1. Sharan Pobbathi Alena Billingsley
Menopause and HRT
Sharan Pobbathi
Alena Billingsley

2. Will cover: What is the menopause? Diagnosing the menopause Management
Non-hormonal
HRT
Premature menopause

3. Programme Patient experience Presentation Case Studies (CSA style)
Quiz

4. Menopause – what and when
The menopause may be
Natural or induced
Natural menopause is the permanent cessation of the menstrual cycle due to loss of ovarian follicular activity
Only known retrospectively one year after the last period
Average is 51 years

5. Induced menopause Specific treatment e.g. chemotherapy or radiotherapy
Oophorectomy
Treatment with gonadotrophin-releasing hormone (GnRH) analogues

6. Diagnosis - symptoms Short Term Musculoskeletal Vasomotor
Flushes
Night sweats
Insomnia
Sexual dysfunction
Vaginal dryness
Dyspareunia
Decreased libido
Musculoskeletal
Joint aches
Fat redistribution
Psychological
Depressed mood
Anxiety
Irritability
Mood swings
Lethargy
Difficulty concentrating

7. Consequences of the menopause
Long term
Osteoporosis
1 in 3 increase in risk of fracture
Cardiovascular disease
MI and stroke most common cause of death >60y
Oophoretomised women have 2-3 fold risk of CHD
Urogenital
Lower urinary tract and pelvic floor atrophy leading to frequency, urgency, nocturia, incontinence, recurrent infections
Vaginal atrophy

8. Investigations FSH is only used if diagnosis is in doubt
FSH >30 iu/L
Don’t do LH, oestradiol and progesterone as not helpful
TFTs if confusion about symptoms
BMD if significant risk of osteoporosis

9. Management – Non-hormonal
Lifestyle advice
Avoid hot drinks especially caffeinated ones, and alcohol
Stop smoking
Fans and layering
Use of vaginal moisturisers e.g. Replens MD® and Sylk ®
No evidence that diet (phytoestrogens) affects symptoms

10. Management – Non-hormonal
OTC remedies
Black cohosh
Oestrogen like effect
May help with emotional symptoms
Interacts with antihypertensives and risk of liver failure
St John’s Wort
Recognised anti-depressant effects
Lots of interactions

11. Management – Non-hormonal
Licensed
Clonidine for hot flushes
SEs insomnia, dry mouth, dizziness, constipation, drowsiness
Unlicensed
SSRIs/SNRI (venlafaxine) for mood swings, vasomotor symptoms
Gabapentin for musculoskeletal; SEs dizziness, fatigue, tremor, weight gain

12. HRT Counselling about risks and benefits Contraindications to HRT
Different routes/types of HRT
Deciding on appropriate HRT (systemic or local)
Following up patients on HRT
Stopping HRT

13. Benefits of HRT Proven Relief of menopausal symptoms
Prevention/treatment of osteoporosis
Reduced risk of colorectal cancer

14. Risks of HRT Breast cancer VTE
Increased by 26% in ♀ > 50 years taking combined HRT for > 5 years
Returns to baseline 5 years after stopping
VTE
2-3x with oral HRT, highest in first year
Absolute risk remains small
 risk of acute coronary events in women with pre-existing CVD in first year
 risk of CVA

15. Women’s Health Initiative
Launched in 1991
Effect of postmenopausal HRT, diet modification, and calcium and vitamin D supplements
heart disease
Fractures
breast and colorectal cancer.
Combined HRT
↑ MI, CVA, VTE, breast cancer
↓ colorectal cancer and fractures
Oestrogen alone
↔ MI, colorectal cancer
↑ CVA, VTE
? Breast cancer
↓ fractures

16. Million Women Study
National study involving over a million women aged 50 and over
Main focus is effect of HRT use
Over 1 in 4 women in target age group are in study
 risk breast cancer in women using HRT, particularly with combined HRT
 risk breast if HRT peri- rather than postmenopause
Between 1996 and 2001 women were asked to participate when they received their invitation for Breast Screening

17. Contraindications to HRT * specialist initiation
Hormone dependent cancer – endometrial cancer, current or past breast cancer*
Active or recent arterial thrombotic disease (CVD, CVA)*
VTE*
Otosclerosis*
Severe active liver disease (oral oestrogen)
Undiagnosed breast mass
Undiagnosed abnormal vaginal bleeding
Dubin-Johnson and Rotor syndromes

18. Relative contraindications
May require extra supervision
Uterine fibroids
Endometriosis
Hypertension
Migraine

19. HRT Local symptoms Vaginal oestrogen Systemic symptoms Uterus
No uterus
Combined HRT
Oestrogen only
Oral or non-oral
Perimenopausal
Postmenopausal (>12 months since LMP)
Sequential or cyclical HRT
Continuous combined HRT (no bleeds)
Tibolone

21. Local symptoms
Vaginal dryness, soreness, dyspareunia, urinary frequency/urgency
Various preparations
Pessaries e.g. Ortho-Gynsest®
Creams e.g. Gynest ®, Ovestin ®
Tablets e.g. Vagifem ®
Rings e.g. Estring ®
Some damage latex condoms/diaphragms

22. Non-oral oestrogens All estradiol 17 beta
Avoid first pass metabolism in liver
Available as
Patches
Gels (less irritating than a patch)
Implants (last resort)
Low, medium and high doses
Potentially more suitable for women:
With liver disease or gallstones
At risk of VTE
With DM and others with raised TGs
On enzyme inducers
First line for women with migraine and malabsorption

23. Oral oestrogens Three types Low, medium, high doses Start at low dose
Conjugate equine oestrogens (CEEs)
Estradiol 17 beta
Estradiol valerate
Low, medium, high doses
Start at low dose

24. Progestogens – three types
Testosterone analogues (C19 - androgenic SEs)
Norethisterone, levonorgestrel (Mirena®), Norgestrel
Progesterone analogues (C21)
Dydrogesterone, medroxyprogesterone acetate (MPA)
Newer (derivates of norgestrel)
Desogestrel, norgestimate, gestodene
Mirena® is licensed for endometrial protection alongside oestrogen replacement for up to 4 years.

25. Why bother about type?
Oral (combined or alone), transdermal (combined) and intrauterine
If patient gets PMS-type symptoms
Can alter progestogen to less androgenic type
Can alter route of progestogen (e.g. to IUS)

27. HRT Local symptoms Vaginal oestrogen Systemic symptoms Uterus
No uterus
Combined HRT
Oestrogen only
Oral or non-oral
Perimenopausal
Postmenopausal (>12 months since LMP)
Sequential or cyclical HRT
Continuous combined HRT (no bleeds)
Tibolone

28. Perimenopausal Postmenopausal
Sequential if regular period or cyclical if infrequent (Tridestra®)
Progestogen days/month
5% - 15% have no monthly bleed
Tridestra® gives 3 monthly bleed
Postmenopausal
Continuous (no bleed HRT)
Require investigation if persistent bleeding
> 6 months
Heavier bleeding
Bleeding after a period of amenorrhoea
Tibolone

29. Tibolone
Synthetic steroid that properties of oestrogen, progestogen & testosterone
For prevention of osteoporosis in postmenopausal women
For short term use in pre-menopausal ♀ being treated with GnRH
Increases risk of stroke in ♀ > 60 years, similar to conventional HRT in younger ♀

30. Side Effects of HRT Nausea, vomiting, abdominal cramps, bloating
Weight changes
Breast tenderness
PMS-like syndrome
Sodium and fluid retention
Glucose intolerance
Altered blood lipids
Mood changes
Headache, migraine, dizziness
Leg cramps
And more…

31. Testosterone?
Women who have had TAH+BSO may experience testosterone deficiency (abrupt rather than gradual fall in levels)
Can offer replacement
Implants (need to monitor levels before each change)
Patches
SEs: hirsutism, deep voice, clitomegaly
Must be on oestrogen, but not CEE

32. Questions to ask… Does patient want HRT?
Is the patient informed about risks and benefits?
Are symptom local or systemic?
Does the patient have a uterus?
Is the patient peri- or postmenopausal
Which oestrogen?
Which progestogen?

34. Premature menopause Classification
Normal: 45 – 55 years (average 51 years)
Early: 40 – 45 years
Premature: < 40 years
Unpredictable, so need to continue contraception
Diagnosis
Minimum of two FSH >30 iu/L at least one month apart

35. Other Investigations Pregnancy test! TFTs
Prolactin for hyperprolactinaemia
Auto-antibodies (ovarian/thyroid/adrenal)
Karyotyping if < 30 years for mosaic Turner’s Syndrome
Baseline DEXA, then repeat every years
Baseline fasting lipids (yearly, depending on RFs)
Follicle tracking on USS (fertility)

36. Risks of premature menopause
Life expectancy is reduced (2 years)
Untreated,
50% higher risk of osteoporotic fracture between years
 risk of CVD compared to woman of same age
260%  risk of dementia following removal of a single ovary by age 38
 risk Parkinson’s

37. Treating premature menopause
Oestrogen replacement with progesterone
Given most conveniently as COCP
Continue until aged 50 years

38. Follow up on HRT Three monthly until stabilised, then yearly
At follow up, check:
Symptom control
bleeding control
Side effects
BP, BMI
Reassess risk vs. benefits
Breast awareness

39. Duration of use Minimum dose for shortest period
Symptoms last between 2-5 years, so try stopping at 3-5 years
Woman can continue longer as counselled re risks…

40. Stopping
Ensure progestogen dose offers endometrial protection if ↓ing slowly (high dose oestrogens only)
No evidence of how best to stop i.e. gradual versus sudden
When stopping HRT, warn patient of 2-3 months rebound vasomotor symptoms

41. HRT Sudden severe chest pain Sudden dyspnoea
Unexplained swelling/severe calf pain
Severe stomach pain
Neurological effects
Hepatitis, jaundice, hepatomegaly
Systolic BP > 160, diastolic >95 mmHg
Prolonged immobility
Detection of RF that is contraindication
Stop 4-6 weeks before any major surgery

42. Summary
HRT is good for menopausal symptoms and osteoporosis prevention
Non-hormonal treatments can help with symptoms
HRT is not necessarily systemic
Treatment must be regularly reviewed

43. Stopping contraception around the menopause - 1
Contraception may be stopped at 55 years
Women using hormonal contraception, and have regular bleeding at 55 years should continue with contraception
Ideally women over 50 years should switch to POP, implant, LNG-IUS or barrier method until aged 55, or until menopause confirmed

44. Stopping contraception around the menopause - 2
FSH is not a reliable indicator of menopause in women using combined hormonal contraception
Women with premature menopause may need specialist contraceptive opinion (ovarian activity may return spontaneously)

45. Stopping contraception around the menopause - 3
If using non-hormonal methods of contraception,
Women over 50 years can stop after 1 year of amenorrhoea
Women under 50 years can stop after 2 years
Women over 40 yeas with a copper IUD (≥ 300 mm2 copper) inserted at or over age 40 can retain the device until the menopause
FSH is best used in women aged over 50 on progestogen only methods
Need 2 x FSH ≥ 30iu/L, 6 weeks apart, and then contraception can be stopped after a year

46. HRT and Contraception Women should not rely on HRT for contraception
POP can be used to provide contraception with combined HRT
Women using oestrogen replacement may use LVG-IUS (Mirena®) to provide endometrial protection.
When IUS is used as progestogen component, it must be changed no later than 5 years (license says 4 years)

47. Resources eLFH learning modules
Menopause and HRT InnovAiT, Vol.2, No. 1, pp 10 – 16, 2009.
Common problems of the menopause InnovAiT first published online May 16, 2012 doi: /innovait/ins075
FSRH Guidance: Contraception for women ages over 4o years (July 2010)

48. QUIZ

49. Question 1
Which one of the following conditions is least likely to be the cause of post menopausal bleeding?
Atrophic vaginitis
Cervical intraepithelial neoplasia (CIN)
Hormone replacement therapy
Tamoxifen therapy
Urethral caruncle

50. Question 2
The age at which a woman reaches the menopause is related to:
Age at menarche
Ethnic group
Family tendency
Parity
Regularity of cycle

51. Question 3
A 52-year-old post-menopausal woman comes to see you regarding her menopausal symptoms. She is suffering with intrusive hot flushes and these vasomotor symptoms are getting her down. She does not want to take HRT but would consider another medicine, if it would help.
Which one of the following have an evidence base for its use in this situation?
Amitriptyline
Flupentixol
Mirtazapine
Phenelezine
Venlafaxine

52. Question 4
A post-menopausal woman comes to see you complaining of frequent intrusive hot flushes. She does not wish to take HRT and is keen to try 'natural alternatives'.
Which one of the following alternatives has the most evidence base for its use in this situation?
Dong quai
Evening primrose oil
Ginkgo biloba
Kava kava
Red Clover

53. Question 5
A 54-year-old lady comes to see you to discuss treatment for the menopause. Her last period was 18 months ago. She has no significant past medical or surgical history and is keen to try HRT as she is getting troublesome hot flushes and vaginal dryness.
Following full discussion and counselling she has no contraindications to hormonal treatment and is keen to try a suitable regimen.
Which one of the following is the most appropriate to prescribe?
Continuous combined HRT
Low dose COCP
Oestrogen only HRT
Sequential HRT
Topical vaginal oestrogen

54. Question 6
A 52-year-old lady comes to see you. Her periods had become light and infrequent for several years and then stopped about five months ago. She has no other significant past medical or surgical history.
Her family history reveals no significant cardiovascular or thromboembolic disease. She is a lifelong non-smoker. She has had two pregnancies both of which resulted in healthy children.
She currently feels well. On further questioning she has had some mild flushes but these are not troublesome. Examination reveals a BP of 118/76 and a BMI of 22.

55. Question 6 Which of the following pieces of advice should you give?
Blood tests for FSH, LH and oestradiol should be sent to confirm she is post-menopausal and guide her management
Her periods have become irregular and ceased because of waning oestrogen production, and that HRT is indicated as it will counteract this and help with the flushes
If she is worried about pregnancy risk then a low dose COCP would be her best option, as it would treat her flushes as well as provide contraception
She is postmenopausal and therefore does not require any contraception
She is probably postmenopausal but she should continue to use contraception until 12 months have elapsed since her last period

56. Question 7 Menopausal assessment Symptoms but does not wish HRT:
Clonidine
(I)
Gabapentin
Alternative Rx
Decision to start HRT
Urogenital symptoms only (II)
Systemic HRT
With uterus
Without
uterus
Post-menopausal
Peri-menopausal
III IV
Regular cycle
Infrequent cycle V VI

57. Question 7 Management of menopausal symptoms algorithm
A – alendronate
B – beta blockers
C – continuous combined oestrogen
D – danazol
E – local oestrogens
F – long cycle HRT
G – selective serotonin reuptake inhibitor
H – sequential HRT
I – strontium ranelate
J – systemically absorbed oestrogens
For each of the following stems relating to key points in the algorithm, select the correct option to complete the algorithm from the list given.
Each option may be used once, more than once or not at all.

58. Question 8 Which one of the following is true of the menopause?
All symptoms respond to counselling
Flushes should not be treated with systemic oestrogens
Hormone profiles are needed for confirmation in most cases
Hot flushes may respond to clonidine
Loss of libido is due to oestrogen withdrawal
Phyto-oestrogens are as effective as HRT
Tibolone is not effective for loss of libido

59. Question 9 A – Clonidine B - Combined hormone replacement
For each case below, choose the single most appropriate treatment from the given list of options. Each option may be used once, more than once, or not at all.
A – Clonidine
B - Combined hormone replacement
C - Dietary modification
D - Hypnotic preparations
E - Mineral supplements
F - Oestrogen only HRT
G - Psychological support
H - Referral to psychiatrist
I - Regular exercise
J - Vaginal lubricant
K - Vaginal oestrogens therapy (HRT)

60. Question 9
A 52-year-old married woman who has a family history of breast cancer has been experiencing mild dyspareunia for a few hours following intercourse for the last month. She is worried about using hormones.
A 45-year-old woman who has had a total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) for fibroids and menorrhagia complains of hot flushes, night sweats and mood swings. She has no other medical problems
A 72-year-old woman has experienced frequency of micturition intermittently for the last few months. Mid-stream urine (MSU) cultures have been persistently negative. She is well otherwise, but would like the symptoms resolved.
A 56-year-old woman whose periods stopped five years ago has become increasingly depressed. She now feels life is no longer worth living and threatens suicide.

61. END