Management of the menopause and climacteric.
Adesina Olubukola Dept of OBGYN, UCH, Ibadan.
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.
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.
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.
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
Premature ovarian failure (resistant ovary syndrome) Surgical menopause. Therapeutically. Mgt of malig disease in young women.
Begin long before cessation of menstruation. Triggered b relative fall in circulating OEST. Physical
– Tiredness, insomnia, vasomotor, vaginal dryness,
– 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
EST is absorbed from stomach and duodenum, passed up the portal system and through the liver.
– Converted in liver into oestrone. Results in
Hormone replacement therapy(2) oral
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
• 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)
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 neurodegenerative disease.
LOCAL OESTROGENS SELECTIVE OESTROGEN RECEPTOR MODULATORS (SERM)