Menopausal 

hormone therapy – From

Evidence to Practice 
Disclaimer
Disclaimer

For the use only of a Registered Medical Practitioners or Hospital or Laboratory

The Content in this presentation is only intended for healthcare professionals in India. The medical information in this

presentation is provided as an information resource only, and is not to be used or relied on for any diagnostic or

treatment purpose. The views and opinions mentioned in the presentation is strictly that of the author and the

individuals expressing the same and Pfizer may not necessarily endorse the same. Pfizer (including its parent,

subsidiary and affiliate entities) makes no representation or warranties of any kind, expressed or implied; as to the

content used in the presentation and/or the accuracy, completeness of its content  Pfizer India does not promote or

support use of medications manufactured by it in off label indications For specific information regarding various

therapeutic agents, including Pfizer products, please refer to the approved full prescribing information

PP-PEM-IND-0154, 3rd April 2023 See summary of prescribing information on last page

• Pfizer Limited, The Capital- A Wing, 1802, 18th Floor, Plot No. C-70, G Block, Bandra - Kurla
Complex, Bandra (East), Mumbai 400 051, India 

Full prescribing information available on request

 Menopause: Burden

Changes during menopausal transition

Estrogen loss and manifestations of health risks

Menopausal hormone
therapy – From MHT during menopausal transition
evidence to practice 
Estrogen, a gold standard for menopausal symptoms1

Conjugated equine estrogens

Guideline recommendations

Reference
1. Palacios S, Stevenson JC, Schaudig K, et al. Hormone therapy for first-line management of menopausal symptoms: Practical recommendations. Womens Health (Lond). Jan-Dec 2019;15:1745506519864009.
doi: 10.1177/1745506519864009.
Menopause: A rising concern due to increasing life
expectancy1

Menopausal signs and symptoms4

• affect about 80% of women
• By 2030, global population of postmenopausal • 20% of them severely
women will reach 1.2 billion 1
• Indian women could spend 30 years in post-
menopausal stage of life2
• Prioritizing women’s health and QoL is becoming 20%
crucial3 80%

QoL, quality of life

1. Ilankoon IMPS, Samarasinghe K, Elgan. Menopause is a natural stage of aging: a qualitative study. BMC Womens Health. 2021 Feb 1;21(1):47. 2. Pallikadavath S, Ogollah R, Singh A, et al. Natural menopause among women below 50 years in India: A population-based
study. Indian J Med Res. 2016 Sep;144(3):366-377. 3. Lee SR, Cho MK, Cho YJ. Academic Committee of the Korean Society of Menopause. J Menopausal Med. 2020;26(2):69-98. 4. Palacios S, Stevenson JC, Schaudig K, et al. Hormone therapy for first-line management
of menopausal symptoms:Practical recommendations. Womens Health (Lond) . Jan-Dec 2019;15:1745506519864009. doi: 10.1177/1745506519864009.
 Changes in symptoms and mental health1
Events during menopausal transition
Mid life aging (40-65 years)
• Depression and anxiety (transient)
• Urinary incontinence
• Cognitive performance

Menopausal transition
• Vasomotor symptoms (Hot flashes and night sweats) (transient)
• Sleep complaints
• Cognitive difficulties (transient)
• Vaginal dryness
• Sexual pain and sexual desire

SWAN, Study of Women's Health Across the Nation

1. Khoudary Samar R EI, Greendale G, Crawford SL, et al. The menopause transition and women's health at midlife: a progress report from the Study of Women's Health Across the Nation (SWAN). Menopause. 2019 Oct;26(10):1213-1227.
 Changes in physiological systems and functions1

Body mass index and blood pressure

Physical performance (transient)

Lipids, vascular remodelling

Metabolic syndrome

Bone mineral density

Lean mass

Fat mass

SWAN, Study of Women's Health Across the Nation

Changes due to mid life aging (40 – 65 yrs)
1. Khoudary Samar R EI, Greendale G, Crawford SL, et al. The menopause transition and women's health at midlife: a progress report from the
Study of Women's Health Across the Nation (SWAN). Menopause. 2019 Oct;26(10):1213-1227. Changes due to menopausal transition
Estrogen loss and manifestations of health risks

The strongest symptoms of

menopause occur during the
largest drop in hormone levels.1

Adapted from: Bharti J, Choudhary P. Menopause-transition journey in a woman's life from being fertile to infertile: a brief note.
IJRD. 2021;6(9):169-74.

1. Bharti J, Choudhary P. Menopause-transition journey in a woman's life from being fertile to infertile: a brief note. IJRD. 2021;6(9):169-74
Vasomotor symptoms (VMS): Hallmark of menopause1

• Hot flushes
• Anxiety
VMS*2 • Shivering
• Palpitation
• Night sweat

Appear within 1–2

Last for up to 10 Associated with poor May require medical
years from the last
minutes3 QoL2 attention3
day of menstruation2

* Symptom duration greatly varies

1. Khoudary Samar R EI, Greendale G, Crawford SL, et al. The menopause transition and women's health at midlife: a progress report from the Study of Women's Health Across the Nation (SWAN). Menopause. 2019 Oct;26(10):1213-1227. 2. Lee SR, Cho MK, Cho YJ, et al. The 2020
Menopausal Hormone Therapy Guidelines. J Menopausal Med. 2020;26(2):69-98. 3. Abdi F, Mobedi H, Mosaffa N, Dolatian M, Ramezani Tehrani F. Hormone Therapy for Relieving Postmenopausal Vasomotor Symptoms: A Systematic Review. Arch Iran Med. 2016; 19(2): 141 – 146.
VMS associated with CVD events

increased risk of future CVD events

50% to 77% in women with frequent or >2-fold higher risk of CVD events in
persistent VMS women with frequent VMS (≥6 days/2
weeks) Vs women without VMS

Figure: CVD event rate in patients with vasomotor symptoms (VMS). N=3083, 231 events.

Adapted from: Thurston R, Aslanidou Vlachos HE, Derby CA, et al. Menopausal Vasomotor Symptoms and Risk
of Incident Cardiovascular Disease Events in SWAN. J Am Heart Assoc. 2021;10(3):e017416. doi:
10.1161/JAHA.120.017416

CVD, cardiovascular events; SWAN, Study of Women's Health Across the Nation; VMS, Vasomotor symptoms.
1. Thurston R, Aslanidou Vlachos HE, Derby CA, et al. Menopausal Vasomotor Symptoms and Risk of Incident Cardiovascular Disease Events in SWAN. J Am Heart Assoc. 2021;10(3):e017416. doi: 10.1161/JAHA.120.017416..
Risk of depression in menopausal transition

VMS

Depressive Depression
symptoms

Hormonal
changes

1. Lee SR, Cho MK, Cho YJ, et al. The 2020 Menopausal Hormone Therapy Guidelines. J Menopausal Med. 2020;26(2):69-98.
 Genitourinary syndrome of menopause (GSM)

Vaginal Sexual Urinary symptoms

Affects Painful
Dryness
up to 84% of urination
postmenopausal women1 Pain due to
Burning decreased Recurrent UTI
sensation lubrication

Urinary
Irritation urgency

1. NAMS Position Statement. The 2020 genitourinary syndrome of menopause position statement of The North American Menopause Society. Menopause. 2020 Sep;27(9):976-992.
 GSM: Underdiagnosed & undertreated health concern1

Increase in vaginal symptoms2 Significantly impairs1

usal
45
no pa
e
o s sm Health
s a cr n
ne s sitio 34%
y ran
30 na l dr t Sexual
g i
Va function
%increase

19%

15

Quality
of life
0
Pre and early menopause Postmenopause

GSM, Genitourinary syndrome of menopause

1. NAMS Position Statement . The 2020 genitourinary syndrome of menopause position statement of The North American Menopause Society. Menopause. 2020 Sep;27(9):976-992. 2. Khoudary Samar R EI, Greendale G, Crawford SL, et al. The menopause transition and women's
health at midlife: a progress report from the Study of Women's Health Across the Nation (SWAN). Menopause. 2019 Oct;26(10):1213-1227.
 Requires To normalize the
Chronically
GSM progresses1
long-term
treatment1
physiological
environment of the
urogenital organs1

GSM, Genitourinary syndrome of menopause

1. Lee SR, Cho MK, Cho YJ, et al. The 2020 Menopausal Hormone Therapy Guidelines. J Menopausal Med. 2020 Aug;26(2):69-98.
Major health risks of low estrogen1

Heart
Osteoporosis
disease

1. University of Rochester Medical Center. Low Estrogen Levels in Menopause. [Internet] [Cited 22 September 2021] Available from: https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=85&ContentID=P00559.
Osteoporosis

Affects 1 in 10 women# worldwide1

Primarily caused by postmenopausal bone loss due

to estrogen deficiency2
NORA trial on ambulatory postmenopausal
women (n = 200160)3

• ̴50% had undetected low BMD

• 7% of which had osteoporosis
• 4X higher fracture rate in osteoporotic patients*

1. Hormone Health Network. Postmenopause and osteoporosis. [Internet] [Cited 26 Sep 2021] Available from: https://www.hormone.org/diseases-and-conditions/menopause/post-menopause-and-osteoporosis. 2. Management of osteoporosis in postmenopausal women: the
2021 position statement of The North American Menopause Society. Menopause. 2021 Sep 1;28(9):973-997. 3. Siris ES, Miller PD, Barrett-Connor E, et al. Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from
the National Osteoporosis Risk Assessment. JAMA. 2001;286(22):2815-22. *as compared to women with normal BMD; #over the age of 60. BMD, Bone mineral Density; NORA, National Osteoporosis Risk Assessment.
Estrogen regulates bone turnover

Figure adapted from: Tulay Okman-Kilic. Estrogen Deficiency and Osteoporosis. [Published 4th March 2015] [Cited 25 September 2020] Available from: https://www.intechopen.com/chapters/48016

RANK, Receptor activator of nuclear factor kappa-B ligand;

1. Tulay Okman-Kilic. Estrogen Deficiency and Osteoporosis. [Published 4th March 2015] [Cited 25 September 2020] Available from: https://www.intechopen.com/chapters/48016
 Low estrogen during menopausal transition1,2

Bone resorption due

to increased

Osteoblastic NF-
κB activity

Osteoblast
Average reduction
Bone formation apoptosis 10% in BMD2
Oxidative stress

Estrogen deficiency linked with imbalance between

bone resorption and formation
1. Tulay Okman-Kilic. Estrogen Deficiency and Osteoporosis. [Published 4th March 2015] [Cited 25 September 2020] Available from: https://www.intechopen.com/chapters/48016. 2. M.-X. Ji, Q. Yu. Primary osteoporosis in postmenopausal women. Chronic Dis Transl Med.
2015 Mar 21;1(1):9-13.
Heart Disease

Estrogen mediates cardioprotective actions by

Increasing
• After menopause, the risk for heart
disease increases1
Angiogenesis ROS
• Estrogen protects women against
Vasodilation Oxidative stress

Decreasing
heart disease1
Fibrosis

Limits cardiac remodeling

Attenuates heart hypertrophy 
ROS, reactive oxygen species
1. Lorga A, Cunningham CM, Moazeni S, et al. The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy. Biol Sex Differ. 2017 Oct 24;8(1):33.
Menopausal Hormonal Therapy: A validated therapeutic
strategy1

Widely used to treat signs &

symptoms of menopause
Hormonal therapy
Promotes longevity encompasses
• Estrogens
• Progestogens
• Estrogen & progestogen combinations
• Tibolone
• Raloxifene
• Conjugated estrogen and bazedoxifene
combination

1. Palacios S, Stevenson JC, Schaudig K, et al. Hormone therapy for first-line management of menopausal symptoms: Practical recommendations. Womens Health (Lond). Jan-Dec 2019;15:1745506519864009. doi: 10.1177/1745506519864009.
 Approved by FDA for VMS and vulvovaginal atrophy1

Improves Mood, cognitive function and sleep2,3

MHT Prevents osteoporosis and heart disease2

Enhances menopause-specific QoL and global QoL2

FDA, Food and Drug administration; MHT, menopause hormone therapy; QoL, Quality of Life; VMS, Vasomotor symptoms
1. Dwyer JB, Aftab A, Radhakrishnan R, et al. Hormonal Treatments for Major Depressive Disorder: State of the Art. AmJPsychiatry2020;177:686–705. 2. Lee SR, Cho MK, Cho YJ. Academic Committee of the Korean Society of Menopause. J Menopausal Med.
2020;26(2):69-98. 3. Fait T. Menopause hormone therapy: latest developments and clinical practice. Drugs Context. 2019 Jan 2;8:212551. Menopausal hormonal therapy (MHT)
Hormonal therapy for prevention and treatment of
osteoporosis*1

Prevents MHT, in women without osteoporosis,

menopause-related bone loss reduces fractures of1
• Femur
Reduces • Vertebral
risk of fracture
• Non-vertebral

Necessary in women with premature ovarian insufficiency to prevent bone loss 1

MHT, menopause hormone therapy

*menopausal women aged <60 years or those with <10 years since menopause.
1. Lee SR, Cho MK, Cho YJ. Academic Committee of the Korean Society of Menopause. J Menopausal Med. 2020;26(2):69-98.
Estrogen therapy: Gold standard for treating menopausal
symptoms1
Estrogen therapy reduces
frequency and severity of VMS 2
100
80% decrease3
• Hot flushes
75% • Night sweats
87%

Peak effect3
• 4 weeks of treatment

0
Frequency Severity

1. Palacios S, Stevenson JC, Schaudig K, et al. Hormone therapy for first-line management of menopausal symptoms: Practical recommendations. Womens Health (Lond). Jan-Dec 2019;15:1745506519864009. doi: 10.1177/1745506519864009. 2. Fait T. Menopause
hormone therapy: latest developments and clinical practice. Drugs Context. 2019 Jan 2;8:212551. 3. Reid RL, Magee BA. Confronting the challenges of the menopausal transition. Womens Midlife Health. 2015 Oct 5;1:7.
Estrogen for menopausal symptoms1

Effective
in treating severe vaginal atrophy

Recover
normal vaginal flora Estrogens used for Hormone
therapy2
Increases • Conjugated equine estrogens (CEEs)
vaginal discharge • Synthetic conjugated estrogens
• Micronized 17β-oestradiol
Improves • Oestriol
maturation index of the vaginal epithelium • Oestradiol valerate
• Oestradiol hemihydrate

1. Lee SR, Cho MK, Cho YJ. Academic Committee of the Korean Society of Menopause. J Menopausal Med. 2020;26(2):69-98. 2. Palacios S, Stevenson JC, Schaudig K, et al. Hormone therapy for first-line management of menopausal symptoms: Practical
recommendations. Womens Health (Lond). Jan-Dec 2019;15:1745506519864009. doi: 10.1177/1745506519864009.
 Estrogen for menopausal transition

Estrogen therapy1
During • Potentially alleviates symptoms of depression*
• Positive effect on mood disorder#
Menopausal • Prevents cognitive decline

transition* Estrogen in combination with SSRI1

• Improves depression

SSRI, Selective Serotonin Reuptake Inhibitor

1. Lee SR, Cho MK, Cho YJ. Academic Committee of the Korean Society of Menopause. J Menopausal Med. 2020;26(2):69-98.
*in women with depression
#reported in women with surgical menopause
Non-estrogen usage and increased risk of mortality

A study examined
the effect of • Over a 10-year span, a minimum of
estrogen avoidance ET reduces total
18,601 and as many as 91,610
on mortality mortality primarily by
postmenopausal women died
among reducing CHD-related
prematurely due to estrogen
hysterectomized deaths
avoidance.
women aged 50 to
59 years 

CHD, Coronary heart disease; ET, Estrogen therapy

1. Sarrel PM, Valentine YN, Vinante V, et al. The Mortality Toll of Estrogen Avoidance: An Analysis of Excess Deaths Among Hysterectomized Women Aged 50 to 59 Years. Am J Public Health.2013;103(9):1583-8. .
Conjugated equine estrogens (CEE): A preferred estrogen
formulation1

Natural formulation
an extract prepared from pregnant mares’ urine

Manages
early menopausal symptoms

Prevents
osteoporosis, in some cases CVD and AD

Used
either alone or in combination with progestin

AD, Alzheimer's disease; CVD, cardiovascular disease

1. Bhavnani BR, Stanczyk FZ. Pharmacology of conjugated equine estrogens: efficacy, safety and mechanism of action. J Steroid Biochem Mol Biol. 2014 Jul;142:16-29.
 CEE composition
Estrone sulfate

Equilin sulfate

17α-Dihydroequilin sulfate

Equilenin

Comprised of more than 10 17α-Estradiol sulfate

different forms of estrogen
the main components are1 17α-Dihydroequilenin sulfate

17-beta-Dihydroequilin sulfate

Only a minimal amount of 17-beta

estradiol

CEE contains estrone sulfate (a weaker form of estrogen compared to estradiol), as the primary form of estrogen, and
lowest level of E2.2
E2, estradiol
1. Araujo PX, Costa TJ, Echem C, et al. Treatment with Standard and Low Dose of Conjugated Equine Estrogen Differentially Modulates Estrogen Receptor Expression and Response to Angiotensin II in Mesenteric Venular Bed of Surgically Postmenopausal Hypertensive Rats. J Pharmacol
Exp Ther. 2017 Jul;362(1):98-107. | 2. Hiroi R, Weyrich G, Koebele SV, et al. Benefits of Hormone Therapy Estrogens Depend on Estrogen Type: 17β-Estradiol and Conjugated Equine Estrogens Have Differential Effects on Cognitive, Anxiety-Like, and Depressive-Like Behaviors and Increase
Tryptophan Hydroxylase-2 mRNA Levels in Dorsal Raphe Nucleus Subregions. Front Neurosci . 2016 Dec 8;10:517.
 CEE alone or in combination with MPA improved VMS and
vaginal atrophy
Women’s HOPE (Health, Osteoporosis, Progestin, Estrogen) study on 2,673 postmenopausal women (age 40 to 65 years) with an intact uterus.1
Statistically significant decrease in Significant increase in superficial cells
mean number of hot flushes with CEE at cycles 6 and 13 with CEE

(P<.001)
(P<.01)

*Difference from placebo (P<.05) from weeks 2 through 12. †Difference from
placebo (P<.05) from weeks 3 through 12.‡Difference between CEE 0.45 (P<.05) at
weeks 3, 4, 5 and 9. §Difference between CEE 0.625 and CEE 0.45 (P<.05) from
weeks 2 through 12. IIDifference between CEE 0.625 and CEE 0.3 was significant
(P<.05) at weeks 4, 5, 6, 9, 10, and 12.
For each treatment group, the box shows the distance between the 75th and 25th
percentiles, with the median marked as a line, and the “whiskers” show the
maximum (top) and minimum (bottom) values. *Significantly different from CEE
0.625, P<.001. †Significantly different from CEE 0.625.

Adapted from: Fertil Steril. 2001;75(6):1065-79. Adapted from: Fertil Steril. 2001;75(6):1065-79.

CEE, Conjugated equine estrogens; MPA, Medroprogesterone acetate

1. Utian WH, Shoupe D, Bachmann G, et al. Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Fertil Steril. 2001;75(6):1065-79.
CEE + MPA improved VMS and vaginal atrophy

Statistically significant decrease in mean Significant increase in superficial cells

number of hot flushes with CEE/MPA at cycles 6 and 13 with CEE/MPA

(P<.05)
(P<.05)

All values were significant except CEE 0.3/MPA 1.5. *Difference from placebo (P<.05) from
For each treatment group, the box shows the distance between the 75th and 25th
weeks 2 through 12. †Difference from placebo (P<.05) from weeks 3 through 12.‡Difference
percentiles, with the median marked as a line, and the “whiskers” show the maximum
between CEE 0.45/MPA 2.5 (P<.05) at weeks 3, 4, 5 and 9.
(top) and minimum (bottom) values. †Significantly different from CEE 0.625, P<.05.
Adapted from: Fertil Steril. 2001;75(6):1065-79. ‡Significantly different from CEE 0.3/MPA 1.5, P<.05.

Adapted from: Fertil Steril. 2001;75(6):1065-79.

CEE, Conjugated equine estrogens; MPA, Medroprogesterone acetate

1. Utian WH, Shoupe D, Bachmann G, et al. Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Fertil Steril. 2001;75(6):1065-79.
 CEE improve BMD in early postmenopausal women1

HOPE trial
reported
significant gains p<0.001 p<0.001
from baseline in
spine BMD

Figure: Spine BMD change from baseline in women treated with CEE alone of CEE in
combination with MPA. (n = 822 Healthy postmenopausal women; age = 40 to 65 years)
Adapted from: Lindsay R, Gallagher JC, Kleerekoper M, et al. Effect of lower doses of conjugated equine estrogens with and
without medroxyprogesterone acetate on bone in early postmenopausal women. JAMA. 2002;287(20):2668-76.

BMD, Bone mineral density; CEE, Conjugated equine estrogens; MPA, medroxyprogesterone acetate.
1. Lindsay R, Gallagher JC, Kleerekoper M, et al. Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. JAMA. 2002;287(20):2668-76.
CEE prevents the risk of fracture

WHI hormone therapy (HT) trials with extended post-intervention follow up

CEE, 0.625 mg/day + MPA,

2.5 mg/day ̶ women with
intact uterus (n = 16,608)

27, 347 postmenopausal

Statistically significant reduction
women (50-79 years)
in hip fracture (33%, p = 0.03)
compared to placebo1
CEE alone ̶ women with
hysterectomy (n = 10,739)
Favorable benefits in women
with greater time to menopause

CEE, Conjugated equine estrogens; MPA, medroxyprogesterone acetate; WHI, Women’s Health Initiative
1. Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA. 2013 Oct 2;310(13):1353-68.
CEE + progestin improves bone density in early menopausal
women: Clinical evidence

Results from a 2-year, prospective, open-label, randomized-controlled trial including early menopausal women of
age 40 to 60 years
Increase in bone density (%) with CEE +MP or DHG 1

Lumbar
• 2.37% - 0.3mg CEE + 100 mg MP Increased BMD with 0.625 mg CEE + 2.5 mg MPA2
• 4.15% - 0.625 CEE + 10 DHG
Femoral neck • 4.5% Lumbar
• 3.28% - 0.65 CEE + 100 MP • 3.7% Femur
Ward’s Triangle
• 3.77% - 0.65 CEE + 100 MP

Study reported reduced bone turnover rate

Study randomly assigned 123 postmenopausal women to 3 groups: group 1 received 0.625 mg conjugated equine estrogen (CEE) plus 100 mg micronized progesterone (MP), group 2 received 0.3 mg CEE daily plus 100 mg MP, and group 3 received 0.625 mg CEE daily
plus 10 mg dydrogesterone (DHG).
CEE, conjugated equine estrogen; MP, micronized progesterone; DHG, dydrogesterone.
1. Zuo Hongling, Sun A, Gao L, et al. Effect of Menopausal Hormone Therapy on Bone Mineral Density in Chinese Women: A 2-Year, Prospective, Open-Label, Randomized-Controlled Trial. Med Sci Monit. 2019;25:819-826. 2. . Lee SR, Cho MK, Cho
YJ. Academic Committee of the Korean Society of Menopause. J Menopausal Med. 2020;26(2):69-98
Controversies regarding the safety of estrogen1

WHI trial: 5.6-year observation1,2

EPT increases risk of
• CHD in older women (HR 1.18 (95% confidence interval [CI] 0.95–1.45)
• Breast cancer*
• Dementia (in women >65 years),
As per a study
• Gallbladder disease, and by British
• Urinary incontinence Menopausal ET alone did not increase breast
society1 cancer risk

EPT tends to increase the risk

*Risk limited to women with a treatment history of MHT

EPT, estrogen–progestogen therapy; ET, estrogen therapy; WHI, Women's Health Initiative

1. Lee SR, Cho MK, Cho YJ. Academic Committee of the Korean Society of Menopause. J Menopausal Med. 2020;26(2):69-98. | 2. Manson JAE, Chlebowski RT, Stefanick ML, et al. The Women’s Health Initiative Hormone Therapy Trials: Update
and Overview of Health Outcomes During the Intervention and Post-Stopping Phases. JAMA. 2013 Oct 2;310(13):1353-68..
 CEE: With a balanced risks and benefits1

7.2-year observation
treatment with CEE alone2
WHI trial • Reduced risk of breast cancer
• Favorable results for all-cause mortality, myocardial infarction
• Fewer cases of adverse events*

*(per 10,000 women per year) from 19 fewer cases for age 50–59 to 51 excess cases for age 70–79,

CEE, Conjugated equine estrogens; WHI, Women's Health Initiative

1. Manson JoA, Chlebowski RT, Stefanick ML, et al. The Women’s Health Initiative Hormone Therapy Trials: Update and Overview of Health Outcomes During the Intervention and Post-Stopping Phases. JAMA. 2013; 310(13):
1353–1368.
Increased risk of hypertension with CEE alone or in
combination with MPA

Concern Need of the hour

• CEE plus MPA and CEE alone, may increase • Alternate dose, formulation, or route of
the risk of developing hypertension in post- administration for estrogen that may not
menopausal women* detrimentally influence blood pressure

Lower doses of oral CEE (0.45 mg/d) taken with cyclical micronized
progesterone did not increase blood pressure†
CEE, conjugated equine estrogens; MPA, medroxyprogesterone acetate. 

*Outcomes from Women's Health Initiative (WHI) trial and post-interventional follow-up of WHI trial. Trial included 27,347 postmenopausal women aged 50 to 79 years. Women with an intact uterus received CEE (0.625 mg/d) plus MPA (2.5 mg/d) (n =
5994) or placebo (n = 5679). Women with prior hysterectomy received CEE alone (0.625 mg/d) (n = 3108) or placebo (n = 3234) (p=0.04).
†
A four-year randomized trial of 727 younger postmenopausal women, transdermal estradiol or lower doses of oral CEE (0.45 mg/d) taken with cyclical micronized progesterone did not increase blood pressure.
1. Swica Y, Warren MP, Manson JE, et al. Effects of Oral Conjugated Equine Estrogens with or without Medroxyprogesterone Acetate on Incident Hypertension in the Women’s Health Initiative Hormone Therapy Trials. Menopause. 2018;25(7):753-761.
 Micronized progesterone: An alternative to earlier MPA

Micronized progesterone-containing HRT vs MPA-

containing regimen significantly improved (p < 0.001)*1

o Vasomotor symptoms
o Somatic complaints
o Anxiety and depressive symptoms
women reported overall
80% satisfaction with MP containing
HRT regimen

Improved QoL†

HRT, Hormone Replacement Therapy; MP, micronized progesterone; MPA, medroxyprogesterone acetate; QoL, Quality of life
*A cross-sectional survey examined QoL related to physiological, somatic, and vasomotor effects of changing progestogen treatment from MPA to MP in postmenopausal women (n = 176)
†measured by improvement of menopause-associated symptoms
1. Fitzpatrick LA, Pace C, Wiita B. Comparison of regimens containing oral micronized progesterone or medroxyprogesterone acetate on quality of life in postmenopausal women: a cross-sectional survey. J Womens Health Gend Based Med. 2000 May;9(4):381-7.
Guideline Recommendations

Indian Menopause Society (IMS) 2019–20201

North American Menopause Society (NAMS)2
GSM: Correction of deficiency GSM with VMS
• Estriol cream - 0.5mg /day vaginal
application or Tab Estriol 1-8mg/day OD
before a meal OR CEE- 0.3 mg-1.25mg/day • Systemic ET for women with moderate to
of vaginal application for 15 days. severe GSM along with VMS2

American Heart Association

Initiation of MHT3
GSM: Maintenance therapy
• Tab estriol 1mg/daily or estriol cream • Initiation at age <60 years or <10 years
0.5mg or CEE- 0.3 mg- twice weekly for 2 of menopause ̶ reduces CVD risk.
months to 1 year.
GSM, genitourinary syndrome of menopause; VSM, Vasomotor Symptoms; ET, Estrogen.
1. Meeta M, Digumarti L, Agarwal N, et al. Clinical Practice Guidelines on Menopause: *An Executive Summary and Recommendations: Indian Menopause Society 2019–2020. J Midlife Health. 2020; 11(2):55-95. | 2. The 2020 genitourinary syndrome of menopause
position statement of The North American Menopause Society. Menopause. 2020 Sep;27(9):976-992. |3. . El Khoudary SR, Aggarwal B, Beckie TM, et al. Menopause Transition and Cardiovascular Disease Risk: Implications for Timing of Early Prevention: A Scientific
Statement From the American Heart Association. Circulation. 2020 Dec 22;142(25):e506-e532
Menopausal hormone therapy initiation

Recommended
• Age <60 years and
• Menopause onset < 10 years and
• With low risk of breast cancer and CVD

Consider with caution

• Age ≥60 years or
• Menopause onset >10 years prior or
• Moderate risk of breast cancer or CVD

Avoid
• High risk of breast cancer or CVD
• Age ≥60 years or
• Menopause onset >10 years prior and
• Moderate risk of breast cancer or CVD
CVD, cardiovascular disease

1. Shifren JL, Crandall CJ, Manson JE. Menopausal Hormone Therapy. JAMA. 2019;E1-E2.
Conclusion

 Side effects and concerns associated with HT hamper its acceptance in clinical practice.
 MHT offers more advantages than disadvantages for women < 60 years or who have had
menopause < 10 years.
 Understanding the risks and benefits of HT is important to design the management plans.
 CEE is a natural therapy widely used in relieving VMS and preventing osteoporosis and other
health conditions.
 It is effective and less likely to cause breast cancer or uterine cancer.

CEE, Conjugated equine estrogens; HT, Hormone therapy; MHT, Menopausal Hormonal therapy; VMS, Vasomotor symptoms
PREMARIN TABLETS, SUMMARY OF PRESCRIBING INFORMATION. Before prescribing, please refer to the full prescribing information of PREMARIN. Generic name of product: Conjugated estrogens tablet, ®Registered
Proprietor - Wyeth LLC, USA. Licensed User - Pfizer Limited, India. Presentation: Dosage Form: Coated tablet
Strength: 0.3 mg and 0.625 mg, Pack size: 28, Active pharmaceutical ingredient: Each tablet contains 0.3 mg or 0.625 mg of conjugated estrogens. Indication: Treatment of moderate to severe vasomotor symptoms
associated with the menopause.Treatment of vulvar and vaginal atrophy. Prevention of post-menopausal osteoporosis. Prevention of post-menopausal osteoporosis in women at risk of future fractures.
Management of post-menopausal osteoporosis. Management of post-menopausal osteoporosis in women at risk of future fractures. Hypoestrogenism due to hypogonadism, castration, or primary ovarian failure.
Dosage and admiistration: Adults: Conjugated estrogens 0.625-1.25 mg daily is the usual starting dose for women without a uterus. Continuous administration is recommended. For initiation and continuation of
treatment of postmenopausal symptoms, the lowest effective dose for the shortest duration should be used. Patients should be reevaluated periodically to determine if treatment for symptoms is still necessary.
Vasomotor symptoms: 0.625-1.25 mg daily depending on the response of the individual. Atrophic vaginitis, kraurosis vulvae, atrophic urethritis: 0.625-1.25 mg daily depending on the response of the individual.
Prophylaxis of postmenopausal osteoporosis: When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and
non-estrogen medications should be carefully considered. The minimum effective dose is 0.625 mg for most patients. Elderly- There are no special dosage requirements for elderly patients, but as with all
medicines, the lowest
effective dose should be used. Paediatric population- Conjugated estrogens is not recommended for use in children. Conjugated estrogens is not indicated during lactation. Method of administration: Oral.
Contraindications: Hypersensitivity to conjugated estrogen or to any of the excipients, Known, suspected or history of breast cancer, Known or suspected estrogen-dependent malignant tumours (e.g. endometrial
cancer), Undiagnosed genital bleeding, Untreated endometrial hyperplasia, Previous or current venous thromboembolism (deep venous thrombosis, pulmonary embolism), Known thrombophilic disorders (e.g.
protein C, protein S, or antithrombin deficiency), Active or recent arterial thromboembolic disease (e.g., angina, myocardial infarction), Acute liver disease or history of liver disease where the liver function tests
have failed to return to normal, Porphyria. Warnings & Precautions: For the treatment of postmenopausal symptoms, HRT should only be initiated for symptoms that adversely affect the quality of life. In all cases, a
careful appraisal of the risks and benefits should be undertaken at least annually and HRT should only be continued as long as the benefit outweighs the risk. Evidence regarding the risks associated with HRT in the
treatment of premature menopause is limited. Due to the low level of absolute risk in younger women, however, the balance of benefits and risks for these women may be more favourable than in older women. Before
initiating or reinstituting HRT, a complete personal and family medical history should be taken. these conditions may recur or be aggravated during treatment with conjugated estrogens, in particular: Leiomyoma (uterine
fibroids) or endometriosis, risk factors for thromboembolic disorders, risk factors for estrogen dependent tumours (e.g. first degree heredity for breast cancer), Hypertension, Liver disorders (e.g. liver adenoma),
Diabetes mellitus with or without vascular involvement, Cholelithiasis, Migraine or (severe) headaches, Systemic lupus erythematosus (SLE), A history of endometrial hyperplasia, Epilepsy, Asthma, Otosclerosis. In
women with an intact uterus the risk of endometrial hyperplasia and carcinoma is increased when estrogens are administered alone for prolonged periods. Risk of breast cancer, ovarian cancer, VTE, coronary artery
disease, ishchemic stroke. Drug interactions: The metabolism of estrogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 3A4
(CYP3A4) enzymes. Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4, such as St. John's Wort (Hypericum perforatum) preparations, phenobarbital, phenytoin,
carbamazepine, rifampicin, rifabutin, nevirapine, efavirenz and dexamethasone, may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the
uterine bleeding profile. Inhibitors of CYP3A4, such as cimetidine, erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, nelfinavir and grapefruit juice, may increase plasma concentrations of
estrogens and may result in side effects. Laboratory test interactions- Increased platelet count decreased levels of antithrombin III, and increased plasminogen antigen and activity. Estrogens increase thyroid-
binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 levels by column or by radioimmunoassay or T3 levels by radioimmunoassay. T3 resin
uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Other binding proteins may be elevated in serum, i.e., corticosteroid binding globulin (CBG), sex hormone-
binding globulin (SHBG) leading to increased circulating corticosteroid and sex steroids respectively. Free or biologically active hormone concentrations may be decreased. Increased plasma HDL and HDL2
cholesterol subfraction concentrations, reduced LDL cholesterol concentrations, increased triglyceride levels. Impaired glucose tolerance. The response to metyrapone may be reduced. Overdose: Numerous
reports of ingestion of large doses of estrogen containing oral contraceptives by young children indicate that acute serious ill effects do not occur. Overdosage of estrogens may cause nausea and vomiting, and
withdrawal bleedingmay occur in females. There is no specific antidote and further treatment should be symptomatic. Adverse reactions: Breakthrough bleeding/spotting; Breast pain, tenderness, enlargement;
Discharge. Changes in weight (increase or decrease); Increased triglycerides. Arthralgias, Leg cramps, Alopecia, Depression. Pharmaceutical precautions: Store below 30°C. Keep out of reach of children. Shelf
life- 24 months. Pharmacokinetics/Pharmacodynamics: Conjugated estrogens are well-absorbed from the gastrointestinal tract. Maximum plasma concentrations are achieved approximately 6-10 hours following
administration. The estrogens are generally eliminated in near-parallel fashion,with half-lives ranging from 10-20 hours.
SPI of LPDPRM022021