Optimising medicines management in women’s health

What are the main roles of oestrogen in women?

• Physical changes associated with puberty in women

• Regulating the menstrual cycle

• Various roles in a healthy pregnancy

What other roles do oestrogen have in men and women?

• Sexual desire

• Erectile function

• Lipid metabolism

• Brain function

• Bone health

• Skin health

What is the role of testosterone in women?

development and maintenance of female sexual anatomy

physiology
sexual behaviour
Libido
physiological processes in the brain
muscle mass
bone strength,
cardiovascular health,
overall energy levels
quality of sleep

What mental functions does testosterone play in women?

Strengthens nerves in brain → Mental sharpness
Strengthens arteries to brain → reducing memory loss
Regulates serotonin levels and uptake to the brain
Stimulates dopamine

Definition Menopause?

the permanent cessation of menstruation resulting from the loss of ovarian follicular activity
Average UK 55

When is menopause diagnosed?

after 12 consecutive months without a menstrual period.
Usually occurs between the ages of 45 and 55

Define peri-menopause?

the transitional phase leading up to menopause, characterised by irregular menstrual cycles and symptoms due to fluctuating hormone levels.

What is the duration of perimenopause?

can begin several years before menopause and last until one year after the final menstrual period
Average 4 years

What percentage of women get menopausal symptoms?

80-90% , with 25% severe and debilitating

What happens to oestrogen during perimenopause and menopause?

Most produced by ovaries pre-menopause. Levels fluctuate and eventually decline

What happens to progesterone during perimenopause and menopause?

Levels decrease with the reduction of ovulation

What happens to testosterone during perimenopause and menopause?

25% produced in ovaries. Levels decline through menopause and stay low thereafter

What happens to FSH during perimenopause and menopause?

Levels increase due to loss of feedback mechanisms to the pituitary gland

What are the main categories of symptoms in menopause?

Vasomotor Symptoms
Menstrual Irregularities
Psychological Symptoms
Urogenital Symptoms
Urinary Symptoms:
Sleep Disturbances:
Joint and Muscle Pain:
Weight Gain:
Skin Changes:

What are the Vasomotor Symptoms symptoms in menopause?

Hot Flushes:
Night Sweats:

What are the Menstrual Irregularities symptoms in menopause?

Irregular Periods:
Amenorrhoea

What are the Psychological Symptoms symptoms in menopause?

Mood Changes
Cognitive Changes

What are the Urogenital Symptoms symptoms in menopause?

Vaginal Dryness:
Dyspareunia:

What are the Urinary Symptoms: symptoms in menopause?

Increased frequency, urgency, and risk of UTIs

What are the Sleep Disturbances symptoms in menopause?

Insomnia or disrupted sleep

What are the Joint and Muscle Pain: symptoms in menopause?

Generalized aches

What are the Weight Gain: symptoms in menopause?

around the abdomen

What are the Skin Changes: symptoms in menopause?

Thinning, dryness, loss of elasticity

Who can have a diagnosis with no lab test?

• Not had a period (amenorrhoea) for at least 12 months and are not using hormonal contraception.

• Often diagnosed retrospectively

• Or, symptoms in women without a uterus

Are over 45 healthy, symptoms

How is perimenopause diagnosed?

vasomotor symptoms and irregular periods; lab tests can be used to rule out other conditions

What are the possible differential diagnoses?

thyroid disorders,

depression,

or pregnancy
Premature Ovarian Insufficiency (POI) (if aged <40) and

early menopause (if aged <45)
When to measure levels if in NICE

What is the only test used to diagnose menopause?

FSH

Which groups of women would do a FSH test?

aged 40 to 45 years with possible menopausal symptoms, including a change in their menstrual cycle
aged under 40 years in whom menopause is suspected

What levels of FSH may indicate menopause?

>30 mIU/mL

What about oestrogen as a diagnostic?

Low levels may be observed but are not routinely measured for diagnosis

What should be consider before starting treatment?

Consideration to full history
Track and record symptoms
Lifestyle modifications
Then HRT
Treatment should be adapted as needed

What about SSRIs, SNRIs and clonidine?

Should not be routinely offered as first line for vasomotor symptoms

What are some non pharmacological treatment options?

Healthy diet,
Regular exercise,
Stopping smoking,
Drinking moderately,
Relaxation techniques
Cognitive Behavioural Therapy (CBT)

What should a healthy diet include?

low in saturated fat and salt and rich in calcium and vitamin D to strengthen bones

Why should women stop smoking?

as smoking has been shown to increase the risk of an earlier menopause and trigger hot flushes.
higher risk of developing osteoporosis and heart disease

Why should menopausal women reduce drinking?

alcohol increases hot flushes and is associated with an increased risk of breast cancer.

Why may CBT be useful?

effective option in improving hot flushes, nights sweats and other menopausal symptoms and can be considered in women who do not wish to take HRT or are unable to take HRT

What are the 2 different hormonal HRTs?

Oestrogen only Therapy
Combined HRT:

When would a woman have Oestrogen only HRT?

only ever used as monotherapy in patients without a uterus)

When would a woman have combined HRT?

for women with an intact uterus to prevent endometrial hyperplasia

What are the routes of admin for HRT?

Oral, transdermal, vaginal
Risk verses benefit

What is oestrogen available in?

patches, gels, sprays and oral tablets

What is progesterone available in?

‘Mirena’ IUD, oral tablets and combined patches

When is the non oral route of oestrogen preferred?

>60 years old and/or VTE risk factors e.g. FHx VTE or BMI >30

What is sequential HRT?

• Take oestrogen all the time and the progesterone at certain times of the month

• Have break through bleeds

• Max 1 year

When is continuous used?

Not when menstrating as will have break through bleeds the whole time

What is the dose of progesterone need decided by?

Dose needed depends on dose of oestrogen.

Why is progesterone needed if womb intact?

reduces risk of endometrial cancer by protecting womb from affects of oestrogen

What are the positives of body identical progesterone?

neutral affect on VTE risk and slightly lower breast cancer risk
Micronised progesterone (Utrogestran – a capsule)

Why is the transdermal route considered safer?

do not affect the risk of blood clotting or stroke at standard doses

What are treatments for Genitourinary syndrome of menopause (Gsm)?

Topical oestrogens - NOT HRT

What is the administration of topical oestrogens?

Local application to the vagina via vaginal ring, pessary or cream

Why do topical oestrogens not need progesterone?

• Little to no systemic absorption

• No need for endometrial protection with progesterone

• Vaginal oestrogen reduces UTI by 50-60%

What are the possible side effects of oestrogen?

Breast tenderness, breast enlargement, bloating, nausea, headache/migraine and leg cramps

What are the side effects of progesterone?

Fluid retention, breast tenderness, lower abdomen pain, backache, depression, mood swings, acne/greasy skin and headache

What percentage of women get unscheduled bleeding?

40%
Very common in first 6 months or 3 months after change

What can reduce risk of unscheduled bleeding?

HRT optimisation

What is the biggest risk factors of endometrial cancer?

BMI >40, genetic risk,

unopposed oestrogen for >6/12,

>5 years sequential HRT use in women >45 years,

inadequate progesterone dose alongside oestrogen HRT for >12 M

What are the minor risk factors of endometrial risk factors?

BMI 30-39
unopposed oestrogen for 3-6M,
inadequate progesterone dose alongside oestrogen HRT for <12M
Diabetes

What is the baseline age-related incidence of endometrial cancer?

in newly menopausal women 0.7% if aged 50-54; 1.2% if aged 55-59

What is risk of breast cancer related to in HRT treatment?

is related to treatment duration and reduces after stopping HRT
Combined is associated with increased risk

What does NICE recommend around the management of Cardiorisk with HRT?

Less than 10 years than LMP → benefits
Staying on is safer than stopping and starting
Use non oral is there are risks

What does NICE recommend around the VTE risk of HRT?

BMI > 30kg/m2 consider swapping to oestradiol patch/gel, ensure not on high dose norethisterone
Transdermal risk no greater than the population risk

CI HRT?

• Known or suspected oestrogen-dependent cancer

• Undiagnosed vaginal bleeding

• Untreated endometrial hyperplasia

• VTE or history of recurrent VTE, unless the woman is already on anticoagulant treatment

• Active or recent arterial thromboembolic disease

• Thrombophillic disorder or thrombophlebitis

• Untreated or unstable hypertension

• Active liver disease with abnormal liver function tests

• Acute Porphyria

• Pregnancy

• Dubin-Johnson and Rotor syndromes (monitor closely)

What are important counselling points?

Bleeding 3-6 months if over report
Short bleed on sequential HRT
Adherence
Not a contraceptive
Health screening

How long are women < 50 years of age – considered potentially fertile?

2 years after her last menstrual period

How long are women > 50 years of age – considered potentially fertile?

1 year after her last menstrual period

When should follow up be after initiation of HRT or change in therapy?

three months follow-up

When should follow up be once established on HRT?

at least annual review

What should a review/ follow up contain?

bleeding patterns;

type and dose of HRT;

on-going risk/benefit balance;

ensure patient attending National cervical and breast screening when invited,

advise self-checking breasts

encourage healthy lifestyle

When should stopping be considered?

continued for as long as benefits of symptom control and quality of life outweigh risks
Offer gradual reduction of HRT to limit recurrence of symptoms

What to do when symptoms not controlled?

Increase dose (within licensed dose range)

or change formulation (after persistence with treatment for at least 3 months)

What to do with patch irritation?

Try alternative brand or route

What do when interacting drugs?

Change to non-oral route. Intra-Uterine Systems are not affected

Examples of drug interactions with HRT?

Enzyme inducers lower the circulating levels of hormone e.g. barbiturates, phenytoin, carbamazepine.

Non hormonal?

• SSRIs/SNRIs:

• Clonidine:

• Gabapentin:

• Vaginal Moisturizers and Lubricants

What can SSRI/SNRIs be used for?

For mood symptoms and hot flushes (e.g., venlafaxine, fluoxetine).

What can Clonidine be used for?

An alpha-agonist that can reduce hot flushes.

What can Gabapentin be used for?

Can be effective for vasomotor symptoms.

What can Vaginal Moisturizers and Lubricants be used for?

For urogenital symptoms.

When testosterone be given?

a trial of conventional HRT is given before testosterone supplementation is considered
post-menopausal women who complain of low sexual desire (Hypoactive Sexual Desire Disorder; HSDD) after a biopsychosocial approach

Side effects of testosterone

: Excess hair growth, acne and weight gain which are usually reversible with reduction in dosage or discontinuation.