HRT and the Menopause Flashcards
Why would you expect during menopause for there to be an increase in the number of UTIs?
There are two possible reasons for an increase in UTIs:
1) The vaginal tissue thins, making it more prone to infection (reduce in the natural barrier defence)
2) Women may experience difficulty emptying their bladder, which again increases risk of infection
Aside from recurrent UTIs, what are some of the other urinary symptoms associated with menopause?
Dysuria
Increase in the frequency and urgency of passing urine
Urinary incontience
What is the mean age of menopause occuring in the UK?
51
When can menopause actually be determined?
Following 12 months of spontaneous amenorrhea (absence of menstrual periods for a year) as a result of loss of follicle activity.
Describe the hormone changes that occur during the menopause.
By the age of menopause the number of eggs within the ovaries has significantly decreased meaning that the overall follicular activity begins to decline, stimulating a decrease in estrogen level. Due to the drop in estrogen there is then no negative feedback cycle acting on the pituitary to regulate FSH and LH levels and therefore they continue to rise.
The decline in which hormone is responsible for the symptoms associated with the menopause?
Decline in estrogen
How can some women still conceive during the menopause?
Despite levels of estrogen dropping during the menopause meaning that the negative feedback cycle is no longer established and FSH and LH are able to rise, often the LH level can remain relatively stabilised for some time and meaning that conception is possible.
What are the three stages of the menopause and what is the average associated with each stage?
Perimenopausal - usually lasts about 4 years starting at the age of around 47.5 years
Menopause - mean age is 51 years
Postmenopausal - 80% of women by the age of 54
What is the defining symptom that determines whether a women is in the perimenopause or menopause?
The symptoms associated with the perimenopause and menopause are generally the same (due to the drop in estrogen) however during perimenopause the women usually first has menstrual abnormalities such as periods being more irregular (longer or shorter cycles), and usually heavier cycles. Menopause is the time in which periods cease and then postmenopausal is the time period after which a women has not had a period for 12 months.
What is the percentage of women that do not undergo a perimenopausal transition?
About 10% of women their periods, instead of becoming more irregular, just stop abruptly
What age is classed as a premature menopause?
If a women’s periods stop before the age of 40
What types of risks are associated when a women undergoes a premature menopause?
Increased risk of osteoporosis
Increased risk of cardiovascular disease (heart attack, stroke etc).
What percentage of post-menopausal women seek help for their symptoms?
50%
What are some of the short term symptoms associated with the menopause, aside from changes in the menstrual cycle?
Sexual dysfunction (dyspareunia, vaginal dryness, reduced libido)
Depression
Sleep disturbances
Mood changes
Irritability
Joint and muscle pain
Vasomotor symptoms (night sweats, hot flushes, palpitations)
Recurrent UTIs
Urinary incontinence
What percentage of women during menopause experience vasomotor symptoms?
80%
What can urinary incontience during the menopause lead to?
Utheral syndrome which is defined by the symptoms:
Dysuria (pain on passing urine)
Increase in the frequency and urgency of passing urine
What are some of the positive effects of associated with estrogen?
Estrogen has positive effects on:
Increasing and protecting bone density
Positive effect on blood lipid profile
Positive effect of coagulation and fibrinolytic pathway
Briefly describe the role of estrogen in bone metabolism?
Estrogen increases bone density by promoting the activity of osteoblasts (bone forming cells) and reduces the number and activity of osteoclasts (bone degrading cells).
What age does peak bone mass occur?
Between the ages of 30 and 35
What age in women does the rapid deterioration of bone density occur?
In the five years after menopause as the protective effects of estrogen is no longer present (due to the decline in menopause) in maintaining/ increasing bone density.
What is meant by the blood lipid profile?
A blood lipid profile simple means the level of lipids in your blood. There are two types of lipids cholesterol and triglycerides.
What are some of the exerted cardio protective effects of estrogen in pre-menopausal women?
Estrogen specifically E2 mediates a range of cardioprotective effects such as reducing reactive oxygen species (ROS), oxidative stress and fibrosis whilst increasing angiogenesis and vasodilation all of which reduces the cardiovascular risk in premenopause.
What is estrogen’s role in the coagulation and fibrinolytic pathway?
Estrogen increases fibrinogen and the activity of coagulation factors whilst decreasing the concentration and activity of anti-coagulant proteins.
Which demographics often experience the complications associated with estrogen and why?
Those taking combined hormonal contraceptives.
Estrogen promotes coagulation and this can result in the clinical complication and side effect of the combined hormonal contraceptive, venous thromboembolism.
By understanding the protective effects of estrogen, what are some of the clinical complications that arise alongside menopause?
Osteoporosis (loss of calcium from the bones, increasing risk of fractures), resulting in fractured neck of the femur.
Myocardial infarction
Cerebrovascular accident
Why are strokes more commonly seen in the post-menopausal era in comparison to the pre-menopausal era?
Menopause is associated with an increase in multiple stroke risk factors.
These risk factors include:
Increase in abdominal obesity
Increase in triglycerides
Increase in total cholesterol and LDL cholesterol
Decrease in HDL cholesterol
Increased fasting glucose and other measures of insulin resistance
Increased BMI
Increase in blood pressure
What is the mnemonic for the remebering symptoms associated with menopause?
Amenorrhea
Blood pressure
Cholesterol
Depression
Emily’s UTIs
Fractures
Gain in weight
Hot flushes
Insulin resistance
Joint muscle pain
Which women are indicated HRT estrogen and progesterone and why?
Women with an intact uterus, progesterone prevents the over-stimulation of the endometrium associated with estrogen due to the increase risk of endometrial cancer.
Which HRT is indicated for a woman after a hysterectomy?
Estrogen only, there is no endometrium to over stimulate
What are some examples of naturally occuring estrogens used in HRT?
Estradiol
Estrone
Conjugated oestrogens (equine)
What is the main aim of oestrogen therapy?
To restore the natural estrogen levels pre-menopausal and therefore continue the negative feedback cycle with FSH and LH.
Why are naturally occuring estrogens used in HRT rather than synthetic HRTs?
Synthetic HRTs are x200 more potent, and therefore the risk of using them would outweigh the potential benefits (raised blood pressure, blood lipid profile etc). Remember use in HRT is just for the relief of symptoms, in contraception it is to prevent pregnancy, so the benefit is greater than the risk.
Also the generation that would potentially be using these HRTs are 10-30 years older and so the cardiovascular risk increases with age.
Can HRT protect against pregnancy?
Natural estrogens used in HRTs are x200 times less potent than the synthetic estrogens used in treatment of HRT. These estrogens are simply for relieving symptoms associated with estrogen defiency and restoring natural levels and do not provide protection aganist pregnancy.
When are women still considered potentially fertile?
For two years after their last period if they are aged under 50 (I think if they went through menopause under the age of 50 / menopause started under 50) or
For one year after their last period if they are aged over the age of 50
How would you advice and recommendations differ if a 48 year old women presented to the Pharmacy wanting some medication for menopause relief but also a contraceptive to if a 55 year old woman made the same request and why?
Women under the age of 50 can be given a low dose combined oral contraceptive which provides relief of menopausal symptoms and also effective contraception.
However women over the age of 50 have to be recommended separate non-hormonal contraception and HRT due to the risk associated with using combined oral contraceptives in over 50s.
What are the specific risks of using combined oral contraceptives in the over 50s (3)?
Raised blood pressure
Adverse lipid profile
Abnormal blood clotting
What is the minimum requirement of progesterone use in HRT?
At least every 10 days in every 28 days cycle
Which progesterones are used in treatment of HRT?
Artifically occuring progesterones as the oral absorption of natural progesterones are very low.
Normally see the less androgenic progesterones used in the treatment such as:
Dydrogesterone
Medroxyprogesterone acetate
What are some examples of more androgenic progesterones?
Norethisterone
Levonorgestrel
What are some of the routes of HRT available?
Oral
Transdermal (Patch, gel and spray)
Vaginal (Ring and cream)
Implant
When is cyclic/sequential HRT recommended?
Those taking combined HRT (Estrogen and progesterone) with menopausal symptoms but are still having their periods.
What are the two types of cyclic HRT?
Monthly HRT – you take oestrogen every day, and take progestogen alongside it for the last 14 days of your menstrual cycle
3-monthly HRT – you take oestrogen every day, and take progestogen alongside it for around 14 days every 3 months
When is monthly HRT recommended?
Still have regular periods
When is 3-monthly HRT recommended?
Those with irregular periods but are still having a period at least once every 3 months
When is the continuous combined HRT recommended?
Continuous combined HRT is usually recommended for women who are postmenopausal, have not had a period in a year. May have irregular bleeds for 6 months
Which oral HRT do you take a break and which do you take continously?
7 day interval:
Tricyclic scheme, 7 day placebo after 3 months
No interval:
Cyclic
Continuous
Estrogen only
What is the benefit of using the transdermal route of HRT administration?
More consistent HRT plasma concentration, reducing diurnal variation of HRT
Produces a more natural physiological
oestradiol:oestrone ratio
Bypasses first-pass metabolism and has less effect on clotting factors produced by the liver
Smaller dose
Considering the benefits of transdermal HRT administration, what is the reduced clinical complications?
Avoids first pass metabolism and reduced effect on clotting factors and therefore the risk of venous thromboembolism is reduced.
When does NICE specifically recommend use of transdermal patches for HRT?
First line treatment for women at a greater risk of developing VTE such as:
Previous history of VTE
Family history of VTE
BMI greater than 30
When is vaginal oestrogen recommended?
It is used as monotherapy when the vaginal symptoms (vaginal dryness, pain during sex) and or bladder symptoms dominate (dysuria, urinary incontinence, urethral syndrome) or in combination to systemic HRT (they have additional symptoms)
What are some examples of vaginal oestrogens?
Vaginal tablets (e.g. Vagifem®)
Ring (e.g. Estring®),
Creams or gel (e.g. Ovestin®, Gynest®), Pessaries
When is the OTC Vaginal estrogen tablet Gina indicated?
For vaginal atrophy due to oestrogen deficiency in postmenopausal women >50yrs who have not had a period for at least one year
What are the directions for Gina vaginal tablet?
One vaginal tablet daily for 2 weeks then twice weekly
When is the systemic HRT most commonly used?
If a patient presents primarily with the vasomotor symptoms and other symptoms (other than vaginal or bladder) associated with HRT.
Aside from relief of symptoms associated with the menopause when else is systemic HRT licensed?
Prevention and treatment of osteoporosis
What are some examples of systemic HRT?
Tablets
Patches (e.g. Evorel®)
Gel (e.g. Oestrogel®,Sandrena®)
Spray (e.g. Lenzetto®)
Implants (unlicensed)
If a woman was taking HRT for the relief of vasomotor symptoms, how long should they be prescribed the medication?
For 2-3 years with a review at 3 months initially and then an annual review.
What are the main side effects associated with HRTs? (what does it increase the risk of)
Increase in breast cancer
Increase risk of stroke
Increase risk of endometrial cancer
Risk of VTE
What adjustments should be made if HRTs are required for women over the age of 60?
Should be given at lower doses
Preferably trans-dermal route
What are some of the side effects associated with HRT due to estrogen?
Nausea and vomitting
Abdominal cramping and bleeding
Weight gain
Breast tenderness and enlargement
Pre-menstrual symptoms
Fluid retention
What are some of the side effects associated with HRT due to more androgenic progesterones?
Greasy skin and hair
Tend to off-set some of the protective effect of oestrogens on lipid profile
What are some of the side effects associated with HRT due to less androgenic progesterones?
Abdominal bloating
Mood changes such as irritability, depression
Breast tenderness
If a woman came into the pharmacy to complain about experiencing some of the side effects associated with HRT after a week, what would you recommend?
Normally the symptoms are transient and therefore try to tolerate for about 3 months before considering coming off them.
What are the most common reasons for non-compliance?
Side effects
Monthly bleeds now back (tricyclic reinstates monthly bleed)
Weight gain
Why did HRT popularity decline in the early 2000s?
The Women’s Health Initiative Study published an article on the increased risk HRT has on the development of VTE, breast cancer, cardiovascular events, stroke etc
What did the Cochrane Collaboration systematic review conclude about HRT use?
Does not prevent dementia or CVD
However does prevent osteoporosis
What did the recent publishings find about HRT?
Does increase the risk of breast cancer
What are some of the benefits of HRT?
Relief of short term symptoms associated with the pre and post menopausal eras such as:
Hot flushes and sweats (including night sweats)
Headaches
Urinary and vaginal symptoms
Mood changes and loss of libido
Thinning of the skin, brittle nails, hair loss
Aches and pains
What is one symptom associated with the menopause that HRT does not provide relief from?
Menstrual abnormalities as HRT can introduce unnatural menstrual cycles
What is the main long-term symptom of menopause that HRT reduces?
Osteoporosis as estrogen rebalances the bone formation and degradation by promoting osteoblasts activity and limiting osteoclast activity.
Does HRT reduce osteoporosis risk long-term?
Only as long as you are taking HRT, therefore consider switching to bisphosphonates once HRT is no longer recommended.
When is the risk of VTE greatest when using HRT?
Within the first year of use
Which types of HRT increase the risk of breast cancer?
All systemic types of HRT increase the risk of breast cancer after a year of use
Combined HRT have shown to have a greater risk than estrogen only, especially if taken continously
Does local vaginal estrogen increase the risk of breast cancer?
No
When does the risk of breast cancer reduce after stopping HRT?
Risk reduces after stopping but excess risk remains for over 10 years compared to women who have never used HRT
Which type of HRT is associated with endometrial cancer?
Oestrogen only HRT if used with women with a uterus (therefore ensure addition of progesterone at least 10 days per 28 day cycle).
Risk completely eliminated if taken continuously
What is the risk of ovarian cancer associated with HRT?
With both types of HRT, diminishes a few years after stopping
Which type of HRT increases risk of stroke?
Both types
How do trends in CVD change before and after the menopause?
Pre-menopause, men have a higher incidence of CVD than women
Post-menopause, incidence for both is similar
When is HRT known not to increase the risk of CHD?
When it is started under the age of 60
In all cases it does not reduce the risk of CHD
Is HRT contraindicated in the presence of CV risk factors?
No as long as it is optimally monitored and managed (hypertension and hyperlipidemia management)
In both types of HRT describe the risk relationship with CHD?
Oestrogen alone ► no, or reduced, risk of CHD
Oestrogen + progesterone ►little or no increase in risk of CHD
What is the current MHRA safety advice regarding HRT?
Those with symptoms, the risk to benefit ratio is favourable for HRT use
Those without symptoms, the risk to benefit ratio is unfavourable for HRT use
If HRT is to be used it should be the minimum effective dose for the shortest duration possible
What is tibolone?
It is a Gonadomimetic (stimulates estrogen receptors) and has mixed oestrogenic, progestogenic and androgenic activity.
When is tibolone licensed?
Licensed for short-term treatment of symptoms and osteoporosis prophylaxis (2nd line)
What are the cautions associated with tibolone?
Same cautions/ contraindications as Oestrogen HRT
Which type of HRT associated symptoms is Clonidine particularly licensed for?
Vasomotor symptoms
What type of medication is Clonidine?
Centrally acting ꭤ-adrenergic agonist => possibly reduces noradrenergic activity in blood vessels
What is the dosage for Tibolone?
2.5mg once daily
What is the dosage for Clonidine?
50mcg twice daily increased if required to 75mcg daily after 2 weeks
What are some of the unlicensed medications for HRT?
Selective serotonin re-uptake inhibitors (Fluoxetine, Sertraline, Citalopram)
Gabapentin
Pregabalin
What are some of the alternative HRT medications?
St John’s Wort
Products containing phytoestrogens (plants containing natural estrogens) such as:
Black cohosh
Red clover
Are HRT alternatives effective?
No efficiacy or safety data as they have no undergone the same clinical trials as the conventional HRT medications
What are some of the interactions associated with Black Cohosh and Red clover?
Black Cohosh causes liver impairment whilst red clover contains coumarins and has known interactions with warfarin.
Due to containing estrogen also has possible oestrogenic effects (VTE).
What are the main interactions associated with St John’s Wort?
It is a CYP inducer and therefore will reduce the activity of drugs that are metabolised by CYP.
St John’s Wort must not be taken with:
SSRIs
Birth control pills.
Cyclosporine (medicine used in organ transplants)
Digoxin (heart medicine)
Some HIV medicines (including indinavir)
Some cancer medicines (including irinotecan, tyrosine kinase inhibitors)
Warfarin (blood thinner)
Also decrease efficacy of HRT so shouldn’t be taken together
