Menopause and HRT Flashcards
What is the menopause defined as?
What is the perimenopause?
How is the menopause diagnosed?
after one year of amenorrhea
The perimenopause or climacteric is the phase encompassing the menopause
Diagnosed as:
• Serum FSH level > 30 IU/l on 2 separate occasions = ovarian failure (menopause)
Can test menopause via this but isn’t routine – just for special cases i.e. menopausal symptoms at wrong age etc (premature ovarian failure)
what is the average age of menopause?
52
Describe what happens to the ovaries and LH/FSH leading up to the menopause?
What happens to periods leading up to the menopause?
¥ Ovaries contain finite number of oocytes which decreases steadily from birth until depletion
¥ Ovaries become less responsive to LH/FSH in lead up to menopause
¥ FSH levels peak around time of menopause
¥ Loss of ovarian function leads to oestrogen depletion (oestradiol)
¥ Lack endometrial stimulation → amenorrhoea
FSH rises more and more to ‘squeeze’ eggs out ovaries as oocytes get more deplete – FSH is highest around menopause
Periods – initially cycle shortens, then missed periods/irregular before eventual amenorrhoea
What are the 3 important estrogens in women?
- which is predominant in premenopausal women?
- which is predominant is postmenopausal women?
3 important oestrogens in women: oestradiol, oestriol & oestrone
υ Oestradiol (E2) is predominant in premenopausal women: produced by the ovaries
υ Oestrone (E1) is predominant in postmenopausal women : produced by peripheral conversion of androgens in the adipose tissue
E1 is less biologically active than E2, thus postmenopausal women suffer the symptoms
What are the acute symptoms of the menopause?
- vasomotor
- general
- psychological
Vasomotor (affects majority of women):
Hot flushes (smoking and high BMI worsens this)
Nights sweats
General Headache Fatigue Insomnia Arthralgia Dizziness
Psychological Poor memory Loss concentration Irritability Low mood Anxiety Reduced libido
Describe the medium term symptoms of the menopause?
- vaginal
- general
- urinary tract
Vaginal Dryness/itch/burning Dyspareunia Sexual dysfunction Prolapse
General
Dry skin
Hair thinning
Urinary tract Urinary frequency/nocturia Urgency Stress/urge incontinence Recurrent UTI (oestrogen depletion in skin in urogenital tissues)
What are the three long term consquences of the menopause?
-Cardiovascular disease
-cerebrovascular disease
(Oestrogen reduces LDL, increases HDL, reduces cholesterol deposition and fat distribution)
-osteoporosis
What 4 management strategies exist for the menopause?
To minimise symptoms and reduce risk long term consequences:
- Lifestyle measures – healthy diet, regular exercise, stop smoking
- Oestrogen-based therapy (HRT)
- Non oestrogen-based therapy
- Alternative/complementary medicine
What different preparations of HRT exist?
Oestrogen Only HRT (tablet, patch, gel, implant) (for those with hysterectomy or mirena coil)
Combined HRT: oestrogen + progestogen (tablets/patch)
Sequential – perimenopausal
Continuous – postmenopausal, ‘bleed-free’
If give perimenopausal continuous estrogen and progesterone = irratic bleeding
(ovaries are still producing some estrogen)
Women with a uterus require addition of a progestogen for endometrial protection (if have mirena coil can give estrogen only)
Sequential combined HRT:
- who is this used in?
- what hormones are given when?
- how is this given?
- what is the effect of progesterone?
- is this a method of contraception?
Oestrogen for 28days
Progesterone for 10-14days
Used for:
in peri-menopausal women with uterus
Single named product available as patch/tablet or combine two different preparations
Progestogen protects the endometrium and leads to a regular bleed
NOT a contraceptive
Mimics normal menstrual cycle, oestrogenic proliferation of endometrium followed by shedding in 2nd half cycle
Continuous combined HRT:
- who is this used in?
- what hormones are given and when?
- how is this given?
- what happens to periods?
Used in:
-post menopausal women with a uterus
Hormones:
-estrogen and progesterone for 28days
Single named products available as tablets/patches
No monthly bleed (after 1st 6 months)
The Mirena is now licensed for use with Oestrogen only HRT for 4 years. The advantage is that it can be used in younger women to induce a no-bleed regime
When is sequential HRT started and how long is the maximum duration of this?
Started when required in perimenopausal women (may still have periods)
Prolonged use can increase the risk of endometrial cancer (↑ RR 1.3 to 2.9 after 5 years, 0.2 with CC*); max duration 5 years
When is continuous combined HRT started or when is it recommended to switch from sequential to combined?
Started:
- 1 year after the LMP or aged 54
- if under 54, sequential HRT for 2 years then switch to CC HRT
Why is sequential HRT used in those under 54?
At age 54 80% of women will have cessation of ovarian function. Need ‘steady’ levels both hormones to achieve thinning endometrium.
Younger perimenopausal women may still have some endogenous ovarian hormone activity causing irregular bleeding/loss endometrial protection.
What HRT is used for vasomotor, psychological and libido problems?
Tibolone:
- Alternative to CC HRT (postmenopausal women)
- Synthetic steroid → weak oestrogenic, progestogenic and androgenic properties
Tibolone:
- what does this reduce the risk of?
- what has this got a slightly increased risk of?
Reduced risk of:
- Conserves bone mass and reduces risk fractures (not hip)
- reduced risk of breast cancer, similar to estrogen only HRT (however this is less than CCHRT)
Increased risk of:
- The risk: benefit ratio similar to HRT in women under 60, but over 60 increased risk of stroke
- slightly increased risk endometrial cancer
What HRT can be used to help general feeling of well being and improve libido?
-when is this used?
Testosterone:
- Used following natural menopause or bilateral oophrectomy along with systemic oestrogens (as an adjunct therapy to HRT)
- Available as 50mg/100mg implant or Intrinsa® patch releasing 300mcg/24 hours in UK
- Safety and efficacy beyond 1 year not known but trials on going and none discontinued so far due to adverse events
(ovaries are no longer producing testosterone)
What is given for women with vaginal and bladder symptoms who don’t want/need systemic HRT?
Local estrogen preparations:
- Vaginal creams, tablets and rings are available
- Low systemic absorption therefore addition progestogen for endometrial protection not required
- Licensed for long term use as needed
If a woman is on HRT, what is advised for health promotion/disease prevention?
- Annual BP checks
- Regular breast self-examination
- Cx smears every 3 yrs 25-49 then every 5 years 50-64
- Mammography every 3 years aged 50-64
- PMB/irregular bleeding pattern?
What are two main benefits of HRT?
Colorectal cancer
HRT reduces the risk of colorectal cancer:
-This is likely to be the anti-oxidant effect of oestrogen
Osteoporosis:
- Used in prevention and treatment
- Reduced risk of osteoporotic fractures with HRT in RCTs
- Not used 1st line in older women as a treatment for osteoporosis because less risky alternatives e.g. bisphosphonates – only use if symptomatic
What are the 5 risks of HRT?
- Breast cancer
- Venous thromboembolism
- Stroke
- Endometrial cancer
- Ovarian cancer
Breast cancer risk of HRT:
- which women are at risk of breast cancer due to HRT?
- which HRT has the highest risk?
- does the risk return to normal after stopping?
The risk is increased in women who take HRT for several years (cf. Alcohol, nulliparity, high BMI)
Combined HRT has the highest risk
For oestrogen-only HRT the risk is lower/absent
Risk increases with duration of use and returns to normal within ~5 years of stopping
Higher age + longer use = higher risk
VTE in HRT:
- which HRT is this risk assoc. with?
- when is this most common?
- what can be done if the patient has risk factors for HRT?
Oral HRT has been associated with an increased risk of VTE in RCT’s and observational studies.
Higher with combined HRT than oestrogen-only
More common in the first year of use
Risk may be lowered by transdermal route/changing progestogen - If woman has risk factors for VTE - give transdermal preparation
Stroke and HRT:
- who has a greater risk of stroke?
- which HRT puts patients more at risk?
In RCT’s HRT increased the risk of stroke (mostly ischaemic) compared with placebo
Older women have a greater absolute risk of stroke
Risk may depend on oestrogen dose
No significant difference between E2 only/combined preparations
Endometrial cancer and HRT:
- which HRT increases this risk the most?
- what is this risk dependant on?
- how is this risk reduced/eliminated?
Use of oestrogen-only HRT in women with uterus substantially increases the risk of endometrial hyperplasia/carcinoma
Dependent on dose/duration
Risk reduced with sequential HRT and eliminated with CC HRT
Ovarian cancer risk and HRT:
-does this risk go back to normal after stopping?
Observational studies suggest that long-term use of all HRT’s may be associated with a small increased risk
Returns to baseline a few years after stopping
What is used for hot flushes if HRT isn’t an option due to personal preference/other?
Clonidine – no firm evidence in clinical trials but some women get benefit for ‘hot flushes’
-Alpha-2-agonist
SSRIs (selective serotonin reuptake inhibitors) e.g. fluoxetine – as above: May act on thermogenic centres in the brain thus providing relief from hot flushes
SNRIs (serotonin and noradrenalie reuptake inhibitor) e.g. venlafaxine – as above
Gabapentin - occasionally tried
what dietary therapy can be used for menopausal symptoms?
Phytoestrogens are plant substances that have effects similar to oestrogen
Isoflavones: red clover soy beans soy products legumes
Lignans:
whole cereals
oilseeds
cereals
berries
What other alternative remedies exist for HRT?
Herbal methods
E.g. Black cohosh, Evening primrose, Ginseng, Ginkgo
Complementary therapies – Homeopathy, Acupuncture, Reflexology, Aromatherapy, Magnetism
None of these have been definitively proven to be beneficial and drug interactions can occur
Premature ovarian failure: what are the causes:
- chromosome abnormalities
- enzyme deficiencies
- autoimmune disorders
- chemo/radiotherapy
- surgery
- infection
Cessation of menses and complete/partial loss ovarian activity before the age of 45
-chromosome abnormalities
Turner syndrome (45XO)
Fragile X syndrome
Trisomy e.g. Downs syndrome
-enzyme deficiencies
Galactosaemia
17α-hydroxylase
Cholesterol desmolase
- autoimmune disorders:
- Associated endocrine conditions e.g. Hypothyroidism, Addison’s, DM
- Other non-endocrine associations
e. g. Crohns, vitiligo, SLE, RA, ITP, PA - Polyglandular failure syndrome
-chemo/radiotherapy
Hodgkins/non-Hodgkins lymphoma Myeloid leukaemia
Breast Ca
-surgery
Bilateral oophrectomy
Hysterectomy/UAE (reduce ovarian reserve)
-infection
Tuberculosis
Mumps
What is the treatment for premature ovarian failure
Hormone replacement required to keep tissues healthy and reduce long term complications
HRT (higher doses) or COCP (optional PFW) to age 52
Testosterone as patch or implant
Additional vaginal oestrogen may be needed
Risks at this age are due to non-use of HRT rather than use (on HRT same risk as age-equivalent population for breast Ca, VTE etc)
