider combined oral contraceptive pills containing norethisterone or levonorgestrel in women over 40, due to the relatively lower risk of venous thromboembolism compared with other options.

Question 13

What are the treatment options for perimenopausal symptoms?

• Hot flushes and night sweats
• Vaginal atrophy
• Osteoporosis
• Psychological
• Reduced libido

When are the vasomotor symptoms likely to resolve?

Answer 13

Vasomotor symptoms are likely to resolve after 2 – 5 years without any treatment. Management of symptoms depends on the severity, personal circumstances and response to treatment. Options include:

• No treatment
• Hormone replacement therapy (HRT)

Hot flushes and night sweats

• HRT
• Clonidine act as an agonist of alpha-2 adrenergic receptors and imidazoline receptors
• Isoflavone or black cohosh - helpful but interactions with other medications noted and different preparations exist.

Vaginal atrophy

• Offer vaginal oestrogen to women with urogenital atrophy (including those on systemic HRT) and continue treatment for as long as needed to relieve symptoms.
• If vaginal oestrogen does not relieve symptoms of urogenital atrophy, consider increasing the dose after seeking advice from a healthcare professional with expertise in menopause.
• Counsel:
  
  • Symptoms can come back when tx stopped
  • Adverse effects rare
  • Report any unscheduled bleeding to GP
• Moisturisers such as Sylk, Replens and YES and lubricants can be used alone or in addition to vaginal oestrogen.

Osteoporosis

• Explain to women that the baseline population risk of fragility fracture for women around menopausal age in the UK is low and varies from one woman to another.
• Explain to women that their risk of fragility fracture is decreased while taking HRT and that this benefit:
  
  • is maintained during treatment but decreases once treatment stops
  • may continue for longer in women who take HRT for longer

Psychological

• HRT
• Cognitive behavioural therapy (CBT)
• Only if evidence that they are depressed → SSRI antidepressants, such as fluoxetine or citalopram

Reduced libido:

Consider Testosterone (usually as a gel or cream) supplementation for menopausal women with low sexual desire if HRT alone is not effective

Question 14

When should you review and refer for menopause?

Answer 14

Question 15

Why is combined HRT used in women who have uteri?

Answer 15

Progesterone needs to be given (in addition to oestrogen) to women that have a uterus. The primary purpose of adding progesterone is to prevent endometrial hyperplasia and endometrial cancer secondary to “unopposed” oestrogen

Question 16

What are the indications of HRT?

Answer 16

• Replacing hormones in premature ovarian insufficiency, even without symptoms
• Reducing vasomotor symptoms such as hot flushes and night sweats
• Improving symptoms such as low mood, decreased libido, poor sleep and joint pain
• Reducing risk of osteoporosis in women under 60 years

Question 17

What are the benefits of HRT?

Answer 17

In women under 60 years, the benefits of HRT generally outweigh the risks.

The key benefits to inform women of include:

• Improved vasomotor and other symptoms of menopause (including mood, urogenital and joint symptoms)
• Improved quality of life
• Reduced the risk of osteoporosis and fractures

Question 18

What are the risks of HRT?

Answer 18

Women may be concerned about the risks of HRT. It is crucial to put these into perspective. In women under 60 years, the benefits generally outweigh the risks. Specific treatment regimes significantly reduce the risks associated with HRT.

The risks of HRT are more significant in older women and increase with a longer duration of treatment. The principal risks of HRT are:

• Increased risk of breast cancer (particularly combined HRT – oestrogen-only HRT has a lower risk)
• Increased risk of endometrial cancer
• Increased risk of venous thromboembolism (2 – 3 times the background risk)
• Increased risk of stroke and coronary artery disease with long term use in older women
• The evidence is inconclusive about ovarian cancer, and if there is an increase in risk, it is minimal

These risks do not apply to all women:

• The risks are not increased in women under 50 years compared with other women their age
• There is no risk of endometrial cancer in women without a uterus
• There is no increased risk of coronary artery disease with oestrogen-only HRT (the risk may even be lower with HRT)

Ways to reduce the risks:

• The risk of endometrial cancer is greatly reduced by adding progesterone in women with a uterus
• The risk of VTE is reduced by using patches rather than pills - Consider transdermal rather than oral HRT for menopausal women who are at increased risk of VTE, including those with a BMI over 30 kg/m²

Question 19

What are contraindications of HRT?

Answer 19

• Undiagnosed abnormal bleeding
• Endometrial hyperplasia or cancer
• Breast cancer
• Uncontrolled hypertension
• Venous thromboembolism
• Liver disease
• Active angina or myocardial infarction
• Pregnancy

Question 20

What ix do we need to do before starting a patient on HRT?

Answer 20

Before initiating HRT, there are a few things to check and consider:

• Take a full history to ensure there are no contraindications
• Take a family history to assess the risk of oestrogen dependent cancers (e.g. breast cancer) and VTE
• Check the body mass index (BMI) and blood pressure
• Ensure cervical and breast screening is up to date
• Encourage lifestyle changes that are likely to improve symptoms and reduce risks

Question 21

What three steps do we need to go through when choosing what type of HRT a patient should get?

Answer 21

There are three steps to consider when choosing the HRT formulation:

Step 1: Do they have local or systemic symptoms?

• Local symptoms: use topical treatments such as topical oestrogen cream or tablets
• Systemic symptoms: use systemic treatment – go to step 2

Step 2: Does the woman have a uterus?

• No uterus: use continuous oestrogen-only HRT
• Has uterus: add progesterone (combined HRT) – go to step 3

Step 3: Have they had a period in the past 12 months?

• Perimenopausal: give cyclical combined HRT
• Postmenopausal (more than 12 months since last period): give continuous combined HRT

Question 22

When should we offer oestrogen patches rather than pills?

Answer 22

Patches are more suitable for women with poor control on oral treatment, higher risk of venous thromboembolism, cardiovascular disease and headaches.

Question 23

What is the difference between cyclical and continuous progesterone? Can you switch from one to another?

Answer 23

Cyclical progesterone, given for 10 – 14 days per month, is used for women that have had a period within the past 12 months. Cycling the progesterone allows patients to have a monthly breakthrough bleed during the oestrogen-only part of the cycle, similar to a period.

Continuous progesterone is used when the woman has not had a period in the past:

• 24 months if under 50 years
• 12 months if over 50 years

Using continuous combined HRT before postmenopause can lead to irregular breakthrough bleeding and investigation for other underlying causes of bleeding.

You can switch from cyclical to continuous HRT after at least 12 months of treatment in women over 50, and 24 months in women under 50. Switch from cyclical to continuous HRT during the withdrawal bleed. Continuous HRT has better endometrial protection than cyclical HRT.

Question 24

What are the options for delivering progesterone?

Answer 24

There are three options for delivering progesterone for endometrial protection:

• Oral (tablets)
• Transdermal (patches)
• Intrauterine system (e.g. Mirena coil)

Cyclical combined HRT options include sequential tablets or patches containing continuous oestrogen with progesterone added for specific periods during the cycle.

The Mirena coil is licensed for four years for endometrial protection, after which time it needs replacing. The Mirena coil has the added benefits of contraception and treating heavy menstrual periods. It can cause irregular bleeding and spotting in the first few months after insertion. This usually settles with time and many women become amenorrhoeic.

Question 25

Define

• progestogen
• progesterone
• progestins

Answer 25

The terms around progesterone can be confusing. There are some key definitions to remember:

• Progestogens refer to any chemicals that target and stimulate progesterone receptors
• Progesterone is the hormone produced naturally in the body
• Progestins are synthetic progestogens

Question 26

What type of progestogen is given for HRT? What can we do with them?

Answer 26

There are two significant progestogen classes used in HRT. If the woman experiences side effects, consider switching the progestogen class. They can be described as C19 and C21 progestogens, referring to the chemical structure and number of carbon atoms in the molecule.

C19 progestogens are derived from testosterone, and are more “male” in their effects. Examples are norethisterone, levonorgestrel and desogestrel. These may be helpful for women with reduced libido.

C21 progestogens are derived from progesterone, and are more “female” in their effects. Examples are progesterone, dydrogesterone and medroxyprogesterone. These may be helpful for women with side effects such as depressed mood or acne.

Question 27

What is Tibolone? What is it good for? What are the requirements for its use?

Answer 27

• Tibolone is a synthetic steroid that stimulates oestrogen and progesterone receptors.
• It also weakly stimulates androgen receptors. The effects on androgen receptors mean tibolone can be helpful for patients with reduced libido.
• Tibolone is used as a form of continuous combined HRT. Women need to be more than 12 months without a period (24 months if under 50 years).
• They would be expected not to have breakthrough bleeding. Tibolone can cause irregular bleeding, resulting in further investigations to exclude other causes.

Question 28

What are the considerations we must take when putting a patient on HRT?

Answer 28

• Follow up three months after initiating HRT to review symptom and side effects
• Side effects often settle with time, so it is worth persisting for at least three months with each regime
• It takes 3 – 6 months of treatment to gain the full effects
• Problematic or irregular bleeding is an indication for referral to a specialist
• Ensure the woman has appropriate contraception
• Stop oestrogen-containing contraceptives or HRT 4 weeks before major surgery (NICE guidelines 2018 – NG89)
• Consider other causes of symptoms where they persist despite HRT (e.g. thyroid, liver disease and diabetes)

Question 29

What are the SEs of oestrogen?

Answer 29

Oestrogenic side effects:

• Nausea and bloating
• Breast swelling
• Breast tenderness
• Headaches
• Leg cramps

Question 30

What are the SEs of progestogens?

Answer 30

• Mood swings
• Bloating
• Fluid retention
• Weight gain
• Acne and greasy skin

Question 31

How should HRT be stopped?

Answer 31

Offer women who are stopping HRT a choice of gradually reducing or immediately stopping treatment.

Question 32

What are the causes of post-menopausal bleeding?

Answer 32

 Endometrial Ca
 Endometrial hyperplasia + atypia and polyps
 Cervical carcinoma
 Atrophic vaginitis
 Cervicitis
 Ovarian carcinoma
 Cervical polyps

Question 33

What are the investigations for PMB?

Answer 33

 Bimanual + speculum
 Cervical smear
 TVUS
o Endometrial thickness
o 4mm or less = normal

o Single episode and normal thickness: do not need biopsy
o Multiple bleeds or thickened endometrium: endometrial biopsy + hysteroscopy

Question 34

Define atrophic vaginitis

Answer 34

Atrophic vaginitis refers to dryness and atrophy of the vaginal mucosa related to a lack of oestrogen. Atrophic vaginitis can also be referred to as genitourinary syndrome of menopause. It occurs in women entering the menopause.

Question 35

What happens during atrophic vaginitis? What are other consequences of lack of oestrogen?

Answer 35

• The epithelial lining of the vagina and urinary tract responds to oestrogen by becoming thicker, more elastic and producing secretions.
• As women enter the menopause, oestrogen levels fall, resulting in the mucosa becoming thinner, less elastic and more dry.
• The tissue is more prone to inflammation. There are also changes in the vaginal pH and microbial flora that can contribute to localised infections.
• Oestrogen also helps maintain healthy connective tissue around the pelvic organs, and a lack of oestrogen can contribute to pelvic organ prolapse and stress incontinence.

Question 36

Describe the presentation of Atrophic vaginitis?

Answer 36

Symptoms

• There may be no symptoms.
• Dryness of the vagina is the most common symptom
• There may be burning or itching of the vagina or vulva.
• Dyspareunia.
• Vaginal discharge (usually white or yellow).
• Vaginal bleeding or postcoital bleeding.
• Urinary symptoms - eg, increased frequency, nocturia, dysuria, recurrent UTI, stress incontinence or urgency.
• Decreased arousal, desire and orgasm.

Signs

• External genitalia may show reduced pubic hair, reduced turgor or elasticity, and a narrow introitus.
• Vaginal examination may show:
  
  • Thin mucosa with diffuse erythema.
  • Occasional petechiae or ecchymoses.
  • Dryness.
  • Lack of vaginal folds.
  • Prolapse of urethra and/or vagina.

Question 37

What investigations should be done for Atrophic vaginitis?

Answer 37

• Investigations may not be necessary if the diagnosis is clear and there are no clinical features causing concern.
• Investigation may be needed to exclude other problems:
  
  • Any postmenopausal bleeding requires investigation.
  • If there is discharge or bleeding, an infection screen may be relevant (for vaginal infections or endometritis).
  • Other causes of recurrent UTI.
  • Screen for diabetes may be considered (uncontrolled diabetes can contribute to symptoms).
• Other possible investigations are:
  
  • Vaginal pH testing (using pH paper and sampling from the mid-vagina, not the posterior fornix). The result is more alkaline in atrophic vaginitis.
  • Vaginal cytology - can show lack of maturation of the vaginal epithelium, typical of atrophic vaginitis.
• Assessment tools may be useful in evaluating severity of symptoms and their response to treatment.

Question 38

What is the management of Atrophic vaginitis?

Answer 38

The principles of management are:

• Restoration of urogenital physiology.
• Alleviation of symptoms.

Non-hormonal

• Lubricants - Examples include Sylk, Replens and YES.
• Moisturisers

Hormonal

• HRT
• Topical oestrogen can make a big difference in symptoms. Options include:
  
  • Estriol cream, applied using an applicator (syringe) at bedtime
  • Estriol pessaries, inserted at bedtime
  • Estradiol tablets (Vagifem), once daily
  • Estradiol ring (Estring), replaced every three months

Topical oestrogen shares many contraindications with systemic HRT, such as breast cancer, angina and venous thromboembolism. It is unclear whether long term use of topical oestrogen increases the risk of endometrial hyperplasia and endometrial cancer. Women should be monitored at least annually, with a view of stopping treatment whenever possible.