Discover the 5 essential steps for menopause hormone therapy, including benefits, risks, and how to make informed decisions for a smoother transition through menopause.

1.  Immediate Past Chairperson –Indian College of
OB/GY-ICOG
 National Corresponding Editor-Journal of
OB/GY of India JOGI
 National Corresponding Secretary- Association
of Medical Women, India
 Joint Secretary-Indian Menopause Society
 President –ISOPARB Vidarbha Chapter 2019-21
 Chairperson-IMS Education Committee 2021-23
 Chairperson-fertility enhancement Committee-
ISOPARB
 Member-SAFOG Education Committee
 President-Association of Medical Women,
Nagpur AMWN 2021-24
 Senior Vice President FOGSI 2012
 President Menopause Society, Nagpur 2016-18
 President Nagpur OB/GY Society 2005-06
Dr. Laxmi
Shrikhande
MBBS; MD(OB/GY);
FICOG; FICMU; FICMCH
Medical Director-
Shrikhande Fertility Clinic
Nagpur, Maharashtra
 Nagpur Ratan Award @hands
of Union Minister Shri Nitinji
Gadkari
 Received Bharat excellence
Award for women’s health
 Received Mehroo Dara
Hansotia Best Committee
Award for her work as
Chairperson HIV/AIDS
Committee, FOGSI 2007-2009
 Received appreciation letter
from Maharashtra
Government for her work in
the field of SAVE THE GIRL
CHILD
 Delivered 22 orations and
450 guest lectures
 Publications- 42 National
& 21 International
 Sensitized 2 lakh boys and
girls on adolescent health
issues
Awards
Positions

2. 5 steps for
Menopausal Hormone Therapy
Dr Laxmi Shrikhande
Consultant-Shrikhande Hospital & Research Centre
NAGPUR

3. U turn in Menopausal Hormone Therapy
 Widespread use of hormone therapy in the 1980s and
1990s came to an abrupt halt in the early 2000s after
initial findings of the Women’s Health Initiative trial
were published and the study was terminated
 Over the next several years, extensive re-analysis and
assessment of the WHI data cast doubt about the
validity of the original conclusions
N Engl J Med 2016; 374(9): 803–806

4. U turn in Menopausal Hormone Therapy
● In 2016, to atone for the turmoil caused by the
inappropriately communicated findings of the WHI
trials, two WHI investigators published a request for
forgiveness
N Engl J Med 2016; 374(9): 803–806

5. U turn in Menopausal Hormone Therapy
 There is general agreement among guideline groups that HT
has a favorable risk–benefit ratio in women who initiate
treatment between 50 and 59 years of age or within 10 years
of menopause onset
 In this population, HT is highly effective for relief of
vasomotor and urogenital symptoms, and can prevent bone
loss and fracture
 Symptom relief provides additional benefits such as
improved sexual function and overall quality of life (QoL)
Climacteric 2016; 19(2): 109–150
Menopause 2017; 24(7): 728–753
Minerva Ginecol 2018; 70(1): 27–34.

6. Menopausal Hormone Therapy-The timing hypothesis
 Timing of initiation of hormone therapy affects the
relation with coronary risk
 Estrogen may provide coronary benefit in early
menopause but harm if started later
 Absolute risks of hormone therapy are lower in early
than late menopause
 Hormone therapy is appropriate for vasomotor
symptom relief in early menopause
 Hormone therapy is not recommended for chronic
disease prevention
Metabolism. 2016 May ; 65(5): 794–803

7. A Step by Step Guide to MHT = HRT
Steps
Step 1 - Assess if MHT is right for the patient
Step 2 – Hormonal therapy options
Step 3 – Starting MHT treatment
Step 4 – Follow-up
Step 5 – Stopping treatment

8. Step 1
Assess if MHT is right for the patient

9. MHT indications
 Vasomotor symptoms
− Hormone therapy has been shown in double-
blind RCTs to relieve hot flashes and is
approved as first-line therapy for relief of
menopause symptoms in appropriate
candidates
 Prevention of bone loss
− Hormone therapy has been shown in double-
blind RCTs to prevent bone loss, and in the
WHI, to reduce fractures in postmenopausal
women
9
The Journal of The North American Menopause Society 2017

10. MHT indications
10
The Journal of The North American Menopause Society 2017
 Premature hypoestrogenism
HT is approved for women with hypogonadism, POI,
or premature surgical menopause without
contraindications, with health benefits for
menopause symptoms, prevention of bone loss,
cognition and mood issues, and in observational
studies, heart disease
 Genitourinary symptoms
Hormone therapy has been shown in RCTs to
effectively treat symptoms of vulvovaginal atrophy

11. MHT contraindications
 Current, past or suspected breast cancer,
 Known or suspected estrogen-dependent malignant tumors (e.g. endometrial
cancer),
 Undiagnosed genital bleeding,
 Untreated endometrial hyperplasia,
 Previous idiopathic or current venous thromboembolism (deep venous
thrombosis, pulmonary embolism),
 Active or recent arterial thromboembolic disease (e.g. angina, myocardial
infarction),
 Untreated hypertension,
 Active liver disease,
 Known hypersensitivity to the active substances or to any of the excipients,
 Porphyria cutanea tarda (an absolute contraindication).
The Journal of The North American Menopause Society 2017

12. Main risk factors for MHT use
 Older age (>60 years)
 Obesity (BMI > 30 kg/m2),
 Insulin resistance
 Increase cardiovascular risk (dyslipidaemia,
hypertension, diabetes mellitus, smoking)
 Personal or family history of venous
thromboembolism (VTE)
The presence of risk factors does not necessarily preclude use of MHT
Women’s Health 2019

13. Recommendations for use of hormone
therapy in symptomatic menopausal
women with risk factors*
*Note: Based on international guidelines, clinical literature and expert opinion (clinical experience and
expertise) of the authors
Minerva Ginecol 2018; 70(1): 27–34
Diabetes Res 2015; 2015: 916585
Endocr Pract 2017; 23(7): 869–880

14. Age >60 years or more than 10 years since onset of menopause
 For current users of MHT it can be continued at an appropriate dose (lowest
effective dose) for an appropriate time if no new contraindications emerge
 For new users in whom MHT is indicated, and in the absence of major
contraindications, treatment with transdermal oestradiol (either 25 mcg patch
or gel, 1 puff per day) and vaginal progesterone (either 100 mg in the evening
continuously or 200 mg in the evening for 14 days a month) is preferred. If
other risk factors are present, vaginal treatment with oestradiol or oestriol is
preferred

15. Obesity (BMI > 30 mg/m2)
 As elevated oestrone production from adipose tissue increases the risk of
proliferative endometrial lesions, protecting the endometrium with
progesterone or progestogens (e.g. levonorgestrel or dienogest intrauterine
system) is a priority.
 The woman’s willingness to make lifestyle improvements should be
empowered.
J Steroid Biochem Mol Biol 2007; 106(1–5): 81–96

16. Insulin resistance
 Menopausal HT should be recommended to
women with type 2 diabetes, or a family history
of diabetes, as it reduces progression
Diabetes Res 2015; 2015: 916585
Climacteric 2014; 17(5): 540–556

17. Hypertension
 Menopausal HT can improve recent-onset
hypertension, with enhanced response to
antihypertensive drugs
 the option to start transdermal HT should
be discussed with a cardiologist

18. Smoking
 Women who smoke should be counselled to
quit while also increasing daily aerobic exercise
in order to improve endothelial function, reduce
hypertension and, if relevant, reduce the risk of
weight gain
 For women who choose not to quit, vaginal HT
is preferred. In selected cases, systemic HT
may be considered, but only if the woman is
fully aware of the higher independent
cardiovascular risk due to smoking

19. Dyslipidemia
 Transdermal MHT is preferred in women with dyslipidemia

20. Venous thromboembolism: personal or familial
 Vaginal HT with oestradiol or oestriol is preferred

21. Step 2
Hormonal therapy options

22. Basics of MHT
● Estrogen replacement therapy: for
women without a uterus
● Estrogen–progestogen therapy: For
women with intact uterus

23. Oestrogen
● Oestrogen is the primary active component of HT and is the recognized ‘gold
standard’ for treating menopausal symptoms, especially vasomotor
symptoms
● Systemic oestrogens used for MHT in India are conjugated equine estrogens
(CEEs) and oestradiol valerate

24. Estradiol valerate:
● Natural estrogen
● Safer than its synthetic counterpart
● Micronized form: Increased dissolution and bioavailability
● Esterified preventing extensive first pass metabolism in liver and GIT
● Convenient oral administration
● Is safe even for long-term use (adherence is good even after 7 yrs. of
therapy)*
*Peter HM. Long term adherence to continuous combined HRT. Seven-year update on the Heikkinen
study. Menopause international. 2003;9:8-9

25. Parameters Estradiol Valerate Conjugated Estrogens (CE) Comments
Source Natural Pregnant mare’s urine
product
Estrogenic activity Estradiol valerate
contains the most active
estrogen i.e 17-
estradiol.
CE contains 52 –61% of
estrone that is 1/3 of Estradiol
activity.
CE also contains unknown
ingredients.
Ten hormones present in CE are chemically
different from female hormones.
Unknown ingredients may cause any
possible adverse effect.
Mammographic
density
No significant effect1 Significant increase in
mammographic density 2
Increase in mammographic density may be
a concern as it is a predictor of cancerous
growth in the breasts.
Blood Pressure
(BP)
No effect on renin-
aldosterone system.
Stimulates the liver
production angiotensinogen,
therofore increases BP
CE by stimulating renin-angiotensin
system is associated with the risk of
hypertension.
Coagulation Factor No effect on factor VII  factor VII CE ( by  factor VII) may cause abnormal
increase in clotting of blood.
Medscape Womens Health. 2002 Jul-Aug;7(4):1; Ginecol Obstet Mex. 2000 Nov;68:442-7.
E2V vs Conjugated Equine Estrogens

26. Parameters Estradiol valerate Conjugated estrogen (CE) Comments
Vasomotor
symptoms
Hot flushes, severe throbs, and
breast tenderness is lower 3
Presence of vasomotor
symptoms are higher with CE
EV could be an option that is
better accepted by
postmenopausal women. It is the
drug approved by US FDA for such
condition.
Lipid profile and
cardioprotective
effect
Offers favorable lipid profile4 Lesser favorable lipid profile. EV has better bioavailability and
therefore, is a better option in
dealing with concerns of
postmenopausal cardiovascular
protection
Endothelial function EV improves endothelial
function and reduces plasma
levels of endothelin-15
Vasoprotective effect not
reported
EV has fast effects on endothelial
function thus acutely
vasoprotective
Plasma
homocysteine level
EV has no effect on plasma
homocysteine level6
Effect on homocysteine level
not reported
Homocysteine is a risk factor for
CHD. EV reduces the risk of CHD
3Maturitas. 1997 Jul;27(3):275-84.
4Maturitas. 2001 Dec 14;40(3):239-45; 5Acta Obstet Gynecol Scand. 2006;85(11):1304-6.
E2V vs Conjugated Equine Estrogens

27. Vaginal Estrogen: Treatment of GSM*
Estrogen Preparation (FDA Approved)
Vaginal creams: 17-beta estradiol, conjugated estrogens
Vaginal ring: 17-beta estradiol, estradiol acetate
Vaginal tablet inserts: Estradiol hemihydrate
CLEVELAND CLINIC JOURNAL OF MEDICINE 2018
*Genitourinary Syndrome of Menopause

28. Vaginal Estrogen: Treatment of GSM*
Local Estrogen & Endometrial Impact
● Endometrial surveillance with either transvaginal ultrasonography or
endometrial sampling is not required, even with long-term use, but it should
be considered with higher doses or more frequent applications
● Progestogen therapy is not recommended with low-dose vaginal ET, but
appropriate evaluation of the endometrium should be performed if vaginal
bleeding occurs, given the limitations of safety data
CLEVELAND CLINIC JOURNAL OF MEDICINE 2018
*Genitourinary Syndrome of Menopause

29. Rationale of Progestogen in MHT
● Since chronic unopposed exposure of the endometrium to oestrogen
increases the risk of endometrial hyperplasia and cancer, progestogens are a
part of systemic HT in menopausal women with an intact uterus

30. Selecting the ‘Best’ Progestogen
● Although selecting the ‘best’ progestogen for use in an individual patient
requires further clarification, there is evidence to suggest that micronized
progesterone have better risk profiles than medroxyprogesterone acetate
(MPA), and is associated with a lower risk of breast cancer compared with
other progestogens
Maturitas 2014; 77(4): 311–317

31. Progestogens available for MHT
Characteristic Androgenic Non-androgenic
Norethisterone acetate Levonorgestrel MPA Dydrogesterone
Micronised progesterone
Route of administration
Oral
Transdermal
Oral
Transdermal
Intrauterine
Oral
Oral
Oral

32. An international expert panel’s recommendations on MHT containing micronized
progesterone are as follows
○ Oral micronized progesterone provides endometrial protection if applied
sequentially for 12–14 days/month at 200mg/day for up to 5 years
○ Vaginal micronized progesterone may provide endometrial protection if applied
sequentially for at least 10 days/month at 4% (45 mg/day) or every other day at
100mg/day for up to 3–5 years (off-label use)
○ Transdermal micronized progesterone does not provide
endometrial protection
32
CLIMACTERIC, 2016
Selecting the ‘Best’ Progestogen

33. Dydrogesterone
● According to the Women's Health Initiative (WHI) study, the most important
risks during combined hormone replacement therapy (HRT) are breast
cancer, stroke and venous thromboembolism.
● To date, combinations of estradiol with natural progesterone or its
retroisomer dydrogesterone are the only combined HRT regimens for which
large case–control or cohort studies show no increase in any of these three
risks.
● Moreover, due to the neutral effect of dydrogesterone on the vascular and
metabolic systems, the preventive effect of the estradiol component with
respect to myocardial infarction and metabolic syndrome can be maintained if
HRT is started early after the menopause.
Alfred O. Mueck, Harald Seeger, Kai-J. Bühling,Use of dydrogesterone in hormone replacement therapy, Maturitas,
Volume 65, Supplement 1,2009,Pages S51-S60,ISSN 0378-5122,https://doi.org/10.1016/j.maturitas.2009.09.013.

34. Dydrogesterone
● Although a study with the same design as the WHI has not been performed,
these results appear to be plausible considering the positive experimental
evidence, particularly in the context of breast cancer and cardiovascular
risks/benefits.
● Combination with dydrogesterone avoids endometrial hyperproliferation,
maintains the beneficial effects of estradiol (i.e. efficacy against climacteric
symptoms and prevention of osteoporotic fractures) and minimizes the most
important risks known to be associated with the progestogen components of
HRT regimens.
● More studies needed to know the safety of this drug in MHT.
Alfred O. Mueck, Harald Seeger, Kai-J. Bühling,Use of dydrogesterone in hormone replacement therapy, Maturitas,
Volume 65, Supplement 1,2009,Pages S51-S60,ISSN 0378-5122,https://doi.org/10.1016/j.maturitas.2009.09.013.

35. Different routes MHT
 Transdermal – patch, gel
 Oral
 Vaginal

36. Dose and route of administration
 Most appropriate dose of HT depends on the woman’s
phase of life, age and general health status
 Useful approach may be to start HT at a low dose, then
titrate upwards to the lowest effective dose that is
consistent with the woman’s treatment goals
Women’s Health 2019

37. Step 3
Starting MHT treatment

38. Starting MHT
 International guidelines recommend that HT be
started as soon as menopausal signs or symptoms
appear which, in most women, is between 45 and
55 years of age
 Women with primary ovarian insufficiency require
earlier and continued use of HT (at least until the
normal age of menopause) to protect against
associated postmenopausal chronic diseases
Women’s Health 2019;15:1-8

39. Starting MHT
Evaluating risk factors for MHT in candidate patients
Questions to ask
 Age
 Menstruation status
 Menopausal symptoms
 Past and current medical history
 Family history
 Lifestyle factors (e.g. smoking, alcohol use, exercise)
 Concurrent medications
Women’s Health 2019;15:1-8

40. Evaluating risk factors for MHT in candidate patients
Examinations/investigations to perform:
 Body weight
 Waist circumference
 Blood pressure
 Blood tests if indicated by responses to questioning
 Imaging (e.g. ultrasound, bone density) if indicated by responses to
questioning
 Mammography if not performed within previous year
 Bone densitometry (dual-energy x-ray absorptiometry)
if patient at risk for osteoporosis
Women’s Health 2019;15:1-8
Starting MHT

41. A Practical Approach
Uterus intact Post hysterectomy
First line
management
A. Oral E
B. Transdermal E patch or gel
A. Oral E plus oral P
B. Combined transdermal (E+P) patch
Jane and Davis; A practitioner’s Toolkit for the Menopause; Jean Hailes for Women’s Health | jeanhailes.org.au

42. Cyclical/sequential HT
 Cyclical or sequential HT involves daily administration of oestrogen, with the
addition of progestogen for 10– 14 days a month (monthly bleeds) or for 10–
14 days every 13 weeks (bleeds every 3 months)
 Any irregular bleeding and/ or spotting that occurs in addition to regular
progestogen withdrawal bleeds can be managed by increasing the oestrogen
dose as this stabilizes the endometrium
Climacteric 2016; 19(4): 316–328

43. Continuous HT
 this regimen eliminates withdrawal bleeding and promotes amenorrhea
 Should be used only in women who are at least 2 years past their last
menstrual period as it can cause irregular bleeding in perimenopausal women
due to the unpredictable residual production of oestradiol by remaining
primordial ovarian follicles
Climacteric 2016; 19(4): 316–328

44. Step 4
Follow-up

45. Follow-up of patients prescribed MHT
 Schedule a follow-up appointment after
initiation of a MHT regimen in one month, to
assess treatment effect
 Adverse effects of MHT include bloating,
breast tenderness, increased blood pressure,
headaches, fluid retention and urinary
incontinence
www.bpac.org.nz

46. Follow-up of patients prescribed MHT
What to do if there is persistent vasomotor
symptoms?
 Increase MHT doses or try another
formulation
www.bpac.org.nz

47. Follow-up of patients prescribed MHT
What to do if there is breast tenderness ?
 Reduce the dose of oestrogen or switch to
another progestogen
www.bpac.org.nz

48. Follow-up of patients prescribed MHT
What to do if there is unscheduled bleeding within the first three months ?
Consider continuing treatment unless there is a high suspicion of endometrial
cancer as bleeding may settle with time
Other options include:
o Switching to cyclical progestogen for patients taking continuous progestogen
o Increasing the dose of progestogen
o Switching from oral progestogen to a levonorgestrel IUD
www.bpac.org.nz

49. Follow-up of patients prescribed MHT
What to do if there is unscheduled bleeding
after the first three to six months of MHT?
 Organise further investigations for
endometrial cancer
 If no endometrial pathology is detected,
consider increasing oestrogen dose
www.bpac.org.nz

50. Step 5
Stopping Treatment

51. Stopping HT
 Current users of HT can remain on treatment
indefinitely (lifelong if indicated), or at least until
such time as the patient asks to stop
 Regular monitoring of HT is advised, with
adjustments made to type, dosage and/ or route of
administration according to a patient’s changing
circumstances and treatment goals
Women’s Health 2019;15:1-8

52. Key Take Aways
● MHT is a dominant therapeutic modality in Menopausal medicine
● The skill lies in the ability to choose the optimal MHT preparation for the
given patient
● Follow the steps when it is decided to start MHT.
● The key is individualization, minimum possible effective dose, early start of
therapy, adequate follow up

53. My World of sharing happiness!
Shrikhande Fertility Clinic
Ph- 91 8805577600
shrikhandedrlaxmi@gmail.com

54. Questions

55. Proprietary and confidential — do not distribute
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