1. Menopausal Symptoms & Management
PHARMACY PROFESSIONAL REVIEW COURSE
SPRING
Ph. Anand Davidson.

2. Definition:
Menopause is defined as the permanent cessation of menstruation resulting from loss of ovarian follicular activity.
The phase in the aging process of women marking the transition from the reproductive stage of life to the non-reproductive stage
It is signalled by the last menstrual period
The average age of menopause is 51.

3. Two Phases:
1. Perimenopausal Phase Women will experience erratic periods before the final cessation due to inadequate ovarian oestrogen secretion and this transitional phase lasts around 4-5 years 2. Postmenopausal Phase The occurrence of the last menstruation usually taken as being final if it is followed by a 12-month blood-free interval.

4. Menopause - Types Premature menopause – before 40 years
Surgical menopause – hysterectomy, oophorectomy
Natural menopause – mean age 51 years
Late Menopause – after 55 years
DIAGNOSIS:
High FSH level ( >30iu/L)
Low estradiol level ( <100pmol/L)
The problems associated with the menopause result from oestrogen deprivation

5. Vasomotor symptoms: hot flushes, night sweats and palpitations
Menopausal symptoms
Vasomotor symptoms: hot flushes, night sweats and palpitations
Urogenital atrophy: vaginal dryness, dyspareunia, pruritus vulvae, urinary frequency, urgency, and recurrent cystitis
Psychological symptoms: irritability, nervousness, depression, insomnia , anxiety and decreased libido
Osteoporosis: loss of calcium from the bones, frequent fractures
Coronary heart disease: change in blood lipid profile

6. Management of menopause
Advise on a healthy life style
Psychological support
Hormone replacement therapy
Venlafaxine, Clonidine
Tibolone, Raloxifene and the bisphosphonates

7. Management of menopausal symptoms
Understand menopause
Strengthening of self-image
Avoid spicy food, alcohol, strong tea and coffee.
Healthy life style
Hormone Replacement Therapy

8. Prevention of osteoporosis
Change lifestyle risk factors
Exercise
Adequate calcium / vitamin D intake
Hormone Replacement Therapy
Tibolone
Alendronate
Raloxifene

9. Possible mechanism of Cardioprotection by HRT
Favourable lipid profile:  HDL,  LDL,  Lipoprotein (a)
Other effects:  insulin sensitivity, vascular dilatation,  coagulation factors

10. Indications for HRT Relief of menopausal symptoms
Long term prevention of osteoporosis

11. Absolute contraindications
Undiagnosed postmenopausal vaginal bleeding
Oestrogen dependent tumour
Venous thrombo-embolism / stroke
Acute liver disease

12. Routes of administration for oestrogens in HRT.
Oral
Transdermal (patches/gels/cream)
Intranasal
Subcutaneous (Implants)
Vaginal (creams and medicated rings)

13. Oral therapy
Natural occurring oestrogens: includes conjugated estrogen and various oestradiol preparations. These oestrogens are metabolised in the liver to the weaker metabolite oestrone and then converted to oestradiol in the peripheral circulation and in the target tissue.
Tibolone: a steroid hormone that has oestrogenic, progestogenic and androgenic properties.
Synthetic oestrogens: such as mestranol or ethinyl oestrodiol are not generally prescribed for older women for HRT.

14. Transdermal therapy
Patches (oestrogen only or combined preparation) or oestrogen gels
Women’s preference
Skin irritation may be a problem but new matrix patches and the gels are usually well tolerated
Route of choice for women with risk factors for venous thrombo-embolism, liver disease or gastro-intestinal problems

15. Treatment of Menopausal symptoms with Estrogen
Gold standard for relief of menopausal symptoms
Contraindications-breast cancer, CHD, venous thromboembolism/stroke
Duration- 6 months to 5 years
Dose- low-dose is recommended
Conjugated estrogens 0.3mg or Estradiol 0.5mg
Adding a Progestin-to prevent endometrial hyperplasia and cancer with unapposed estrogen therapy (medroxyprogesterone 1.5mg daily)

16. Treatment of Menopausal symptoms with Estrogen
Low-dose oral contraceptives- low estrogen oral contraceptive-20mcg of ethinyl estradiol to treat perimenopausal symptoms

17. Treatment of vasomotor instability in women not taking estrogen
Venlafaxine 75mg daily – reduces hot flushes by 61%
Side effects- Dry mouth, anorexia, nausea, constipation
Clonidine Hcl- 50mcg to 75mcg twice daily

18. Treatment of Urogenital changes
Sexual function – systemic or vaginal estrogen therapy to treat decreased vaginal lubrication, decreased sexual function and Dyspareunia
Urinary incontinence - systemic or vaginal estrogen
Urinary tract infections – suitable antibiotics

19. Treatment of urogenital atrophy in women not taking systemic estrogen
Vaginal moisturizers and lubricants – Astroglide
Low-dose vaginal estrogen – concomitant progestin theapy is not necessary
Vaginal ring estradiol-delivers 6 to 9 mcg / day for a period of 3 months
Conjugated estrogens vaginal cream-0.5g of cream / 1/8th of the applicator full daily for 3 weeks followed by twice weekly

20. Treatment of urogenital atrophy in women not taking systemic estrogen
Estradiol vaginal cream- cream-0.5g (50mcg of estradiol)of cream / 1/8th of the applicator full daily for 3 weeks followed by twice weekly
Estradiol vaginal tablet- each vaginal tablet contains 25mcg of estradiol – twice/week

21. Nonpharmacologic therapy of Osteoporosis
Diet- rich in calcium and vitamin D
Calcium- daily 1000 to 1500mg of elemental calcium in divided doses with meals
Vitamin D to 800 IU daily
Exercise- at least 20 minutes of weight bearing exercises daily to reduce rate of bone loss
Cessation of smoking to reduce bone loss

22. HRT regimens
Women who have had a hysterectomy only need to take oestrogen
Women with an intact uterus must take progestogen for endometrial protection to prevent endometrial cancer or hyperplasia
Regular surveillance of endometrium is required for women (extreme intolerance of progestogen) on unopposed oestrogen

23. HRT regimens
Sequential preparation: progestogen added for days each month. Some women will not bleed on sequential preparations and this is not a cause for concern provided that the progestogen is taken correctly.
Continuous combined HRT: give oestrogen and progestogen daily. These preparation induces endometrial atrophy. Intermittent bleeding and spotting are common in the first few month of use. More suitable for women who are at least one year since their last spontaneous period.

24. Progestogen Oral or transdermal form
Levo-norgestrel releasing intra-uterine system

25. Oral progestogens
C21 progesterone derivatives : dydrogesterone or medroxyprogesterone acetate
C19 nor-testosterone derivatives: norethisterone acetate or levonorgestrel

26. Side effects of HRT Nausea breast pain
heavy or painful withdrawal period
premenstrual syndrome type of side effects
weight gain

27. Risk of HRT
Breast cancer
Thrombo-embolism

28. HRT and venous thrombo-embolism
Natural oestrogens
Women taking HRT have a 2-4 fold increase in risk of venous thrombo-embolism (VTE).
Overall risk remain small: 1 in 5000 and mortality from VTE is around 1-2%.
Women with significant past history of VTE should have a thrombophilia screen before commencing HRT

29. Menopausal symptoms
Duration of treatment will depend upon the women’s preference and the presence of risk factors
In the absence of risk factors, HRT can be stopped after 2 years

30. Monitoring of women on HRT
Compliance of treatment, symptoms control, side effects and bleeding pattern
Cervical smear

31. Other options for management of menopausal symptoms and prevention of osteoporosis
Tibolone:
Steriod hormone
The parent compound and its metabolites can all bind to steroid receptos
Oestrogenic, progestogenic and androgenic properties
Different hormonal effects predominate in different tissues.
Oestrogenic: climacteric symptoms, bone and lipid
Progestogenic: endometrium
Androgenic: libido
Breast: less breast pain and no change in breast density on mammography

32. Other options for prevention of osteoporosis
Bisphosphates:
Etidronate and Alendronate
Inhibitors of bone turnover and slow down or prevent bone loss
Both need to be taken on an empty stomach
Non-hormonal agents
Treatment of choice for older women and those with contra-indications to HRT

33. Prevention and treatment of Osteoporosis- Other Options
Screening of Osteoporosis – Measurement of BMD
Bisphosphonates- adsorbed on to hydroxyapatite crystals in bone, slowing both their rate of growth and dissolution, and therefore reducing the rate of bone turnover.
Alendronate sodium
Treatment-10mg / day or 70mg once a week
Prevention- 5mg / day or 35mg / week
Risedronate sodium
Prevention and treatment- 5mg / day or 35 once per week

34. Bisphosphonates
Alendronate or risedronate should be taken with a full glass of water 30 minutes before the first meal or beverage of the day.
Patients should not lie down for atleast 30 minutes after taking the dose to avoid the unusual complication of pill-induced esophagitis
Disodium etidronate 200mg daily for 14 days
Avoid food, calcium containing products, iron and mineral supplements, antacids for atleast 2 hours before and after oral treatment.

35. Prevention and treatment of Osteoporosis- Other Options
Raloxifene- a selective estrogen receptor modulator
Prevention and treatment of osteoporosis – 60mg/day
Strontium Ranelate- treatment of post menopausal osteoporosis to reduce risk of vertebral and hip fractures- 2g once daily in water, preferably at bed time
Avoid food, calcium containing products, iron and mineral supplements, antacids for atleast 2 hours before and after oral treatment.
Tibolone- Osteoporosis prophylaxis- 2.5mg daily

36. Selective oestrogen receptor modulators (SERMs)
Raloxifene
Selective oestrogen receptor modulators (SERMs)
Agonist and antagonist properties
Bone protective and reduce cholesterol
No effect on the endometrium
Evidence to suggest that it is protective against breast cancer
Does not help menopausal symptoms and may worsen them