PRESENTATION ON THE PHYSIOLOGY OF MENOPAUSE

1. PHYSIOLOGY OF MENOPAUSE
By
Chidiebere Agbo
(Registrar, REF Unit)
24th August, 2022
1

2. OUTLINE
• Introduction
• Relevant terminologies
• Epidemiology
• Menstrual cycle
• Physiology of menopause and clinical correlation
• Psychological and Sociocultural impact
• Conclusion
• References
2

3. YOUNGER WOMAN AND OLDER WOMAN
3

4. INTRODUCTION
• Greek words : Menos (month) & pausis (cessation).
• End of monthly/menstrual cycle.
• Cessation of period following the loss of ovarian activity and absence of ovarian
estrogen secretion
4

5. INTRODUCTION (CONT’D)
• Begins after 12 months of amenorrhea after the final period.
• It marks the end of fertility when the woman will not be able to bear further
child without any form of assisted methods of conception.
• It is a retrospective diagnosis
• Manifests by medical, psychological and emotional conditions
• 1887 menopause was documented as a cause of mental problems
5

6. INTRODUCTION CONT’D)
• Menopause can be natural or induced (artificial)
• Natural- is a gradual process
• Induced (artificial)- Permanent cessation of ovarian function by artificial
means
• Unlike menarche which is influenced by many biological and environmental
factors, only a few factors such as smoking and malnutrition have been
documented to be associated with early menopause
6

7. RELEVANT TERMINOLOGIES
• Commonly used interchangeable terminologies assumed to mean
same but strictly two different entities are two stages in a woman’s
life termed Climacteric and perimenopause.
7

8. CLIMACTERIC
• Klimakter (Greek)- rung of ladder. Major movement on life’s ladder.
• It is the period of time during which a woman passes through reproductive to
non reproductive stage.(45-55yrs)
• Wide variety of symptoms, signs, metabolic adjustment.
• Ultimate cause of which is a major reduction in level of circulating oestrogens
8

9. PERIMENOPAUSE
• It is 3-5 years preceding menopause with increase frequent irregular
anovulatory bleeding followed by episodes of ammenorrhea and intermittent
menopausal symptoms.
• It stops 1 year after menopause.
9

10. PREMATURE MENOPAUSE/PREMATURE OVARIAN FAILURE
• Cessation of menses before 40 years of age –
• Cessation of menses and development of climacteric symptoms and
complaints can occur as early as a few years after menarche
Causes:
• Idiopathic
• Genetic – Turner’s syndrome
• Fragile x .
• FSH receptor polymorphisms
10

11. EARLY MENOPAUSE
• Cessation of menses at < 45 years of age
• Majorly, iatrogenic
11

12. DELAYED MENOPAUSE
• Condition in which menstruation extends beyond 55 years.
• Late menopause occurs in women with estrogenic tumour of the ovary,
women with endometrial cancer, high socioeconomic status.
• Often it is constitutional.
• Endometrial biopsy is required to rule out endometrial pathology
12

13. EPIDEMIOLOGY OF MENOPAUSE
13

14. EPIDEMIOLOGY OF MENOPAUSE (CONT’D)
• African women: 3 studies
• 48.4(48.1-48.6)
• Nigerian and Ghanaian studies: 48-49.5
14

15. BRIEF EMBRYOLOGY
• Oocytes
• Process begins in embryonic life.
• 20 weeks gestation - 6 - 7 million follicles.
• At birth - 1-2 million follicles
• Puberty: 300 000 – 500 000
• Ovulation accounts for 500 with atresia of others with age
• Depletion of oocytes eventually leads to cessation of menstruation which is the
cardinal sign of menopause
15

16. EMBRYOLOGY (CONT’D)
• Follicular loss accelerates when the total number of follicles is ~25,000
• When follicles are sufficiently depleted (<1000), menopause occurs
• There are 2 landmarks in ovarian failure process:
Marked decline in fertility with no cycle dysfunction
Cycle changes with shortened follicular phase, and luteal phase dysfunction
16

17. MENSTRUATION
• Defined as a periodic cyclical shedding of the progestational endometrium
accompanied by blood
• The menstrual cycle is the interval between two successive menstruation
17

18. HPO AXIS
18

19. PHASES OF FEMALE REPRODUCTIVE YEARS
19

20. ENDOCRINE CHANGES IN MENOPAUSE
• Estrogens; Fall in estradiol & estrone
• Androgens; fall in androstenedione, testosterone, DHEA & DHEAS
• Progesterone falls
• Gonadotropin; Rise in LH & FSH
• Others; fall in AMH & Inhibin B
20

21. ENDOCRINE CHANGES (CONT’D)
• Estrogen
• The follicle is the basic functional unit of the ovary.
• It is composed of an oocyte, granulosa cells, and theca cells.
• The bulk of Estrogen in premenopausal women is Estadiol(E2)
21

22. ENDOCRINE CHANGES (CONT’D)
• Main postmenopausal oestrogen is estrone (E1) produced by peripheral fat
from adrenal androgen by aromatization.
• Synthesis principally from androgens to E2 in granulosa cells. Aromatase
enzymes promoted by FSH.
• At menopause dramatic decrease of estrogen→menstruation ceases and
symptoms of menopause start.
22

23. ENDOCRINE CHANGES (CONT’D)
• Theca cells produce oestrogen from androgens stimulated by
LH.
• 1st sign of approaching menopause is decline in fertility in 4th
decade.
• 1st endocrine change is fall in inhibin production by ovary
• Inhibin is a glycoprotein that inhibits production of FSH
23

24. ENDOCRINE CHANGES (CONT’D)
• Progesterone:
• Major source is the corpus luteum premenopause.
• Postmenopausal level is only 30% of young women during follicular phase.
• Level remains very low.
• Main source – adrenal gland.
• Mean level -0.4ng/ml (0.2 – 7)
• Measurement is of no clinical use.
24

25. ENDOCRINE CHANGES (CONT’D)
• Gonadotropins
• FSH → 10 – 20 fold increase > 40 lU/L .
• L H → 3 fold increase
• (Due to absent negative feedback effect of estradiol
and inhibin)
• FSH rises earlier than LH 25

26. ENDOCRINE CHANGES (CONT’D)
• Most significant change in the hormonal profile is the
dramatic decrease in circulating estradiol
• Ovarian stromal and adrenal glands secrete
androstenedione which is aromatized to estrone
become source of estrogen
26

27. ENDOCRINE CHANGES (CONT’D)
27

28. ENDOCRINE CHANGES (CONT’D)
28

29. EFFECT OF ENDOCRINE CHANGES
• Shorter menstrual cycles <25 days due to a shortened follicular phase
(e.g., 10 days rather than 14) but luteal phase remains fairly constant
• Transition to progressive periods of anovulation and unpredictable
menstruation.
• Amenorrhea occurs once the follicular pool is depleted, at which point
FSH levels remain persistently elevated for the remainder of the
woman's life
29

30. MENOPAUSAL CHANGES
• Nervous system (vasomotor changes)
• Reproductive system
• Urinary system
• Cardiovascular system
• Musculoskeletal system (bone metabolism and osteoporosis)
30

31. MENOPAUSAL CHANGES (CONT’D)
• Skin and hair
• Breast
• Metabolic changes
• Cognitive dysfunction
• Psychological aspect
• Sociocultural impact
31

32. VASOMOTOR CHANGES
• The classical vasomotor symptom that has been observed in women is
the hot flush
• Exact mechanism unknown
• Symptoms result from a defect in central thermoregulatory function
• Changes in CNS concentrations of norepinephrine and serotonin likely
play an important role
32

33. VASOMOTOR CHANGES CONT’D
• Close temporal association between the occurrence of flushing
and the pulsatile release of LH has been demonstrated.
• Vasomotor symptoms are a greater annoyance than most
physicians recognize.
33

34. MANIFESTATION OF HOT FLUSHES
• Reported in as many as 80% of women.
• Short-lived sensation of intense heat with sweating in the upper body.
• Associated with flushing, anxiety, and tachycardia and can be
debilitating
34

35. HOT FLUSHES
35

36. CHANGES IN REPRODUCTIVE TRACT
36

37. CHANGES IN URINARY TRACT
37

38. CVS CHANGES
38

39. MUSCULOSKELETAL SYSTEM (BONE
METABOLISM AND OSTEOPOROSIS)
• Increased receptor activator of nuclear factor-κB ligand (RANKL) levels
• Leads to osteoclast activation and increased bone resorption.
• Decreased production of osteoprotegerin (OPG), an osteoclast inhibitor
• compounded by general age-related changes in bone metabolism and
remodeling
• Disturbed vitamin D and calcium homeostasis
• Less mechanical stimulation of bone turnover
39

40. OSTEOPOROSIS
40

41. MUSCULOSKELETAL SYSTEM (BONE
METABOLISM AND OSTEOPOROSIS)
41

42. SKIN AND HAIR CHANGES
• Loss of elasticity
• Skin becomes thinner and wrinkles (around the mouth and eyes: the so-
called “Purse string” and “Crow feet” respectively) become evident
42

43. CHANGES IN BREAST
• Regression of breast size during and after menopause
• This is psychologically distressing to some women
• Could be of benefit for those with cyclic symptoms of breast pain and
cyst formation
43

44. METABOLIC CHANGES IN
MENOPAUSE
• Higher prevalence of obesity in postmenopausal women
• Multifactorial process
• Reduced energy expenditure due to physical inactivity
( compounded by depression)
• Muscle atrophy and a lower basal metabolic rate
• Redistribution of body fat from the periphery to the trunk, which results
in visceral adiposity.
44

45. METABOLIC CHANGES (CONT’D)
• Abdominal obesity and menopausal oestrogen decline are associated
with insulin resistance, a propensity to develop type 2 diabetes mellitus
and dyslipidemia
• Dyslipidemia characterised by low (HDL) cholesterol levels and a high
(LDL) particles.
• Altered adipokine secretion, which leads to chronic inflammation, is a
possible mechanism that links abdominal obesity to its metabolic
consequences
45

46. METABOLIC CHANGES
46

47. COGNITIVE DYSFUNCTION IN
MENOPAUSE
• Estrogen increase cellular proteins, promote neuronal growth and survival,
neural transmission and function, and synaptogenesis
• The menopausal transition has also been linked to changes in cognitive
function
• CNS (prefrontal cortex, hippocampus and striatum) that control learning,
registering and retrieving information, judgment, evaluation processes and
language skills.
47

48. COGNITIVE CHANGES (CONT’D)
• Limitation of the inflammatory response in the CNS, which helps to
avoid repeated inflammatory insults (dystrophy dementia).
• Aspects related to verbal memory and verbal fluency are most affected
• Simply a manifestation of depression
• Consequence of sleep having been disrupted by hot flushes
48

49. PSYCHOLOGICAL ASPECT OF
MENOPAUSE
• Climacteric and menopause exemplify interplay between biological and
social factors.
• Menopausal disorders are not yet recognized as an entity in clinical
psychiatry
• Categorized under psychophysiological disorders group.
• Symptoms such as anxiety, despair, depression and estrangement.
49

50. PSYCHOLOGICAL ASPECT OF
MENOPAUSE CONT’D
50

51. SOCIOCULTURAL IMPACT
• Devalued or valued
• Myths and beliefs
• New marriages
• Marital discord
51

52. SOCIOCULTURAL IMPACT CONT’D
• Value ; some communities place them on the same level as men and view
them as being capable of taking decisions
• Devalued; setting aside by spouse as reproductive function ends
• Marital discord as a result of the woman’s belief that she shouldn’t engage
in sexual activity
• Sexual intercourse with menopausal women sap the man’s energy, make
them ill and weak
• Sexual intercourse causes abdominal distention as they believe there is no
outlet for ejaculate
• New marriages by men once the older wives are menopausal
52

53. SUMMARY OF THE PATHOPHYSIOLOGY
OF MENOPAUSE
53

54. STAGES OF REPRODUCTIVE AGING
WORKSHOP (STRAW)
STRAW
-This is Staging of Reproductive Aging Workshop.
• The STRAW staging system is widely considered the gold standard for
characterizing reproductive aging through menopause
• First postulated in 2001
• Revised in 2011 ( STRAW +10) more inclusive
54

55. STRAW (CONT’D)
• Goal
- provide consistent classification criteria for menopause clinical and
research agendas
- assessment of fertility, contraceptive needs, and healthcare
- decision making.
- To identify knowledge gaps that should be addressed by the
research community
55

56. STRAW (CONT’D)
• The STRAW+10 added more criteria using endocrinological
parameters such as FSH, AMH, Inhibin B, menstrual cycles,
symptoms such as vasomotor, urogenital, fertility capability, ovarian
imaging including AFC.
• There are both inclusion and exclusion criteria
56

57. STRAW (CONT’D)
• Exclusion criteria:
• - Women who had hysterectomy or endometrial ablation.
- Women with chronic menstrual irregularity such as PCOS.
-Women with chronic illness such as HIV/AIDS.
-Women undergoing chemotherapy
57

58. STRAW (CONT’D)
• STRAW divided the female life into 3 broad phases:
-Reproductive phase (3)
-Menopause transition(2)
-Postmenopause(2)
• The 3 phases contain 7 stages: 3 for the reproductive phase, 2 for the
menopausal phase, and 2 for the postmenopausal phase.
58

59. STRAW CONT’D
59

60. CONCLUSION
• Menopause is a normal life event
• Knowledge of its physiology is crucial in enlightening our women
• This could be enough to allay fears in them.
60

61. •THANKS FOR
LISTENING
61

62. MANAGEMENT OF MENOPAUSE
A PRESENTATION BY
DR. OLANREWAJU PETER FATOKI
REGISTRAR
REF UNIT
24TH AUGUST 2022

63. OUTLINE
• INTRODUCTION
• CLASSIFIACTION OF MENOPAUSE
• MANAGEMENT
• CONCLUSION
• REFERENCES
63

64. INTRODUCTION
• It is said that everything has a beginning and an end, so do physiological cycles
• It is only normal that females experience Menarche and Menopause and this
presentation centers on Menopause
• Menopause is defined as the last menstrual period after a minimum of 12months
amenorrhea.
• Regardless of if natural or induced, the signs and symptoms are the same.
• The age of occurrence is genetically predetermined, averagely by 51years but within
the range of 45 – 55years. Nigerian and Ghanaian studies put it as 48 – 49.5years
(Kwawukume et al)
64

65. CLASSIFICATION OF MENOPAUSE
• Menopause can be classified based on cause into;
• Natural Menopause
• Premature menopause/Early Menopause/POI
• Induced Menopause
65

66. CAUSES OF NON INDUCED PREMATURE MENOPAUSE/POI
S/No Causes Examples
1 GENETIC Turner syndrome (XO 45) or mosaic turner (45X/46XX), Trisomy X (47XXX
or Mosaic, FMR1 (fragile X Mental retardation 1) premutation
Other chromosomal abnormalities: mutations of FOXL2, NR5A1, BMP15,
FSHR and Gs alpha genes and of steroidogenic enzymes
2 METABOLIC Galactose-1-phosphate uridyltransferase deficiency
Carbohydrate-deficient glycoprotein deficiency
17 alpha-hydroxylase 17,20 desmolase deficiency mutations of the
aromatase gene
3 AUTOIMMUNE Polyglandular autoimmune syndrome, Hypothyroidism, Type1 Diabetes
mellitus, Myaesthenia gravis, Systemic lupus erythematosus, Addison’s
disease, Thrombocytopenic purpura, vitligo, Alopecia, pernicious anemia or
autoimmue anemia, Rheumatoid arthritis, Crohn’s disease, sjogren’s
syndrome, Primary biliary cirrhosis
4 INFECTIOUS Viral infections (HIV, Varicella), Tuberculosis, Shigellosis, Malaria
5 OTHERS Women of Chinese race or Hispanic origin
66

67. CAUSES OF INDUCED MENOPAUSE
• Bilateral Oophorectomy
• Bilateral Ovarian cystectomies
• Chemotherapy: Primarily, alkylating agents and anthracyclines
• Radiation-external beam or intracavitary
• Environmental toxins (Tobacco, dioxins)
• Pelvic vessel embolization
67

68. GENERAL OVERVIEW OF MANAGEMENT
• The management of menopause may be multidisciplinary sometimes and it more
importantly entails;
• Taking a detailed history
• General and physical examinations
• Investigations
• Diagnosis
• Treatment
68

69. HISTORY
• Must be detailed. The use of a check list is helpful
• Important notes include
• Age
• Race/ethnicity/geographical location
• occupation
• Parity
• Presenting complaints - irregular menses, amenorrhea, hot flushes e.t.c
• Surgical history - TAH + BSO, Oophorectomy e.t.c
• Drug history
• Comorbidities
69

70. EXAMINATION
• A thorough examination is of the essence
• General and physical examination findings will help rule out possible
differentials and comorbidities which may be associated with a menopausal
state
• All systems are to be examined
70

71. INVESTIGATIONS
General investigations Specific investigations others
FBC/CBC
Serum E/U/Cr
Urinalysis
Hormone profile (FSH, LH,
estrogen, progesterone and
AMH)
Thyroid stimulating hormone
24hour urine calcium/cr
Serum lipids
Abdominopelvic USS
Electrocardiogram (ECG)
Vaginal smears
Endometrial/cervical smears
71

72. DIAGNOSIS
• The diagnosis of menopause is said to be retrospective
• Like earlier stated, a detailed history, general and physical examination and
investigations help in the conclusion of such diagnosis ruling out all other
differentials and comorbidities
• Once the diagnosis is made it informs treatment decisions/options
72

73. TREATMENT
• Following proper counselling, treatment options are:
• Counselling
• Non Pharmacological
• Pharmacological
• Hormonal
• Non-Hormonal
73

74. TREATMENT CONT’D
• The first aspect of treatment is COUNSELLING. A vital process in the management
of menopause
• It helps resolve some concerns of menopausal women without resorting to
medications
• Requires patience, care, empathy and proper communication
• The focus is to educate the patient on the physiologic process, clarify doubts and
myths
• Patient must be given the opportunity to enumerate what she has learnt in her own
words
• Consider the possibility of multiple visits.
74

75. NON-PHARMACOLOGICAL
• Lifestyle:
• Exposure to sunlight,
• smoking caesation,
• reduce alcohol and caffeine intake,
• increase number baths,
• wear light clothes, no weight-bearing,
• Exercise; Brisk walking and jogging
• Dietary:
• Fortified diets (with calcium, vitamin D3 and protein), fruits,
vegetables, proper daily hydration
• Soy protein: they are helpful in relieving vasomotor symptoms
• Flouride: used in conjunction with calcium supplements. (When used
long term can lead to brittle bones)
75

76. HORMONAL TREATMENT/MENOPAUSAL HORMONE THERAPY
(MHT)
• This refers refers to Menopausal Hormone Therapy (MHT) formerly HRT
• It refers to the use of estrogen or combination estrogen/progesterone
treatment and androgens.
• For women who seek help for their menopausal symptoms, MHT is the most
commonly prescribed treatment
• It helps to relieve symptoms by replacing estrogen levels that naturally fall
during menopause
• It could be administered as tablets, skin patches or skin gels
• Patients are duly educated on the risks and benefits of MHT prior to
commencement 76

77. INDICATIONS FOR MHT
• Women having climateric symptoms
• All asymptomatic high-risk women having
• Premature menopuse(surgical/spontaneous)
• Established osteoporosis on X-ray/B.M.D measurements
• Family history of osteoporosis
• Thin, small sedentary women
• Poor diet, excess alcohol, Corticosteroid and other medications
• High urinary calcium/creatinine, Low plasma estradiol
• Asymptomatic women with/without risk factors having no contraindications
but who request MHT 77

78. ESTROGEN (MHT)
• The minimum effective dose should be used and could be increased when required
• Despite this general consensus, it is important that the dose is high enough to fully
alleviate symptoms.
• Higher doses of exogenous estrogen are associated with increased risk of breast
cancer, VTE and stroke.
• Dose and route of administration of estradiol is tailored to the requirements of the
woman to optimize benefits and minimize side effects and risks
78

79. ESTROGEN (MHT) CONT’D
• The starting doses of currently available systemic estrogen are as follows;
• 0.3mg oral conjugated equine estrogen
• 1mg oral micronized estradiol or estradiol valerate
• 25 -50ug transdermal estradiol
• Two metered doses of estradiol gel or 0.5-1.0mg estradiol sachets
• 25 – 50ug implanted estradiol (currently unlicensed for commercial use)
79

80. MHT – ESTROGEN CONT’D
• Prior to menopause, the estradiol/estrone ratio was 2:1 and this can be achieved if
estradiol is delivered transdermally, by avoiding first-pass effect
• Oral estradiol preparations are partially metabolized to estrone by hepatic first-pass
effect and so do not fully restore this ratio
• Sublingual tabs/wafer, nasal sprays are in the works. These provide room for
improved bio-availability
80

81. • VAGINAL ESTROGEN
• The most effective treatment for vulvovaginal atrophy (VVA) is local application
of estrogen but the benefits only last whilst the preparations are used
• This is achievable through creams, tablets, rings delivering estriol and estradiol
• There is no significatnt systemic absorption of oestrogen from these
formulations, therefore do not lead to endometrial hyperplasia or bleeding
problems
• Hence endometrial protection with progestogens is not required
81

82. VAGINAL ESTROGEN CONT’D
• VVA symptoms can be very distressing but are easily and safely alleviated
with vaginal estrogen
• There is a license of 10ug of estradiol vaginal tablets which gives relief to
urogenital symptoms. A year of exposure equates to 1.4mg of estradiol in
total
• Some women require higher doses to fully alleviate their symptoms. This is
indicated in the NICE guidelines but must be used judiciously
82

83. • VAGINAL ESTROGEN (MHT) CONT’D
• Local vaginal estrogen options are;
• 0.01% estriol cream and pessaries
• 0.1% estriol cream
• 10ug per 24hours estradiol vaginal tablets
• 75ug per 24 hours estradiol-releasing silicone ring
83

84. NEW OPTIONS FOR TREATMENT OF VVA
• Ospemifene
• it is a new option for treating VVA
• It is a Selective Estrogen Receptor Modulator that has estrogen-type activity in
the urogenital tract
• Used for treatment of moderate to severe dysparunia
• For women who have a history of hormone receptor-positive malignancy whose
menopause symptoms are often complicated by use of tamoxifen or aromatase
inhibitors, the avoidance of estrogen may be of advantage in 84

85. • CO2 laser & Erbium laser technology
• It is being used to rejuvenate atrophic vulval and vaginal tissue
• Done by facilitating the regeneration of collagen and eslatin through
improved blood flow
• Still a work in progress
85

86. PROGESTOGENS – MHT CONT’D
• This is required in women using systemic estrogen to minimize the risk of
endometrial hyperplasia and carcinoma
• If the last menstrual period occurred less than 1year prior to starting HRT,
sequential combined regimen is recommended. (i.e estrogen with progesterone
for 12days per cycle)
• A progesterone challenge is required after 3months of estrogen alone in women
who have had subtotal hysterectomy to check for residual endometrial tissue. An
USS could be used
• Low dose progesterone is also used after endometrial ablation and pelvic
radiotherapy. It’s considered for women following hysterectomy for severe
endometriosis 86

87. PROGESTOGENS – MHT CONT’D
Generatio
n
Progestin Estrogenic Progestational Androgenic
First Norethindrone
Ethynodiol diacetate
Norgestrel
Norethindrone
acetate
++
++
-
++
++
+++
+++
++
++
+
+++
++
Second Levonogestrel - ++++ ++++
Third Norgestimate
Desogestrel
-
+/-
++
++++
++
++
Fourth Drospirenone - +/- -
87

88. MINIMUM DOSES OF PROGESTERONE GIVEN ORALLY IN MHT AS
ENDOMETRIAL PROTECTION
Progestogen type Sequential combined daily dosage Continuous combined daily dosage
Testosterone-derived
progestogens
Levonorgestrel 75ug N/A
Levonorgestrel intrauterine system N/A 20ug
Norgestrel 150ug 50ug
Norethisterone 5mg 0,1mg
Progesterone-derived
progesterons
Crpterone 2mg 1mg
Medroxyprogesterone acetate 5mg 2.5mg
Micronized progesterone 200mg 100mg
Cyclogest pessaries 400mg 200mg
Crinone gel (8%) Alternate days/12days/cycle Twice weekly 88

89. PROGESTOGENIC SIDE EFFECTS
• The main factor for reduced compliance is that of progesterone intolerance
• Progestogens have numerous effects different from the one for which their use was
intended
• Fluid retention - sodium retaining effect of the RAS triggered by stimulation of
aldosterone 1 receptor
• Androgenic - Acne and hirsutism from testosterone-derived progestogen,
stimulation of androgen receptors
• Mood swings - from stimulations of the CNS progesterone receptors
• PMS-like effect - from stimulation of CNS progesterone receptors 89

90. PROGESTOGENIC SIDE EFFECTS – CONT’D
• Minimizing the progestogen side effects is possible
• Dose can be halved and duration of progestogen use reduced to 7 -10days
• Natural progestogens can be used; have fewer side effects due to receptor specificity.
• MHT regimens with natural progesterone minimize metabolic impact and reduce risk
of VTE
• LIUS; recommended for endometrial protection for up to 5years, minimizes systemic
side effects by direct release of progesterone to the endometrium
• Drosperidone, a spironolactone analogue, also contains low dose estrogen. It is
progesterone receptor specific and has anti-androgenic and anti-aldosterone effects.
90

91. BIO-IDENTICAL MHT
• Estradiol, progesterone and testosterone exist in precise duplicates as
synthesized by the human ovaries
• These are bio-identical hormones
• Manufactured from plant sources
• available in micronized oral tablets, transdermal patches, implants, gels
91

92. MHT CONT’D - ANDROGENS
• Women with low sexual desire and tiredness should be counselled about the
possibility of using androgen supplementation
• Trostan 2% gel, a testosterone male gel can be use on alternate days to
achieve physiological levels
• 1% testosterone cream (AndroFeme) can also be used
92

93. MHT CONT’D - ANDROGENS
• In the administration of testosterone, the free androgen index should be
kept within the physiological range (<5.0%). At this state there is rarely any
side effects
• DHEA-S which is the sulfated form of DHEA which can be converted by
tissues in the body is used to tackle the problems of ageing and has shown
benefits on the skeleton, cognition, well-being, libido and the vagina
93

94. MHT CONT’D
94

95. BENEFIT –RISK BALANCE OF MHT
• Coronary heart disease and overall mortality
• The Women Health Initiative (WHI) study earlier claimed that there was an
increase risk in CVD, stroke, breast CA in women regardless of the age group
• Study was criticized due its design and age of subjects recruited for the study
(63years) and many with obesity, hypertension and ore-existing CVD
95

96. BENEFIT –RISK BALANCE OF MHT CONT’D
• The recent evidence supports the fact that estrogen therapy may be
cardioprotective if commenced around the window of opportunity( time of
menopause) and may be harmful if commenced 10years after menopause
• A 13year follow up of women in the WHI study, with ages between 50 -
59years showed reduction in CHD and MI
• Cochrane analysis shows that women within 10years of menopause had a
reduction in all-cause mortality of 0.70 and cardiovascular mortality of 0.52
96

97. BENEFIT –RISK BALANCE OF MHT CONT’D
• Stroke
• The Incidence may be increased when HRT is initiated in women over 60years
• From the WHI study and cochrane analysis, Initiation of HRT in women less
than 60years of age or less than 10years menopause has no effect on the risk
of stroke
• The risk of ischaemic stroke with HRT is related only to standard-dose oral
therapy,
• Low-dose transdermal therapy has a very low risk of ischaemic stroke
97

98. • Venous thromboembolism (VTE)
• During the first year of estrogen use, with or without progestogen, the
incidence of VTE is higher
• Initiation of hormone therapy in older women and continued use of such
therapy is associated with an increased risk compared to non-users
• According to the WHI study there is a slightly higher risk of VTE in women
aged 50 – 59years who used estrogen—progestogen than those who use just
estrogen, though both are far less than the risk of VTE in normal pregnancy
• Transdermal estrogen does not increase the risk of VTE
98

99. BENEFIT –RISK BALANCE OF MHT CONT’D
• Cognitive function and dementia
• If HRT is commenced post onset of dementia, it doesn’t improve cognition or slow
down disease
• HRT commenced after midlife increases the risk of dementia
• HRT commenced during midlife reduces the risk of dementia and Alzheimer's
disease (some form of prevention when commenced during the window of
opportunity)
99

100. BENEFIT –RISK BALANCE OF MHT CONT’D
• Breast Cancer
• The relationship between breast cancer and HRT is still very debatable
• The WHI estrogen and progestogen trial and several observational studies have
reported an increased risk after at least 5years of use, suggesting a possible
promoter effect on tumours
• a meta-analysis of data by the NICE guideline group says the degree for estrogen
and progestogen combined was an extra 5 per 1000 women over 7.5year period
• HRT using estrogen alone has a neutral impact on breast cancer risk according to
most studies and a possible reduction in risk 10
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101. BENEFIT –RISK BALANCE OF MHT CONT’D
• Ovarian Cancer
• There are controversies as to whether HRT increases the risk of ovarian cancer
• A meta analysis of data from 52 studies involving women age 50 – 54years;
• The absolute risk was 1 per 1000women per year of use
• A base rate of 1.2 per 1000 per 5years
• Absolute excess of 0.55 per 1000 per 5years
• Further good quality data still needed for definitive statements.
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102. BENEFIT –RISK BALANCE OF MHT CONT’D
• Osteoporosis
• MHT decreases the incidence of all fractures, even in women with high risk of fractures
• It is the only therapy available with proven efficacy of fracture reduction in women with
osteopenia
• Age at initiation of MHT is key for its efficacy
• Women 50 – 60years or within 10years after menopause, the benefits of MHT outweighs
risk and can be considered as first line therapy
• For those over 60years, bisphosphonates should be considered. If MHT is to be
considered, then the minimum effective dose should be used with estrogen delivered
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103. CONTRAINDICATIONS TO HRT
• Women with active Cardiovascular Disease, active liver disease
• Women with recent Stroke
• Women with Venous thromboembolism (though transdermal route may be considered)
• Women with known or suspected estrogen-sensitive malignant conditions
• Recent or active Arterial thromboembolic disease (angina, myocardial infarction)
• Porphyria cutanea tarda
• Undiagnosed genital bleeding
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104. PHARMACOLOGICAL (NON-HORMONAL TREATMENT)
• Selective estrogen receptor modulators (SERM): improve bone mineral
density and reduce the risk of endometrial and breast cancers. they increase
the risk of VTE
• Clonidine: centrally acting alpha-2 agonist, indicated for hot flushes
• Gabapentin: decreases hot flushes but may cause sedation
• Thiazides: reduces calcium secretion from the kidneys
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105. PHARMACOLOGICAL (NON-HORMONAL TREATMENT)
• Tibolone: synthetic steroid with estrogenic, progestogenic and androgenic
properties. Improves sexual function/libido
• Vitamin E suppository: Indicated for vaginal atrophy
• Bisphosphonates: Risendonate, etidronate. Used for postmenopausal
osteoporosis. Not useful as single therapy
• Phytoestrogens: lower the incidence of vasomotor symptoms, osteoporosis and
cardiovascular diseases
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106. CONCLUSION
• A good knowledge of Menopause and its associated challenges is
of utmost importance. Every woman deserves complete physical,
mental, social wellbeing even at this phase of life. Improving our
skill in the care of these women will do well to improve their life
expectancy
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107. 10
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108. REFERENCES
• D. Keith Edmonds MB, Christoph Lees MD, Tom Bourne PhD, 2018, Dewhurst’s Textbook of Obstetrics &
Gynaecology, 9th Edition, Blackwell Publishing Ltd (8e, 2012), Wiley Blackwell
• E Y Kwawukume, B A Ekele, K A Danso, E E Emuveyan, 2017, Comprehensive gynaecology in the tropics,
2nd Edition, G-Pak Ltd
• National Institute for Health and Care Excellence, 2015, Information for the public, Published 12 November,
2015
• Alan H. Decherney I Lauren Nathan, Neri Laufer I Ashley S. Roman, CURRENT Diagnosis & Treatment;
Obstetrics and Gynaecology
• UPDATE COURSES
• www.nice.org.uk
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