Menopause & HRT Flashcards
1
Q
What is menopause?
A
A retrospective diagnosis after a woman hasn’t had a period for 12 months. A permanent end to menstruation.
2
Q
How long after a woman’s final period is a diagnosis of menopause made?
A
12 months
3
Q
Average age of menopause?
A
51
4
Q
Define postmenopause
A
The period from 12 months after the final menstrual period onwards.
5
Q
Define perimenopause
A
The time around the menopause, where the woman may be experiencing vasomotor symptoms and irregular periods. Include the time leading up to the last period, and the 12 months after.
6
Q
Define premature menopause
A
Menopause before 40 years old. Result of premature ovarian insufficiency.
7
Q
What is the cause of menopause?
A
A lack of ovarian follicular function, resulting in changes in the sex hormones associated with the menstrual cycle:
- Oestrogen and progesterone are low
- LH and FSH are high, in response to an absence of a negative feedback from oestrogen
7
Q
Describe the levels of oestrogen and progesterone in menopause
A
Low
8
Q
Describe the levels of LH and FSH in menopause
A
High due to an absence of a negative feedback from oestrogen
9
Q
Describe how a decline in development of ovarian follicles leads to menopause
A
1) Begins with decline in development of ovarian follicles
2) Without growth of follicles, there is a reduced production of oestrogen (usually produced by granulosa cells that surround follicles)
3) As oestrogen falls in perimenopausal period, there is an absence of a negative feedback on the pituitary gland, and increasing levels of FSH and LH (oestrogen has a negative feedback effect on pituitary gland, suppressing LH and FSH)
4) Falling follicular development means ovulation does not occur (anovulation), resulting in irregular menstrual cycles
5) Without oestrogen, endometrium doesn’t develop, leading to a lack of menstruation (amenorrhoea)
6) Lower oestrogen also causes perimenopausal symptoms
10
Q
Describe the feedback of oestrogen on the pituitary
A
Negative feedback - reduces levels of LH and FSH
11
Q
Where is oestrogen produced?
A
Granulosa cells that surround follicles
12
Q
What causes perimenopausal symptoms
A
Lack of oestrogen
13
Q
What are some perimenopausal symptoms?
A
- Hot flushes
- Emotional lability or low mood
- Premenstrual syndrome
- Irregular periods
- Joint pains
- Heavier or lighter periods
- Vaginal dryness and atrophy
- Reduced libido
14
Q
What conditions can a lack of oestrogen increase the risk of?
A
- CVS disease and stroke
- Osteoporosis
- Pelvic organ prolapse
- Urinary incontinence
15
Q
When can a diagnosis of menopause be made without performing any investigations?
A
Can be made in women over 45 years old with typical symptoms
16
Q
When does NICE recommend considering an FSH test for menopause?
A
a) Women <40 with suspected premature menopause
b) Women aged 40-45 with menopausal symptoms or change in menstrual cycle
17
Q
How long should women under 50 use contraception for after the last menstrual period?
A
two years
18
Q
How long should women over 50 use contraception for after the last menstrual period?
A
1 year
19
Q
Does hormonal contraception affect menopause?
A
No - but can mask and suppress symptoms
20
Q
What contraceptive options are UKMEC 1 for women approaching menopause (i.e. good options)?
A
- Barrier methods
- Mirena or copper coil
- Progesterone only pill
- Progesterone implant
- Progesterone depot injection (<45 y/o)
- Sterilisation
21
Q
Side effects of progesterone depot injection?
A
- Weight gain
- Reduced bone mineral density (osteoporosis) – makes it unsuitable for women >45
22
Q
At what age does the progesterone depot injection become unsuitable?
A
> 45 y/o
23
Q
Management of menopause?
A
- No treatment
- HRT
- Tibolone – a synthetic steroid hormone that acts as continuous combined HRT (only after 12 months of amenorrhoea)
- Clonidine – acts as agonists of alpha-adrenergic and imidazoline receptors
- Cognitive behavioural therapy (CBT)
- SSRI antidepressants e.g. fluoxetine, citalopram
- Testosterone – can be used to treat reduced libido (gel/cream)
- Vaginal oestrogen cream or tablets – can help with vaginal dryness and atrophy (can be used alongside systemic HRT)
- Vaginal moisturisers e.g. Sylk, Replens, and YES
24
What is tibolone?
A synthetic steroid hormone that acts as continuous combined HRT (only after 12 months of amenorrhoea)
25
What hormones are given in HRT
- Oestrogen to alleviate symptoms
- Progesterone (in women who have a uterus)
26
Why must progesterone be given alongside oestrogen in HRT in women who have a uterus?
To prevent endometrial hyperplasia and endometrial cancer secondary to “unopposed” oestrogen.
I.e. endometrial protection
27
What HRT regime should women that still have periods go on?
Cyclical HRT, with cyclical progesterone and regular breakthrough bleeds
28
What HRT regime should postmenopausal women with a uterus and more than 12 months without periods go on?
Continuous combined HRT
29
What HRT regime can women without a uterus go on?
Oestrogen only HRT
30
Non-hormonal treatments for menopausal symptoms?
- Lifestyle changes such as improving the diet, exercise, weight loss, smoking cessation, reducing alcohol, reducing caffeine and reducing stress
- Cognitive behavioural therapy (CBT)
- Clonidine, which is an agonist of alpha-adrenergic and imidazoline receptors
- SSRI antidepressants (e.g. fluoxetine)
- Venlafaxine, which is a selective serotonin-norepinephrine reuptake inhibitor (SNRI)
- Gabapentin
31
What class of drug is clonidine?
Agonist of alpha-2 adrenergic receptors and imidazoline receptors in the brain
32
How is clonidine effective in menopausal symptoms?
It can be helpful for vasomotor symptoms and hot flushes:
- Lowers BP
- Reduces HR
33
When would clonidine be used in HRT?
Particularly where there are contraindications to using HRT.
34
Side effects of clonidine?
- Dry mouth
- Dizzines
- Fatigue
- Headaches
35
What can a sudden withdrawal from clonidine result in?
Rapid increases in blood pressure and agitation.
36
Patients may try alternative remedies for menopausal symptoms BUT these can have significant side effects and interact with other medications.
Ensure to ask about them in patient history.
Give some examples of alternative remedies
- Black cohosh
- Dong quai
- Red clover
- Evening primrose oil
- Ginseng may be used for mood and sleep benefits
37
Potential side effects of black cohosh?
may be a cause of liver damage
38
Potential side effects of dong quai?
may cause bleeding disorders
39
Potential side effects of red clover?
may have oestrogenic effects that would be concerning with oestrogen sensitive cancers
40
Potential side effects of evening primrose oil?
has significant drug interactions and is linked with clotting disorders and seizures
41
What are the 4 main indications for HRT?
1) Replacing hormones in premature ovarian insufficiency, even without symptoms
2) Reducing vasomotor symptoms such as hot flushes and night sweats
3) Improving symptoms such as low mood, decreased libido, poor sleep and joint pain
4) Reducing risk of osteoporosis in women under 60 years
41
In women under 60 years, the benefits of HRT generally outweigh the risks.
What are the key benefits to inform women of?
Improved vasomotor and other symptoms of menopause (including mood, urogenital and joint symptoms)
Improved quality of life
Reduced the risk of osteoporosis and fractures
42
Women may be concerned about the risks of HRT. It is crucial to put these into perspective.
Who are the risks of HRT more significant in?
1) older women (the risks are NOT increased in women under 50 years compared with other women their age)
2) longer duration of treatment
43
What are the principal risks of HRT?
1) Increased risk of breast cancer (particularly combined HRT – oestrogen-only HRT has a lower risk)
2) Increased risk of endometrial cancer (but there is NO risk in women without a uterus)
3) Increased risk of venous thromboembolism (2 – 3 times the background risk)
4) Increased risk of stroke and coronary artery disease with long term use in older women (but NO increased risk with oestrogen-only HRT)
5) The evidence is inconclusive about ovarian cancer, and if there is an increase in risk, it is minimal
44
How can the risk of VTE in HRT be reduced?
by using patches rather than pills
45
Contraindications to HRT?
- Undiagnosed abnormal bleeding
- Endometrial hyperplasia or cancer
- Breast cancer
- Uncontrolled hypertension
- Venous thromboembolism
- Liver disease
- Active angina or myocardial infarction
- Pregnancy
45
Before initiating HRT, there are a few things to check and consider.
Give some examples
- 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
46
What are the 3 steps to consider when choosing the HRT formulation?
1. Do they have local or systemic symptoms?
a) Local symptoms: use topical treatments such as topical oestrogen cream or tablets
b) Systemic symptoms: use systemic treatment – go to step 2
2. Does the woman have a uterus?
a) No uterus: use continuous oestrogen-only HRT
b) Has uterus: add progesterone (combined HRT) – go to step 3
3. Have they had a period in the last 12 months?
a) Perimenopausal: give cyclical combined HRT
b) Postmenopausal (more than 12 months since last period): give continuous combined HRT
47
For local symptoms in menopause, what can be used?
Use topical treatments such as topical oestrogen cream or tablets
48
What are the 2 options for delivering systemic oestrogen in HRT?
1) Oral (tablets)
2) Transdermal (patches or gels)
49
49
50
51
52
Why is continuous combined HRT not used before postmenopause?
Can lead to irregular breakthrough bleeding and investigation for other underlying causes of bleeding.
53
What are the added benefits of mirena coil for HRT?
Mirena coil has the added benefits of contraception and treating heavy menstrual periods.
53
What are the three options for delivering progesterone for endometrial protection?
1) Oral (tablets)
2) Transdermal (patches)
3) 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.
53
How long is the mirena coil licensed for for endometrial protection?
The Mirena coil is licensed for four years for endometrial protection, after which time it needs replacing.
54
What is a progestogen?
Refers to any chemicals that target and stimulate progesterone receptors
55
What is progesterone?
The hormone produced naturally in the body
56
What is a progestin?
Synthetic progestogens
57
What are the 2 significant progestogen classes used in HRT?
C19 and C21 progestogens - referring to the chemical structure and number of carbon atoms in the molecule.
58
What are C19 progestogens derived from?
Testosterone
59
Examples of C19 progestogens?
norethisterone, levonorgestrel and desogestrel
60
Effect of C19 progestogens? What side effects may they be helpful with?
Are more “male” in their effects; may be helpful for women with reduced libido.
61
What are C21 progestogens derived from?
Progesterone
62
Examples of C21 progestogens?
progesterone, dydrogesterone and medroxyprogesterone
63
Effect of C21 progestogens? What side effects may they be helpful with?
Are more 'female' in their effects.
These may be helpful for women with side effects such as depressed mood or acne.
64
What is the best way of delivering oestrogen? Why?
Patches - due to reduced risk of VTE
65
What is the best way of delivering progesterone? Why?
IUD e.g. Mirena coil
The coil has the added benefits of contraception and treating heavy menstrual periods. Additionally, women will not experience progestogenic side effects.
66
What is tibolone?
a synthetic steroid
67
What receptors does tibolone stimulate?
Oestrogen and progesterone receptors.
Androgen receptors (weakly)
68
The effects on androgen receptors mean tibolone can be helpful for menopause patients with which symptom?
Reduced libido
69
How is tibolone used in HRT?
Tibolone is used as a form of continuous combined HRT.
70
Which women can use tibolone in HRT?
Women need to be more than 12 months without a period (24 months if under 50 years).
71
How are female testosterone levels impacted in menopause?
It is naturally present in low levels in women. Menopause can be associated with reduced testosterone
72
Impact of reduced testosterone in menopause?
Low energy and reduced libido (sex drive).
73
Testosterone can be given in menopause but is usually initiated and monitored by a specialist.
How is it given?
Via transdermal application (gel or cream)
74
How long before major surgery should oestrogen-containing contraceptives or HRT be stopped?
4 weeks before major surgery
75
Oestrogenic side effects of HRT?
Nausea and bloating
Breast swelling
Breast tenderness
Headaches
Leg cramps
76
Progestogenic side effects of HRT?
Mood swings
Bloating
Fluid retention
Weight gain
Acne and greasy skin
77
How can progestogenic side effects be avoided altogehter in HRT?
Mirena coil for endometrial protection
78
What is premature ovarian insufficiency?
menopause before the age of 40 years
79
What happens in premature ovarian insufficiency?
It is the result of a decline in the normal activity of the ovaries at an early age
80
Pathophysiology in premature ovarian insufficiency?
Characterised by hypergonadotropic hypogonadism.
Under-activity of the gonads (hypogonadism) means there is a lack of negative feedback on the pituitary gland, resulting in an excess of the gonadotropins (hypergonadotropism).
81
What will hormonal analysis show in premature ovarian insufficiency?
- Raised LH and FSH (gonadotropins)
- Low oestradiol levels
82
Causes of premature ovarian insufficiency?
Idiopathic (the cause is unknown in more than 50% of cases)
Iatrogenic, due to interventions such as chemotherapy, radiotherapy or surgery (i.e. oophorectomy)
Autoimmune, possibly associated with coeliac disease, adrenal insufficiency, type 1 diabetes or thyroid disease
Genetic, with a positive family history or conditions such as Turner’s syndrome
Infections such as mumps, tuberculosis or cytomegalovirus
83
What genetic condition can premature ovarian insufficiency be associated with?
Turner's syndrome
84
Presentation of premature ovarian insufficiency?
Presents with early onset of the typical symptoms of the menopause.
- Irregular menstrual periods
- Lack of menstrual periods (secondary amenorrhea)
- Symptoms of low oestrogen levels, such has hot flushes, night sweats and vaginal dryness.
85
How is premature ovarian insufficiency diagnosed?
Can be diagnosed in women;
a) younger than 40 years with typical menopausal symptoms
b) plus elevated FSH.
86
What FSH levels are required to diagnose premature ovarian insufficiency?
Who are these difficult to interpret in?
The FSH level needs to be persistently raised (more than 25 IU/l) on two consecutive samples separated by more than four weeks to make a diagnosis.
The results are difficult to interpret in women taking hormonal contraception
87
What conditions may women with premature ovarian failure are at risk of?
Multiple conditions relating to the lack of oestrogen, including:
- Cardiovascular disease
- Stroke
- Osteoporosis
- Cognitive impairment
- Dementia
- Parkinsonism
88
Management of premature ovarian failure?
HRT until at least the age at which women typically go through menopause.
89
Do women with premature ovarian failure need contraception?
Yes - still small risk
90
What are the two options for HRT in women with premature ovarian insufficiency?
1) Traditional hormone replacement therapy
2) Combined oral contraceptive pill
91
Benefits of option of traditional hormone replacement therapy in premature ovarian failure?
associated with a lower blood pressure compared with the combined oral contraceptive pill.
92
Benefits of option of COCP in premature ovarian failure?
The combined pill may be more socially acceptable (less stigma for younger women) and additionally acts as contraception.
93
Does HRT before age of 50 increase risk of breast cancer?
No - as women would ordinarily produce the same hormones at this age.
94
How can the risk of VTE in premature ovarian failure be reduced?
Using transdermal patches (i.e. patches)
95
Most common cause of PMB?
Atrophic vaginitis
96
Management of atrophic vaginitis?
Vaginal oestrogen: cream, pessary, or estring
97
Can vaginal oestrogen for atrophic vaginitis be used alongside HRT?
Yes
98
Does vaginal oestrogen have the systemic risks of HRT?
No - only local effects
99
Risks of HRT?
- Increased risk of breast cancer
- Heart disease: if HRT started 10y post-menopause
- Blood clots (thrombosis): oral only
- Stroke: oral only
100
Benefits of HRT?
- Symptom improvement
- Reduces risk of osteoporotic fractures
- Reduced risk of CVD and stroke if started early enough
- Reduced risk of bowel cancer
- Improves mucles strength
- Emergent evidence about dementia
101
