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Module 1.4 (Menopause) Flashcards

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1
Q

What age is early menopause?

A

40 to 45 years

Premature menopause: less than 40

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2
Q

How is menopaused diagnosed?

A

After 12 months of amenorrhea

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3
Q

Usual age of menopause?

A

From 45 to 55 years

> average 50 years

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4
Q

Why does menopause occur?

A

Menopause occurs because the ovaries run out of eggs

> Each ovarian follicle contains a single oocyte

> A female infant is born with ~300 000 ovarian follicles

> By ~37 years of age ~ 25 000 ovarian follicles

> At menopause few or none remain

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5
Q

What are some of the hormones that change due to loss of ovarian follicles?

A
  • Decrease ovarain hormones (oestrogen and progesterone)
  • Increased FSH
  • No acute change in androgens
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6
Q

What are some factors influencing menopause?

A
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7
Q

What does FSH and LH do?

A

FSH: Stimualtes follicles (contains egg) in ovaries to produce estrogen, when estrogen reaches a certain level –> brain signals pituitary to turn of FSH and produce LH

LH: LH then stimulates the ovarie to reduce egg from follicle = ovulation

> left over follicle produces progesterone and estrogen in preparation for pregnancy

> as estrogen and progesterone increase, FSH and LH drop. If pregnancy doesn’t occur, progesterone level falls and menstruation occurs.

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8
Q

What are some other methods in which menopause can occur?

A

Chemotherapy-induced & radiotherapy-induced menopause

  • Sometimes periods can stop, but can return after some months, depending on a woman’s age and the type of chemotherapy received

Surgery-induced

  • Removal of ovaries –> due to endometriosis or ovarian cancer ( can be prophylactic)
  • Hysterectomy = uterus removed –> don’t necessarily go straight into menopause if ovaries are not removed
  • Surgical menopause symptoms are liekly to be more severe
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9
Q

What does the arisal of menopause symptoms come from?

A

Many women will experience symptoms associated with a lack of oestrogen both in the perimenopausal and postmenopausal phase

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10
Q

What are symtpoms associated with lack of estrogen in menopause?

A

Vasomotor symptoms (VMS)

Psychological problems

General physical

Urogenital and sexual –> occur later. Loss of estrogen causes loss of collagen and elastin.

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11
Q

What are some vasomotor, psychological, general physical and urgoenital + sexual symptoms that are found in menopuase?

A
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12
Q

Is there are a age limit at which menopausal symptoms cease?

A

No

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13
Q

What are some things associated with hot flushes and night sweats that 85% of women experience?

A

Most troublesome in the year around the final menstrual period

Feeling of heat that usually starts in the chest and spreads upwards to the neck and head

  • Come and go
  • Seconds to minutes
  • Can be associated with sweating
  • Some experience simultaneous racing or pounding heartbeats
  • Many feel self conscious

Night sweats = night-time hot flushes with profuse sweating

> result in night awakenings and poor sleep

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14
Q

What do 50% of menopausal women experience?

A

Hot flushes and night sweats

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15
Q

Who is more likey get hot flushes?

A

Overweight and obese

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16
Q

For vasomotor symptoms, why are they often underestimated?

A
  • Negative impact on QOL
  • Length of time that they can last
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17
Q

What are some hot flush triggers?

A
  • Drinking alcohol
  • Consuming products with caffeine
  • Eating spicy foods
  • Being in a hot room
  • Feeling stressed or anxious
  • Wearing tight, heavy clothing
  • Smoking or being exposed to cigarette smoke
  • Bending over
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18
Q

Are there cogntivie changes in menopause? What is the actual reason behind this?

A

Evidence inconsistent

> Gradual decline in cognitive function expected as part of normal aging

  • However gradual decline in cognitive function expected as part of normal aging

Cognitive changes related to estrogen withdrawal include:

  • Deficits in verbal and working memory
  • Almost 75% of women having a subjective sense of memory loss
  • More likely associated with perceived stress or depressive symptoms than perimenopausal stage
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19
Q

Why does depression and anxiety occur in menopause?

A

Employment status may have changed, children may have left home, gain weight and higher BMI

  • Common and many risk factors, but hormones may play a role

> Dysregulation of 5HT & NA pathways due to changing oestrogen levels

  • Perimenopause -period of ↑ vulnerability

> ↑ risk with previous depressive episode

> Hot flushes not necessary to development of depression

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20
Q

Why does sleep disturbances occur in those with menopause?

A

Sleep quality deteriorates with aging

Menopause adds to issue

More women report sleep issues as they enter perimenopause

Factors include:

> hormones

> sleep hygeine

> mood disorders

–> can occur with or without night sweats

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21
Q

Why do urogenital problems arise in menopause?

A

Urogenital tissues –> sensitive to oestrogen and fluctuations in oestrogen during perimenopause

> fragile tissue and distressing symptoms

> 20-67% report moderate to severe symptoms of vaginal dryness or dyspareunia

Other symptoms: vaginal atrophy, narrowing and shortening of vagina and uterine prolapse

  • Urinary tract contains oestrogen receptors in urethra and bladder

> urinary incontinence

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22
Q

What are the adverse metabolic and health effects that occur because of fal in oestrogen

metabolic

cardiovascular

skeletal

A

Metabolic

  • Central abdominal fat deposition
  • Insulin resistance and increased risk of type 2 diabetes

Cardiovascular

  • Impaired endothelial function
  • Increased cholesterol

Cardiovascular disease leading cause of morbidity and mortality in post-menopausal women

Skeletal

  • Accelerated bone loss
  • Increased fracture risk
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23
Q

What are some other midlifehealth changes that occur in menopause?

A
  • Gain 2-5kg in menopause
  • Hair loss and hair growth
  • Skin changes with menopause = more wrinkling and dryness
  • During menopause estrogen levels decrease in the body breaking down bones at a faster rate –> may lead to osteoporosis
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24
Q

QOL in menopause?

A

As life expectancy increases so does the time women spend in menopause n

Currently a women can expect to live about 35% of her life in a post-menopausal state n

The quality of life of women entering menopause at earlier ages is thought be more adversely affected.

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25
Q

How is diagnsosis of menopause done?

A

Measuring hormone levels is unhelpful n

Diagnosis is via history taking (symptoms & changes in menstruation) n

Perimenopause lasts on average 4 to 8 years

One year after the last menstrual period a woman is considered post-menopausal

Symptoms scores can be a useful diagnostic tool

Differential diagnosis

  • Depression, anaemia and hypothyroidism are the most common conditions that mimic menopausal symptoms
  • SSRIs can cause hot flushes

If a patient is taking hormonal treatments it can be difficult to know when menopause is reached

> HRT doesn’t provide contraceptive cover. If women still ovulating there is a risk of pregnancy.

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26
Q

What are the treatment options for menopause?

A

Non-pharmacological measure (lifestyle)

Menopausal Hormone Treatments (MHT)

Non hormone pharmacological treatments

Complementary & alternative medicines (CAMs)

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27
Q

How to cope with menopausal symptoms?

A
  • Balanced and nutritious diet
  • Exercise
  • Relaxation

> women with healthy lifestyle appear to have fewer symptoms

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28
Q

Lifestyle changes for menopause?

A
  • Quit smoking
  • ≤ 2 standard alcohol drinks per day and two alcohol free days per week
  • Reduce caffeine
  • Keep cool/wearing layers
  • Avoiding triggers of VMSs
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29
Q

How reduce the risk of osteoporosis during menopause?

A

Aim for 1300mg of dietary calcium

Weight bearing physical exercise

Adequate Vit D – follow sun exposure guideline

Avoid excessive alcohol

Stop smoking

Avoid excessive caffeine

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30
Q

What are options for menopausal hormone treatments?

A

oestrogens

  • Conjugated oestrogens
  • Estradiol
  • Estriol

progestogens

  • Medroxyprogesterone n
  • Norethisterone n
  • Levonorgestrel IUD n
  • Micronised progesterone

TSECs

  • Bazedoxifene + conjugated oestrogens

tibolone

testosterone

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31
Q

How does oestrogen help with menopause?

A

Relieves symptoms including VMSs and urogenital atrophy caused by ↓ endogenous oestradiol production

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32
Q

How does progestogen help with menopause?

A

Reduces risk of endometrial cancer associated with unopposed oestrogen

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33
Q

Outline when and for what patients the below drugs are used for in menopause (MHT)

A) oestrogen only (unopposed oestrogen)

B) combined therapy (oestrogen and progesterone or bazedoxifene)

C) tibolone

A

A)

  • Estrogen taken continuously
  • Recommended in women post-hysterectomy (no uterus therefore not at risk of uterine cancer)

B)

  • Recommended in a women with uterus
  • Can be cyclical or continuous
  • *Bazedoxifene continuous only

> last menstrual period under 2 years or withdrawal bleeds or spontaenous bleeding. Use daily estrogen and progesterone.

C)

  • Suitable for postmenopausal women and women who have had a hysterectomy
  • Taken continuously
  • Alternative when progestogen-containing combined MHT is not tolerated
  • Also 1st line
34
Q

What are the benefits and risks for the following routes for MHT?

A) Oral

B) Intrauterine

C) Vaginal

D) Transdermal

A

A)

Risk of VTE and stroke higher than transdermal

B)

  • Levonorgestrel IUD instead of oral progestogen
  • Minimises systemic adverse effects
  • Can be prescribed in perimenopause → contraception; controls heavy bleeding

C)

  • Creams, pessaries
  • Progestogen not usually necessary
  • Investigate if any irregular, heavy bleeding

> some systemic absorption can occur

> estrogen for urogenital symptoms = 1st line, lowest effective dose,

D)

  • Gel or patch –> smaller doses of estrogen can be used
  • Avoids 1st pass effects – less side effects (e.g. nausea)
  • Breast cancer risk seems similar to oral
  • Can cause skin irritation
  • Risk of VTE and stroke lower
35
Q

How to initiate therapy for oestrogen?

A

Choice of oestrogen dose depend upon how a woman’s symptoms respond

  • Initiate therapy at a low or ultra low dose and then titrate upwards
  • Aavailable as tablets, patches, gels and intravaginal
36
Q

Oral dosage forms cheaper and preferred by women BUT transdermal (patches or gel) indicated for women with?

A
  • Malabsorption
  • Risk or past history of VTE or DVT, migraine, untreated hypertension, significant liver disease, smokers, overweight.
37
Q

When is intravaginal oestrogen therapy used (creams or pessaries) in menopause?

A

Used in women who symptoms are predominantly genitourinary

> urinary frequency

> dysuria

> vaginal atrophy

  • Also used in women or whom systemic oestrogen therapy is contraindicated or ineffective.
  • Safety not assured when used in vaginal dryness and history of breast cancer –> use non-hormal treatment like replense
  • Oestradiol > effect oestriol
38
Q

How long do women with intact uterus use long term intravaginal oestrogen?

A

12 day course of progestine very 6 or 12 months –> minimise risk of endometrial hyperplasia

39
Q

What causes most of the side effects from MHT?

A

Progestogens

40
Q

What do cyclical and continuous regiments of progestogens aim for?

A
  • Cyclical regimens aim for predictable bleeding pattern –> (10-14 days/month –> give women predictable monthly bleeding patterns)
  • Continuous regimens aim for no bleeding –> been in meopause for 2 years
41
Q

Irregular bleeding is common with all regimens particularly in the first 6 months for progestogens, true or false

A

True

> do ultrasound if longer than this and potentially hysterectomy

42
Q

AE of progestogens?

A

Breast tenderness, fluid retention, headache, depression, PMS like syndrome, acne may occur during progestogen phase of cyclical MHT

43
Q

How to manage adverse effects with progestogens?

A
  • Changing the progestogen
  • Reducing the dose (ensure endometrium is still protected)
  • Changing the route
  • Reducing the duration of progestogen to 10 days/month
  • Changing to a 3-monthly cyclical regimen
  • Changing to continous combined HRT if postmenopausal
44
Q

What forms do progestogens come in? What is a more natural form of progestogen?

A
  • Mostly taken orally
  • Norethisterone is the only preparation reliably absorbed via skin and is available in a combined MHT patch with estrogen
  • Micronised progesterone capsules are a form of “natural” or “ body identical” progesterone that is thought to be better tolerated

> more favourable breast safety profile

> neutral with CVD

> does not cause adverse mood effects

  • Levonorgestrol IUD is an alternative method to deliver progestogen directly to the endometrium
45
Q

What are tissue selective estrogen complexes (TSEC)? What are their effects on endometrium?

A
  • = SERM (selective estrogen receptor modulator) + oestrogen
  • E.g. bazedoxifene and conjugated equine oestrogen (Duavive®)

SERM exert different effects on different tissues

> agonists in some tissues

> antagonists in others

Effects one endometrium

  • First generation SERMs (e.g. clomiphene and tamoxifen) stimulate the endometrium
  • Newer SERMs (e.g. raloxifene and bazedoxifene) attenuate the proliferative effects of oestrogen on the endometrium
46
Q

How does duavivie work (oestrogen and bazedoxifine)? What are the good things about it? What is the indication?

A

Progestogen not required as bazedoxifene protects endometrium

  • Alleviates VMSs, ↓ vulvovaginal atrophy, improves BMD at hip and spine
  • Neutral effects on breast and endometrium

Indication

  • May be an option when progestogen MHT is not tolerated
  • Short term treatment for relief of menopausal symptoms
47
Q

What aare precautions for duavive?

A
  • New drug and unreported adverse effects or interactions may occur
  • Increased risk of VTE has been reported for both oestrogens and SERMs

> no additive effects observed on risk of VTE with TESC but true risk unknown

> contraindicated in a women with a history of VTE

> avoid in women at high risk of VTE

48
Q

When is tibolone used? What are its effects?

not a 1st line option

A

A synthetic steroid used as an alternative to combined MHT

  • Oestrogenic → vagina, bone and thermoregulatory centres = helps with hot flushes and bone loss
  • Anti-oestrogenic and progestogenic → breast and endometrium
  • Androgenic → ↓ total chol, HDL, LDL and triglycerides

> positive effects seen on mood and libido

49
Q

Who is tibolone unsuitable in?

A

Periomenopausal women

> risk of breakthrough bleeding

50
Q

What are the indications for tibolone?

A

Relief of menopausal symptoms – short term

2nd line for post-menopausal osteoporosis

51
Q

What are the risks/precautions for tibolone?

A
  • ↑ risk of breast cancer recurring
  • Doubles risk of stroke in women >60 years (those with HTN, stroke, AF and diabetes)
  • History of endometriosis
  • ? SLE
  • Surgery (immobilization)
  • Bleeding that persists >6 months

Avoid tibolone in older women esp >70 years old and those at increased risk of stroke

52
Q

What are the contraindications for tibolone?

A
  • Cerebrovascular disease n
  • Coronary artery disease n
  • Breast cancer n
  • Severe liver disease

2nd lined drug

53
Q

↑ risk of breast cancer and ↑ risk of endometrial hyperplasia –> does tibolone do this?

A

unclear evidence

54
Q

When is testosterone used in women? What is it used with?

A

Used in women with low testosterone who are experiencing lack or libido, lack of energy and ongoing fatigue

  • Used with oestrogen most often for lack of libido
  • No proven link between testosterone levels and symptoms
55
Q

What are the side effects of testosterone treatment?

A

Oily skin, acne, excessive facial and body hair, scalp hair loss, irritability, aggression

serious side effects: deepening of the voice, enlarged clitoris (both irreversible), ?breast cancer, ?endometrial stimulation, ?lipids

> No form of testosterone therapy for women is officially approved in Australia by the TGA

56
Q

If MHT is contraindicated, not tolerated, or not desired –> what to prescribe? What to consider for these other drugs?

A

1st line - venlafaxine 37.5 to 75mg daily (also desvenlafaxine)

2nd line - paroxetine 10 to 20mg daily (also escitalopram) –> interacts with tamoxifen. paroxetine/fluoxtine reduces efficacy of tamoxifen.

3rd line – gabapentin 100 to 300mg daily

4th line – clonidine 25 to 50mg twice daily

> Consider effectiveness, side effects, potential interactions

  • SNRIs, SSRIs → sexual dysfunction, drug interactions
  • Gabapentin → well tolerated
  • Clonidine → dry mouth, drowsiness and effect on BP
57
Q

What are some non-hormonal pharmacotherapeutic options for vaginal dryness? If ineffective, what to use?

A
  • Vaginal dryness
  • First line therapy is non-hormonal preparations

> moisturisers e.g. replens and sylk

  • If non hormonal, topical treatments are ineffective low dose vaginal oestrogens can be prescribed.
58
Q

What are bioidentical hormones? What are the concerns?

A

Refers to compounded products marketed as hormones identical to those produced in the body

> natural estrogen = estradiol

> natural progestin = progesterone

  • Concerns about safety of MHT saw an interest in bioidentical hormones develop
  • Lack of studies re safety

> Not endorsed by AMS

> Concern about lack of protection for endometrial hyperplasia and neoplasia

> Unregulated manufacturing conditions

> Salivary hormone testing unreliable

59
Q

Should topical progesterone be used in menopause?

A
  • Topical progesterone creams marketed to reduce osteoporosis
  • Have inadequate absorption
  • If used with oestrogen may result in serious unopposed oestrogenic side effects
60
Q

Is wild yam creams helpful in treating menopause?

A
  • Originally marketed as containing progesterone but this is not the case
  • Contain diosgenin which can be used to synthesise progesterone
61
Q

Is red clover (phytoestrogens) helpful in menopause?

A

Limited and conflicting research

  • May be useful for hot flushes, ?benefits on bone health, ?lower LDL cholesterol
  • May take 3 months daily use to ↓ hot flushes
62
Q

What are precautions for red clover?

A
  • Adverse effects – myalgia, headaches, prolonged menstrual cycle
  • In vitro studies suggest that red clover can inhibit CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4
  • May inhibit P-glycoprotein → reduces absorption of drugs
  • Red clover may have oestrogenic activity

> May interfere with hormonal contraceptives

> May ↑ risk of thrombosis due to estrogenic activity

> Methorexate toxicity with red clover?

63
Q

What is black cohosh used for in menopause?

A

Affects serotonin and dopamine

  • May cause improvements in VMSs
  • Unclear if helps hot flushes in breast cancer patients but no association between black cohosh and ↑ breast cancer risk
  • May alter efficacy and toxicity of cancer chemotherapy
  • May take 3 months of daily use to improve menopausal symptoms
64
Q

Black cohosh precautions and adverse efffects

A

May cause liver damage (rare)

  • Associated with cases of liver failure and hepatitis
  • Watch for symptoms of liver damage including: nausea, vomiting, loss of appetite, abdominal pain, diarrhoea, weightloss, tiredness and yellow discolouration of the skin or eyes
  • Other adverse effects: GI symptoms, rash dizziness, headache, tiredness, weight gain, breast pain, vaginal spotting, musculoskeletal complaints

> Black cohosh may harm the liver in some individuals. Use under the supervision of a healthcare professional.”

65
Q

What is the mainstay treatment for menopause? Why?

A

Oestrogen is the most effective treatment available for the relief of menopausal symptoms

  • Hot flushes
  • Vaginal dryness
  • Dypareunia

> need to consider patient individual risks and benefits

66
Q

What to do before starting oestrogen treatment?

A

Recommended to calculate cardiovascular risk and breast cancer risk prior to commencing therapy

  • Benefits outweighs risks if initiated for symptomatic women before the age of 60 years or 10 Years after menopause
67
Q

What to usse for hysterectomy patients

A

Oestrogen alone

68
Q

When to use combined oestrogen + progestin (or + bazedoxifene or + tibolone)?

A

In patients who have a uterus

69
Q

What is the goal of treatment for MHT? What were thy used for previously?

A

to relieve menopausal symptoms

  • In the past menopausal hormone treatments (MHT) were used to prevent

> coronary heart disease (CHD)

> osteoporosis

NO LONGER RECOMMENDED for disease prevention

> due to results of womens health initiative –> unfavourable risk/benefit profile of MHT for this use

70
Q

Increased in patient CV risk in MHT?

A

Yes

  • Need to assess patient CV risk before commencing MHT
71
Q

What do guidelines say about MHT and CV disease?

A
  • Risk not increased if MHT commenced under 60 years
  • Mortality from CV disease not increased
  • Presence of CV risk factors is not a contraindication to MHT
  • Oestrogen alone therapy is associated with no or ↓ risk of CV disease
  • Oestrogen + progestogen associated with little or no ↑ risk of CHD
  • Oral (but not transdermal) oestrogen is associated with a small ↑ in stroke risk (but baseline risk under 60 years is low)
72
Q

Evaluating CVD risk for MHT?

A
73
Q

What is associated with an increased risk of VTE? What to use instead?

A

Oral estrogen is associated with an ↑ risk of VTE (2-4 fold)

Absolute risk is small for women < 60 years old

–> individuals have different risk factors

  • Transdermal estrogen is preferred for women at increased risk of VTE, i.e. smokers, obese

> bypasses first pass metabolism

74
Q

Relationship between MHT and breast cancer?

A

The baseline risk of breast cancer for women around menopausal age varies from one woman to another

  • MHT with oestrogen alone is associated with little or no change in the risk of breast cancer
  • HRT with oestrogen and progestogen can be associated with an increase in the risk of breast cancer and in women without hystrecetomy
  • Any increase in the risk of breast cancer is related to treatment duration and reduces after stopping MHT.
75
Q

Postmenopausal women with a history of hormone-dependent cancer, need special consideration. Why?

A

Menopausal symptoms can arise because

  • Cancer treatments induce menopause
  • MHT is stopped with the diagnosis of cancer
  • Endocrine therapies commenced (eg tamoxifen, aromatase inhibitors)

> symptoms similar to natural menopause

> added psychological component of the woman’s response to her cancer diagnosis

  • Non hormone therapies may be helpful however paroxetine should be avoided in patients on tamoxife
76
Q

Does MHT help with osteoporosis? Which ones help?

A

Combination, tibolone, TSECS

MHT effective in the prevention of bone loss in postmenopausal woman

  • ↓ risk of hip, vertebral and other osteoporosis-related fractures in post-menopausal women
  • Only therapy to ↓ risk of fracture in women with low fracture risk (T-scores normal to osteopoenic)
  • However, ↓ fracture risk is lost a few years after stopping

> this is an issue because patients >70 need it as fracture risk is higher but wont be on because sx of menopause last until 65.

77
Q

When can MHT be initiated in post-menopausal women at risk of fracture or osteoporosis?

A

MHT can be initiated in postmenopausal women at risk of fracture or osteoporosis <60 years (or within 10 years of menopause)

78
Q

Why is MHT 2nd line treatment for fracture prevention >60 years?

A

Benefits dont outweight their risks such as VTE, stroke and breast cancer

79
Q

What is spontaneous menopause <45 years (esp<40 years) associated with?

A
  • ↑ risk CVD
  • ↑ risk of osteoporosis
  • ↑ risk affective disorders and dementia
80
Q

Advantages of using MHT in early menopause?

A
  • ↓ risk of heart disease
  • Longer lifespan
  • May prevent Alzheimer’s disease in later life
  • May improve depressive/anxiety symptoms but antidepressants 1st line
81
Q

Summary: benefits and risks

A
  • In women requiring combined MHT, the use of a neutral progestogen such as micronised progesterone or dydrogesterone may be associated with lower risks of breast cancer and VTE
  • Each women’s individual risks and needs should be assessed before initiating therapy
  • Initiation of menopausal hormone therapy (MHT) a safe option for healthy, symptomatic women who are within 10 years of menopause or younger than age 60 years and who do not have contraindications to MHT

CI include

  • Breast cancer n
  • Cerebrovascular disease (stroke) or coronary artery disease n
  • History of thromboembolic disease (VTE) n
  • Active liver disease n
  • Unexplained vaginal bleeding

> Estrogen-progestin therapy – intact uterus

> Unopposed estrogen - post-hysterectomy

> Vaginal atrophy symptoms only - vaginal estrogen

Bal (CPT) (27 decks)

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