Management of the

menopause and
climacteric.
Adesina Olubukola
Dept of OBGYN,
UCH,
Ibadan.
 Menopause
 Ancient Greek words: menos (month) and pausos
(ending)- end of monthly /menstrual cycle, the
central ext marker of human female fertility.
 After 1 yr of amenorrhoea in a women age 45yrs
or over. Modal age- 51 yrs.
 An event in whole range of anatomical,
physiological and psychological events which
contribute to the climacteric.
 Climacteric
 Klimakter (Greek)- rung of ladder. Major
movement on life’s ladder.
 Transition from fertility to infertility. 45-55yrs
when woman passes from reproductive into her
post-reproductive years.
 Wide variety of sympts, signs, mtblc adjustment.
 Ultimate cause of which is a major reduction in
level of circulating ESTG.
 Pathophysiology (1)
 Human ovary basically consists of outer cortex
(containing follicles) and a central medulla.
Cortex and medulla contain stroma which are
supportive in function and actively involved in
steroid synthesis.
 The dvlpg follicle produces the bulk of OEST
circulating in plasma of pre-menopausal woman.
Median lvl btw 400-500pmol/l.
 Syth principally from androgens to OEST in
granulosa cells. Aromatase enz promoted by
FSH.
 Pathophysiology (2)
 Theca cells produce OEST from androgens
stimulated by LH.
 1st sign of approaching menop is decline in
fertility in 4th decade.
 1st endocrine change- fall in inhibin production
by ovary, glycoprot that inhibits production of
FSH . Plasma FSH lvl rise above 5iu/l. later LH
rise above premenopausal limit of 12iu/l
 Other causes
 Premature ovarian failure (resistant ovary
syndrome)
 Surgical menopause.
 Therapeutically.
 Mgt of malig disease in young women.
 Symptoms (1)
 Begin long before cessation of menstruation.
Triggered b relative fall in circulating OEST.
 Physical
– Tiredness, insomnia, vasomotor, vaginal dryness,
urinary symptoms.
 Psychological
– Mood swings, anxiety, loss of short-term memory,
lack of concentration, loss of self-confidence,
depression.
 Symptoms (2)- vasomotor
 Hot flushes, night sweats. 70% periM.
 Freq(few to several dozens per day). Duration
(few wks to many years).
 Vascular response to a central disturbance of
thermoregulatory center in the hypothalamus.
 If episode at night, pt experiences repeated
awakening, loss of sleep quality/quantity, xnic
incursion into deep sleep- REM sleep- deep sleep
rhythm.
Symptoms (3)- vaginal dryness
 Can lead to disharmony
 Vagl skin dependent on EST for depth,
lubrication (becs thin and poorly
moisturized)
 Symptoms (4)-
psychological sympts
 Equally distressing and disabling.
 ?due EST def ?due sleep deprivation. periM yrs
marked by life events. Intrinsic personality type
(tendency to anxiety, neurosis, low self-esteem).
 No true increase in formal psychiatric disorders
a.

 NB- severity, duration and nature of menoP

sympt are highly variable.
 Symptoms (5)-
urinary sympts
 MenoP women freq c/o suggestive of UTI.
Negative urine culture.
 EST receptor in the trigone and proxl
urethra.
 Stress incont freq. In absence of uterovagl
prolapse attributable to EST def.
 Symptoms (6a)-
skeletal sympts
 2 types of bones- compact and trabecular.
– Compact- 80%, insensitive to EST.
– Trabecular- 20%, highly sensitive: vtbr, distal
radius, femoral neck, calcaneus.
 EST is physiological restraint on bone
turnover. Holds balance btw bone
resorption and bone formation.
 Symptoms (6b)-
skeletal sympts
 After menoP decoupling xterised by greater bone
resorption than formation .
 Trabecular bone with high surface area is
particularly at risk.
– Trabecular bone is shock-absorbing bone, due vast
network of interconnecting trabecular. when this
network degraded by prog loss of trabecular number,
thickness and interconnection, the bone become liable
to fracture after minimal moderate trauma.
• Traumatic fracture affects distal radius and femoral neck
while non-traumatic fracture affect the vtrbr.
 Symptoms (7)-
cardiovascular sympts
 Incid of events such as myocard infarction is
lower in premenopausal women than men of
same age.
 Decline in plasma EST attended by changes in
lipid profile that is conducive to atherogenesis
– Incr total cholest/LDL cholest, red HDL cholest.
 EST exerts direct effects on vessel wall.
– Stimulates nitrogen synthase to produce nitric oxide.
 Loss of EST results in promotion of both
atherogenesis and vasoconstriction.
 Hormone replacement
therapy(1)
 Elicits strong opposing views
Consultation
 Full history-
– presence/impact of sympts (personal, domestic,
sexual)
– Family hx- cardiovascular(angina, myocard infarction
etc), skltl dx(osteoporosis), Alzheimer’s
– GIT/ liver disease- interfere with pharmacodynamics
of EST.
– Gynae hx-all prev med/surg intervention. Condition
infl by plasma EST. Benign/malig breast dx.
 Examination- Identify potentially EST sensitive tumours in
 Hormone replacement
therapy(2)
oral
 EST is absorbed from stomach and duodenum,
passed up the portal system and through the liver.
– Converted in liver into oestrone. Results in
OEST:oestrone ratio of 1:2.
• Can be taken any time, cheap, convenient, well tolerated
 Activation of certain hepatic enzs. Some effect on
hepatic release of prot of coagulation cascade

– (incr in risk of VTE from 1.5-3.5 per 10,000 per year).

• Given dialy. Oestradiol valerate 1mg or 2mg. Conjugated
equine estrogen 0.625mg or 1.25mg. Oestrone1.25mg
 HRT(3)- transdermal oestrogen
 Attempts to mimic physiology of the
premenopause.
– Reservoir/ matrix patches.
 EST is lipid soluble, passes directly into the
systemic circulation. OEST:oestrone ratio of 2:1.
– 50ug patch/0.625mgconjugated equine EST/2mg oral
OEST
• Percutaneous gel- variant of transdermal patch
 Absorption produces therapeutic plasma levels
within 4 days of commencement and Rx is well
tolerated.
 HRT(4)- subcutaneous implant
 Restricted to pts who have undergone
hysterectomy (+/- oophorectomy). Pellet of
OEST in subcut tissue of the lower
abdomen .
 Review at 6/12 intervals. Very well
tolerated. Tachyphylaxis.
 Annual checks on plasma OEST be4
reimplantation (<1000pmol/l)
 HRT(5)- progestogens
 EST alone- signif endomet hyperpl, neoplasia.
– 12 days monthly(secretory transf of endometrium and
satisfactory shedding). Not necessary post hysterectomy

• May cause adverse effect (esp 19 nor group) eg blotting,

• To avoid cyclic effects give cont comb approach- suppresses
EST receptor production in endometrium preventing
proliferation and rendering pt free of cyclic bleeding.
• Fears the PROG may annul cardio-protective effects of EST
unfounded

• C-21- derived form native progesterone. C-19- derived from

testosterone
 HRT (6)- gonadomimetic
therapy
 Only licensed product- Tibolone
 Synthetic steroid with estrogenic , progestogenic
and androgenic activity
 2.5 mg daily to women at least 1 year after
menoP.
 Suppresses symptoms and prevents bone loss.
 Mild androgenic side effect but generally well
tolerated.
 HRT (8)- contraindications
Absolute
 Pregnancy
 Suspicion of breast cancer
 Suspicion of endomet
cancer
 Acute /active liver
disease
 Uncontrolled HTN.
 confirmed venous TE
Relative
 Uterine fibromyomata
 Past hx of benign breast
dx
 Unconfirmed VTE
 Xnic stable liver dx
 migraine
 HRT (9)- mgt of pt receiving
HT
 1st 12 wks critical- counsel on startup
sympts
 Severity related to interval since menop.
Usually temporary.
 1st review(3/12)- enquire about resolution
of menop sympts and startup effects. Next
review 6/12
 Annual review- breast, BP, pelvic exam
HRT (10a)- central nervous syst
 HRT favorably impacts psychological sympts of
EST def.
– Prompted studies into role in preventing/Rx of
Alzheimer's dx/ related neuro-degenerative disorders.

Physiological basis
• EST enhances central blood flow
• Acts as mono-amine oxidase inhibitor
• EST receptors in key areas of CNS e.g. hippocampus
(interface btw short and long term memory)
HRT (10b)- central nervous syst
 Cognitive fxn shown to improve in symptomatic
but not asympt perimenoP women.
– Meta-analysis addressing incid of dementia conclude
the prior use of EST assoc with decr incid of 1/3.

• True relationship bet HRT exposure and subseq Alzheimer's

dx and related dementia now requires testing
• Use of HRT in Alzheimer’s not indicated
• At present HRT not licensed for prevention of neuro-
degenerative disease.
 LOCAL OESTROGENS
 SELECTIVE OESTROGEN RECEPTOR
MODULATORS (SERM)