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7006PHM Prof Pharm II > Menopause + MHT > Flashcards

Menopause + MHT Flashcards

1
Q

What happens to the hormones in menopause?

A

Dec in oestrogen secretion by ovarian follicular unit –> inc gonadotrophins (LH and FSH from anterior pituitary

Remaining follicles are insensitive to FSH and LH

Perimenopause = beginning of missed cycles

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2
Q

What is perimenopause?

A

Transition before menopause (last 5 yrs)

physical and emotional changes, periods become irregular (heavy, long, or irregular)

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3
Q

What is menopause?

A

Permanent cessation of menstruation = all ovarian follicles depleted and ovarian oestrogen production ceases

Clinical = absence of menses for at least 12 consecutive months

Factors influencing symptoms = genetic predisposition, ovarian cystectomies

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4
Q

What does drug therapy for menopause aim to do? (general)

A

Treat:
- vasomotor symptoms
- vaginal dryness
- dyspareunia

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5
Q

Discuss menopausal vasomotor instability symptoms

A

Hot flush (75-85%) = directly proportional to drop in oestrogen - red face/neck, inc skin temp, inc heart rate

Nausea, dizziness, headache, palpitation

Formication

Common in last 12-24 of menstrual period

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6
Q

How is menopausal vasomotor instability treated?

A

W/ menopausal hormonal therapy (MHT)

Systemic estrogen –> best treatment for hot flushes
Intravaginal oestrogen –> less effective for hot flushes

Alternatively = clonidine –> menopausal flushing, use limited by ADRs

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7
Q

What is used to treat menopausal vasomotor instability if MHT is C/I?

A

Antidepressants, gabapentin = limited evidence that short term low dose treatment does anything to reduce hot flushes

Low dose SSRIs or SNRIs = short trials showed reduction in number/severity of hot flushes —> venlafaxine and paroxetine more effective

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8
Q

Discuss vaginal atrophy due to menopause

A

Oestrogen receptors in vagina, vulva, urethra –> des oestrogen –> atrophy of tissue

Physiological changes:
- dec subcutaneous fat and elasticity
- paleness and thinning of vaginal epithelium –> reduced secretion, distensibility

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9
Q

What are the symptoms of menopause vaginal atrophy?

A

Vaginal dryness

Pruritus, tears or bleeding, painful urination

painful sexual intercourse

Alkalinisation of vaginal pH –> more infections

Worsen with age

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10
Q

What are the treatments for vaginal atrophy due to menopause?

A

Systemic MHT = for those w/ systemic symptoms

Intravaginal oestrogen

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11
Q

Discuss menopausal urethral syndrome and its symptoms

A

Oestrogen receptors in trigone of bladder –> tissue atrophy and loss of pelvic tone

Symptoms = stress incontinence, urge incontinence

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12
Q

How is menopausal urethral syndrome treated?

A

Pelvic floor exercises
Systemic MHT
Intravaginal oestrogen

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13
Q

What are the risk factors to osteoporosis?

A

Slender, sedentary females
Caucasian or Asian descent
Smoking/alcohol use
Low intake of calcium and vitamin D
family history
Chronic steroid use

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14
Q

What is the treatment for CHD in menopausal women (pharm and lifestyle)?

A

Diet, exercise, +/- pharm drug therapy (lipid lowering agents)

Control of complications = diabetes, HTN, hypercholesterolaemia

Smoking cessation, moderation in alcohol consumption, stress reduction

Oestrogen replacement therapy (ERT) = inc HDL, dec LDL (transdermal oestrogen no effect here)

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15
Q

What effect would combined MHT have on menopausal CHD risk?

A

May attenuate or eliminate benefit on HDL cholesterol

Therapy limited to low doses, reserved for those w/ intact uterus

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16
Q

What tests should be conduction prior to menopausal treatment?

A

Full gynaecological hx and examination (breast, cervical, pelvis)

Mammography (>50 years of age)

blood pressure, blood lipids

complete blood examination

Thyroid stimulating hormone

bone density

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17
Q

What are some cancer risks with menopausal hormone therapy (MHT)?

A

Incidence of breast cancer inc w/ age

- Oral/transdermal inc breast cancer risk --> associated w/ duration of use, lower risk w/ cyclical treatment
- Low dose vaginal oestrogen does not inc risk of breast cancer

Endometrial cancer (oestrogen only MHT)
- reduce risk w/ progestogen at least 10 days/month

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18
Q

What are additional risks associated w/ menopause hormone therapy?

A

Both oestrogen + combined therapy = Coronary heart disease (combined mostly), VTE (combined therapy), Stroke

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19
Q

What are C/I to systemic menopausal hormone therapy?

A

Aged >60 yrs

Previous or active thromboembolic disorder

Unexplained uterine bleeding

Severe liver disease

uncontrolled HTN

Breast cancer or other oestrogen dependent tumour

Cerebrovascular or coronary artery disease

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20
Q

What is the role of oestrogen in MHT?

A

Relieves reduced oestrogen symptoms

Estriol, estradiol, conjugated equine estrogens

21
Q

What is the role tibolone in MHT?

A

Relief menopause symptoms + prevent post-menopausal osteoporosis (in high fract risk + Tx inappropriate)

- Oestrogenic on vagina, bone, thermoreg
- Progestogenic/anti-estrogen on breast/endometrium 
- Androgenic effects = dec HDL, TG, Lipoprotein A
22
Q

What is the role of progestogens in MHT?

A

Supportive role = uterine protection (dec unopposed oestrogen cancer), contraceptive cover, suppression of menstrual cycle

Medroxyprogesterone, norethisterone, dydrogesterone

23
Q

Discuss the benefits of oral routes of MHT administration

A

Inexpensive, convenient, well tolerated

risk ADRs

24
Q

Discuss the benefits of transdermal routes of MHT administration

A

Avoid first pass effect allows smaller doses –> reduce ADRs

Risk of VTE or stroke lower, can cause skin irritation

25
Q

Discuss generally vaginal preparation routes of MHT

A

First choice for urogenital symptoms, few ADRs

Recommended that treatment is stopped at least annually

Progestogen not necessary for endometrial protection

Irregular/atypical bleeding may indicate endometrial pathology

26
Q

Discuss the use of estrogen only MHT

A

Recommended post-hysterectomy w/ no endometriosis hx (endo can still cause hyperplasia/endo cancer)

estrogen is continious

27
Q

What is conjugated equine estrogens?

A

Oestrogen derived from a pregnant mare’s urine

28
Q

Discuss the use of intravaginal oestrogen

A

local oestrogen therapy for predominantly genitourinary symptoms (dysuria, urinary freq, vaginal atrophy)

also for those where systemic treatment C/I

Need a 12 day course of progestin every 6-12 months –> reduce cancer risk

29
Q

What risks should be considered with intravaginal oestrogen?

A

Some systemic absorption can occur, safety can’t be guaranteed

Estradiol has more sig effect on serum estrogen concentration than estriol

women w/ vaginal dryness w/ hx of breast cancer should try non-hormonal preparations first

30
Q

When should combined MHT be used?

A

Women with intact uterus, contains both progestogen and estrogen

May be cyclical or continues and prevents risk of endometrial hyperplasia

Considered if hx of endo

31
Q

Discuss the use of progestogens in MHT

A

May be combined or dosed separately

reduces endometrial cancer risk associated w/ unopposed oestrogen

Micronised progesterone
Norethisterone
medroxyprogesterone
dydrogesterone (only in combination)

32
Q

Discuss the use (guidelines, process) for combined cyclical MHT regimen

A

Indicated for perimenopausal or early postmenopausal women, use until 12-18 months after last menses

Cont. oestrogen, plus progestogen for at least 10-14 days/month or 14 days/3months

W/drawal bleed after progestogen stops

33
Q

What is an alternative to combined cyclical MHT regimens for <50 years?

A

low dose COC

Symptoms may occur during pill free week

34
Q

Discussed continuous combined MHT regimens

A

Continuous oestrogen plus continuous progestogen = half or quarter of cyclic dose

Stimulate endometrium less (less hyperplasia) than sequential/unopposed oestrogen

No scheduled bleed = 50% bleed irregularly in first 6 months, 90% amenorrhoeic after 12 months

35
Q

What is typically in continuous combined MHT? (active ingredient)

A

Estradiol 1 mg +:

Dydrogesterone, norethisterone

36
Q

What are the C/I for tibolone use in MHT?

A

Breast cancer, hormone-dependent cancer

SLE, coronary artery disease

cerebrovascular disease

VTE, severe liver disease

Avoid use in >70yrs of age

avoid in inc stroke risk = HTN, diabetes, smoking, AF

37
Q

What are the estrogen related ADRs of MHT?

A

Breast enlargement/tenderness
Fluid retention
Headache
Leg cramps
Nausea

38
Q

How are estrogen related ADRs of MHT managed?

A

Reduce dose
changing the oestrogen
change the route
taking w/ food or at night = reduce nausea

39
Q

What are the progestogen related ADRs of MHT?

A

Breast enlargement/tenderness
Fluid retention
Headache
depression
PMS-like syndrome
Acne

40
Q

How are progestogen related ADRs of MHT managed?

A

Changing the progestogen

Reduce dose (Ensure endometrium protected)

changing the route

reduce duration of progestogen to 10days/month

Changing to a 3monthly cyclical regimen

Changing to continuous combined MHT if postmenopausal

41
Q

List alternative menopausal drugs/regimens

A

SERMs
Raloxifene
Testosterone cream

42
Q

Discuss the use of Raloxifene in menopause treatment

A

Estrogen agonist - bone (inc BMD, dec vert fractures), lipoprotein metabolism

Estrogen antagonist - uterine and breast tissue

Used in postmenopausal osteoporosis and prevention of breast cancer in high risk postmenopausal women

43
Q

What is raloxifene unable to do?

A

Not stimulate endometrium

No effect on vasomotor symptoms

44
Q

Discuss the use of SERM in menopause management

A

Indicated for moderate to severe vasomotor symptoms in women w/ intact uterus

Bazedoxifene = inhibit stim effects of oestrogen on endometrium, reduce risk of endometrial cancer

Reserved for women who cannot take estrogen/progestogen combinations

45
Q

What is SERM?

A

Conjugated oestrogen/bazedoxifene

46
Q

Discuss the use of testosterone cream in menopause treatment/management?

A

Used as adjunct to MHT, direct androgenic effect = takes 4-8 wks for benefit

Indication = postmenopausal women w/ low libido w/ associated distress (hypoactive sexual desire dysfunction)

ADRs = acne, inc body hair, weight gain

47
Q

Outline some practice points for MHT

A

no difference in recurrence of vasomotor symptoms between gradual and abrupt MHT w/drawal

No benefit to reduction in risk of CVD

No contraceptive protection, does not treat chronic illness

oestrogen dose used in MHT 5-6 times less than that of COCs

48
Q

What are the alternative treatments for vaginal atrophy?

A

Moisturisers = moisturise vagina (replens, aci-jels, vagisil)

Vaginal acidifiers = aci-jel (glacial acetic acid, hydroxyquinoline, ricinoleic acid), multi- gyn active gel (lowers pH, from plant extract), vagicare (ascorbic acid pessaries)

49
Q

List some CAMs for menopause

A

Black cohosh

Phyto-estrogens

Dong quai

Wild yam, natural progesterone cream

Bio-identical hormone therapies

no evidence for many of these

7006PHM Prof Pharm II (24 decks)

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