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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
Discuss generally vaginal preparation routes of MHT
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
Discuss the use of estrogen only MHT
Recommended post-hysterectomy w/ no endometriosis hx (endo can still cause hyperplasia/endo cancer) estrogen is continious
27
What is conjugated equine estrogens?
Oestrogen derived from a pregnant mare's urine
28
Discuss the use of intravaginal oestrogen
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
What risks should be considered with intravaginal oestrogen?
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
When should combined MHT be used?
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
Discuss the use of progestogens in MHT
May be combined or dosed separately reduces endometrial cancer risk associated w/ unopposed oestrogen Micronised progesterone Norethisterone medroxyprogesterone dydrogesterone (only in combination)
32
Discuss the use (guidelines, process) for combined cyclical MHT regimen
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
What is an alternative to combined cyclical MHT regimens for <50 years?
low dose COC Symptoms may occur during pill free week
34
Discussed continuous combined MHT regimens
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
What is typically in continuous combined MHT? (active ingredient)
Estradiol 1 mg +: Dydrogesterone, norethisterone
36
What are the C/I for tibolone use in MHT?
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
What are the estrogen related ADRs of MHT?
Breast enlargement/tenderness Fluid retention Headache Leg cramps Nausea
38
How are estrogen related ADRs of MHT managed?
Reduce dose changing the oestrogen change the route taking w/ food or at night = reduce nausea
39
What are the progestogen related ADRs of MHT?
Breast enlargement/tenderness Fluid retention Headache depression PMS-like syndrome Acne
40
How are progestogen related ADRs of MHT managed?
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
List alternative menopausal drugs/regimens
SERMs Raloxifene Testosterone cream
42
Discuss the use of Raloxifene in menopause treatment
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
What is raloxifene unable to do?
Not stimulate endometrium No effect on vasomotor symptoms
44
Discuss the use of SERM in menopause management
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
What is SERM?
Conjugated oestrogen/bazedoxifene
46
Discuss the use of testosterone cream in menopause treatment/management?
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
Outline some practice points for MHT
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
What are the alternative treatments for vaginal atrophy?
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
List some CAMs for menopause
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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