Tissue Selective Estrogen Complex

(TSEC): Does it better than

conventional HRT in menopause?

Kanadi Sumapradja
kanadisuma@yahoo.com

Department of Obstetrics and Gynecology

Today’s objective

Background – Results from WHI study

Hormonal treatment without progestogens

A new SERM

Combining SERM/CE – TSEC

Take home messages

Results from WHI study
 Summary
Estrogen + Progestogen
Cardiovascular risk Increased risk of CVD in the
first year of use, but overall
risk for cardiovascular events
did not reach statistical
significance at 5.2 years of use
Breast cancer Small increased risk of
invasive breast cancer after an
average of 5.2 years of use (RR
1.26)
Stroke Risk of stroke increased by
31%
Venous-thromboembolism Risk of VTE doubled as
compared with placebo
Dementia and cognitive Increase risk of dementia in
impairment women aged 65 years and
above
Who is the bad guy?
Estrogen only
There was no effect on CVD
when E-alone was used for 6.8
years
No increased risk of breast
cancer after an average of 6.8
years of use, and in fact shows
a possible trend towards a
reduction of breast cancer
Risk of stroke increased by
39%
Trend towards an increased
risk, but not statistically
significant
No statistically significant
increased risk of dementia
The role of progestogens in HRT
Progestogens used as agents in combined hormone therapy
(HT) offer only 1 benefit:
They provide essential protection against estrogen-induced
endometrial hyperplasia and cancer in women with a uterus.

Langer RD. J Fam Pract. 2007

Progestin effect to endometrium

CEE 0.625mg/d + MPA 2.5mg/d

CEE 0.625mg/d CEE 0.625mg/d +

MP 200mg/d (12 d per month)
MPA 10mg/d (12 d per month)

PEPI = Post-menopausal Progesterone Estrogen Intervention

Progestin effect to breast
RR/OR of breast cancer: E alone < E+P Seq. < E+P Cont.

Non-
users

Campagnoli C., et al. J Steroid Biochem Mol Biol 2005;96(2):95-108

Progestin effect to cardiovascular system

Komm BS., et al. Pharmaceutical 2012;5: 899-924

 We are going to need hormonal
treatment without progestogens
Selective Estrogen Receptor Modulator
(SERM)
Selective estrogen receptor modulators
(SERMS) are synthetic, non-steroidal
agents that bind to the estrogen
receptor (ER), resulting in estrogen-
agonist or estrogen-antagonist effects of
varying magnitudes in different target
tissues.
Cosman F.
Martinkovich S., et al. CIA 2014;9:1437-52
Riggs BL. Et al. N Engl J Med 2003;348:618-29.
We are going to need a new SERM
Bazedoxifene

Bazedoxifene is a novel, non-steroidal, indole-based SERM currently under development by Wyeth

Pharmaceuticals (Gruber and Gruber 2004). It was developed using raloxifene as a template with
the benzothiophene core substituted by an indole ring
Biskobing DM. CIA 2007;2(3):299-303
Komm BS., et al. Ther Adv Musculoskel Dis 2012;4(1):21–34
Komm BS., et al. Ther Adv Musculoskel Dis 2012;4(1):21–34
Combining all the advantages
 The tissue selective estrogen complex (TSEC)

A combination between SERM with one or more estrogens.

The goal of a SERM/CE pairing is to blend the positive effects of

estrogens on menopausal symptoms and bone with the
protective effects of a SERM on the endometrium and breast in
women with a uterus

A potential TSEC should address include endometrial and breast

protection without counteracting the positive effects of
estrogens on the central nervous system, skeleton, and vagina.

Komm BS., et al. Pharmaceutical 2012;5: 899-924

The tissue selective estrogen complex (TSEC) and
endometrial thickness
The tissue selective estrogen complex (TSEC) and
incidence of amenorrhea
The tissue selective estrogen complex (TSEC) and
incidence of hot flashes (at screening at week 9-12)
The tissue selective estrogen complex (TSEC) and
bone resorption
 Take home messages
Bazedoxifene dose dependently decreased endometrial
thickness when partnered with CE as a TSEC

Incidence of amenorrhea similar to that of placebo- treated

women

Bazedoxifene/CE significantly diminished the number and

severity of hot flashes

Bazedoxifene/CE significantly reduced bone

The best dosage of Bazedoxifene/CE is 20mg/0.625mg

Terima Kasih