Menopause + MHT Flashcards
What happens to the hormones in menopause?
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
What is perimenopause?
Transition before menopause (last 5 yrs)
physical and emotional changes, periods become irregular (heavy, long, or irregular)
What is menopause?
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
What does drug therapy for menopause aim to do? (general)
Treat:
- vasomotor symptoms
- vaginal dryness
- dyspareunia
Discuss menopausal vasomotor instability symptoms
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
How is menopausal vasomotor instability treated?
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
What is used to treat menopausal vasomotor instability if MHT is C/I?
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
Discuss vaginal atrophy due to menopause
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
What are the symptoms of menopause vaginal atrophy?
Vaginal dryness
Pruritus, tears or bleeding, painful urination
painful sexual intercourse
Alkalinisation of vaginal pH –> more infections
Worsen with age
What are the treatments for vaginal atrophy due to menopause?
Systemic MHT = for those w/ systemic symptoms
Intravaginal oestrogen
Discuss menopausal urethral syndrome and its symptoms
Oestrogen receptors in trigone of bladder –> tissue atrophy and loss of pelvic tone
Symptoms = stress incontinence, urge incontinence
How is menopausal urethral syndrome treated?
Pelvic floor exercises
Systemic MHT
Intravaginal oestrogen
What are the risk factors to osteoporosis?
Slender, sedentary females
Caucasian or Asian descent
Smoking/alcohol use
Low intake of calcium and vitamin D
family history
Chronic steroid use
What is the treatment for CHD in menopausal women (pharm and lifestyle)?
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)
What effect would combined MHT have on menopausal CHD risk?
May attenuate or eliminate benefit on HDL cholesterol
Therapy limited to low doses, reserved for those w/ intact uterus
What tests should be conduction prior to menopausal treatment?
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
What are some cancer risks with menopausal hormone therapy (MHT)?
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
What are additional risks associated w/ menopause hormone therapy?
Both oestrogen + combined therapy = Coronary heart disease (combined mostly), VTE (combined therapy), Stroke
What are C/I to systemic menopausal hormone therapy?
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
What is the role of oestrogen in MHT?
Relieves reduced oestrogen symptoms
Estriol, estradiol, conjugated equine estrogens
What is the role tibolone in MHT?
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
What is the role of progestogens in MHT?
Supportive role = uterine protection (dec unopposed oestrogen cancer), contraceptive cover, suppression of menstrual cycle
Medroxyprogesterone, norethisterone, dydrogesterone
Discuss the benefits of oral routes of MHT administration
Inexpensive, convenient, well tolerated
risk ADRs
Discuss the benefits of transdermal routes of MHT administration
Avoid first pass effect allows smaller doses –> reduce ADRs
Risk of VTE or stroke lower, can cause skin irritation
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
Discuss the use of estrogen only MHT
Recommended post-hysterectomy w/ no endometriosis hx (endo can still cause hyperplasia/endo cancer)
estrogen is continious
What is conjugated equine estrogens?
Oestrogen derived from a pregnant mare’s urine
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
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
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
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)
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
What is an alternative to combined cyclical MHT regimens for <50 years?
low dose COC
Symptoms may occur during pill free week
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
What is typically in continuous combined MHT? (active ingredient)
Estradiol 1 mg +:
Dydrogesterone, norethisterone
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
What are the estrogen related ADRs of MHT?
Breast enlargement/tenderness
Fluid retention
Headache
Leg cramps
Nausea
How are estrogen related ADRs of MHT managed?
Reduce dose
changing the oestrogen
change the route
taking w/ food or at night = reduce nausea
What are the progestogen related ADRs of MHT?
Breast enlargement/tenderness
Fluid retention
Headache
depression
PMS-like syndrome
Acne
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
List alternative menopausal drugs/regimens
SERMs
Raloxifene
Testosterone cream
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
What is raloxifene unable to do?
Not stimulate endometrium
No effect on vasomotor symptoms
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
What is SERM?
Conjugated oestrogen/bazedoxifene
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
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
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)
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
