ORMELOXIFENE- A New Treatment

Modality in DUB

Dr.Surendra Nath Panda, M.S.

Professor of Obstetrics and Gynaecology.
M.K.C.G.Medical College.
Berhampur, Orissa, INDIA
 Dysfunctional Uterine Bleeding

 MOST COMMON MENSTRUAL DISORDER

 CAN AFFECT ANY WOMEN FROM
MENARCHEE TO MENOPAUSE
 OFTEN THE FIRST CLINICAL DIAGNOSIS FOR
ANY EXCESSIVE MENSTRUAL BLEEDING
 DIAGNISIS HAS TO BE CONFIRMED BY A
PROCESS OF EXCLUSION OF
PATHOLOGICAL CAUSES
 Dysfunctional Uterine Bleeding

 EXACT PATHOPHYSIOLOGY STILL NOT

KNOWN
 BASIS OF EXCESSIVE BLEEDING IS
 MOSTLY AN ENDOCRINE ABNORMALITY:
-OESTROGEN - PROGESTERONE IMBALANCE
(mostly estrogen dominance)
 ALTERED PROSTAGLANDIN SYNTHESIS
INFAVOUR OF E2 THAN E2
 Endocrine Abnormality In DUB

 OVULATUION : - NORMAL

 PHASE CHANGE: - SHORTENED FP

 ENDOMET.
HISTOLOGY: - NORMAL
 MENSTRUAL
PATERN: - POLYMENORRHOEA
MENORHAGIA
 Endocrine Abnormality In DUB

 OVULATUION : - NORMAL

 PHASE CHANGE: - LONG F P

 ENDOMET.
HISTOLOGY: - NORMAL
 MENSTRUAL
PATERN: - OLIGOMENORRHOEA
MENORHAGIA
 Endocrine Abnormality In DUB

 OVULATUION : - ABNORMAL COR.LUT

 PHASE CHANGE: - SHORT L P

 ENDOMET.
HISTOLOGY: - DEFICIENT SEC. END.
 MENSTRUAL
PATERN: - PRE MENS. SPOTTING
MENORHAGIA
 Endocrine Abnormality In DUB

 OVULATUION : - PERSISTENT COR. LUT.

 PHASE CHANGE: - LONG L P

 ENDOMET.
HISTOLOGY: - WELL DEV. SEC. END.
 MENSTRUAL
PATERN: -
PROLONGED CYCLES
 Endocrine Abnormality In DUB

 OVULATUION : - ANOVULATION
(Insufficient follicles)
 PHASE CHANGE: - SHORT CYCLES
 ENDOMET.
HISTOLOGY: - DEFICIENT PRO. END.
 MENSTRUAL
PATERN: - POLYMENORRHAGIA
MENORRHAGIA
 Endocrine Abnormality In DUB

 OVULATUION : - ANOVULATION
(Polycystic Ovaries)
 PHASE CHANGE: - PROL. CYCLES
 ENDOMET.
HISTOLOGY: - PRO. / HYPERPLASTIC
 MENSTRUAL
PATERN: - OLIGOMENORRHOEA
METROPATHIA
HAEMORRHAGICA
 Endocrine Abnormality In DUB
OVULATION PHASE END. HIST MENSTRUAL
CHANGE PATERN

NORMAL SHORTENED F P NORMAL POLYMENORRHAGIA

MENORRHAGIA
NORMAL LONG F P NORMAL OLIGOMENORRHOEA
MENORRHAGIA

ABNORMAL SHORT L P DEFICIENT PRE MENS. SPOTTING

COR.LUT SEC. END. MENORHAGIA

PERSISTENT WELL DEV. SEC. PROLONGED CYCLES

LONG L P
COR. LUT END
ANOVULATION SHORT CYCLES DEFICIENT POLYMENORRHAGIA
(Insufficient follicles) MENORRHAGIA
PRO. END.

PROL. CYCLES PRO. / OLIGOMENORRHOEA

ANOVULATION
(Polycystic HYPERPLASTIC METROPATHIA
Ovaries) HAEMORRHAGICA
 D U B - Management Options

CONSERVATIVE     D & C     MEDICAL

  
SPONTANEOUS CURE   
  
RECURENCE     D & C   FAILURE /
 RECURENCE
  
  
-SURGERY-
ENDOMETRIAL ABLATION / HYSTERCTOMY
 Medical Treatment for DUB

 HORMONES  SECOND LINE &

mostly Adjuvant
 Es+Pr
NSAIDs
 Progestogens Mefenamic acid
 Estrogen Ethamsylate
Antifibrinolytics
 Androgens + • EACA
Estrogen • Tranexamic
 Danazol acid
Radiotherapy ?
 GnRha
 Medical Treatment for DUB
Problems: -
 Treatment has to be indivisualised
 Not suitable for all ages
 Response is erratic and unpredictable
 SIDE EFFECTS - Discontinuation and
noncompliance
 Failures are common
 Cost effectiveness ?
 Surgery is often resorted to
 Surgical Treatment of DUB
ENDOMETRIAL ABLATION: -

 HYSTEROSCOPIC METHODS: -

• TCRE – Tran Cervical Resection Of

Endometrium
• ELA – Endrometrial Laser Ablation
• HTEA – Hydrothermal Endrometrial Ablation
 Surgical Treatment of DUB
ENDOMETRIAL ABLATION: -
 NON HYSTREOSCOPIC METHODS: -
• RFEA – Radio Frequency Endometrial Ablation
• TBEA – Thermal Balloon Endometrial Ablation
• VSEA – Vestablate System Endometrial Ablation
• MWEA – Microwave Endometrial Ablation
• ERA – Endometrial Resection and Ablation With a
Specialised Tissue Aspiration Resectoscope (STAR)
• TUMA – Total Uterine Mucosa Ablation by a Calibrated
Uterine Resection Tool (CURT)
 Surgical Treatment of DUB

HYSTERCTOMY: -

• VAGINAL HYSTERECTOMY
• LPAROSCOPICALLY ASSISTED V H
• Lap Hys.- Total / Subtotal
• Abdominal / MINILAP Hysterectomy- Total /
Subtotal
 Surgical Treatment of DUB
Problems: -
 Curettage HYSTERECTOMY
 Mostly diagnostic • Invasive procedure
 Never gives a cure • Not suitable at all
 Endometrial ages
resection / ablation • Not without risks
 Array of methods • Costly
 Recurrence is • First option in 40+
common • DUB is the most
 Amenorrhoea gives
common indication
cure
Need of the Hour for the Treatment of
DUB

The ideal therapy should be a designer drug

which can block the action of Estrogen on
the Endometrium but not its beneficial
actions on other tissues

“Selective Ostrogen Receptor Modulators”

“Designer Oestrogens”
Selective Ostrogen Receptor Modulators
Oestrogen Ligand
Receptor E / SERM / ERD

/ AF 1 & 2 Coregulatory Proteins

Oestrogen Receptor Gene

Ligand Complex Transcription

DNA Oestrogen Tissue Response

Response element Agonistic & or
Antagonistic
Mechanism of Tissue Response
Selective Ostrogen Receptor Modulators

Designed to act in
Estrogens specific ways at each of
the oestrogen receptor
SERMs sites in different tissues

3.ORMELOXIFENE
2.Raloxifene
Toremifene
Droloxifene
Anti Estrogens 1.Tamoxifene
The Ideal Selective Ostrogen Receptor The perfect SERM
Modulator The Search goes on

The ideal SERM is

one that has no
uterine stimulation,
prevents bone loss,
has no risk of breast
cancer, a +ve effect
on lipids &
cardiovascular system
and maintains
cognitive function of Adopted from – Rita de Cassia M Dardes & V Craig Jordan

the brain
 The Ideal Selective Ostrogen Receptor The perfect SERM
Modulator The Search goes on
TISSUE Perfect Ormelo Ralo Tamo
Endometrium AE AE  AE E
Breast AE AE  AE AE
Vagina E E AE AE
Bone E E E E
Liver/CVS E E ?E+ E
CNS E E E? AE

E-Estrogenic, AE-Anti Estrogenic

ORMELOXIFENE The perfect SERM for DUB

Chemical Name-
Trans -7-methyl-2-2-dimethyl-
3-phenyl-4(4-(2-
pyroldinoethoxy)phenyl(-
chroman hydrochloride)

The individual elements of the molecular structure give

a tissue selectivity- different DNA transcriptions in
different tissues

Oestrogen agonist Oestrogen antagonist

ORMELOXIFENE The perfect SERM for DUB
An optimally designed SERM with Varied Tissue
Response
It blocks the cytosol receptors by its competitive
binding affinity over Estradiol.

It not only causes a slow build up of the receptors,

but also causes their prolonged retention.

Its action lasts long after the drug is

withdrawn.
ORMELOXIFENE The perfect SERM for DUB
An optimally designed SERM with Varied Tissue
Response

Estrogen Antagonist in UTERUS & BREAST.

Mild Estrogenic action on Vagina, Bone mineral

density, CNS and Serum Lipids.

No action on Hypothalamic Pituitary Ovarian

function, Thyroid or Adrenal. No Progestational,
Androgenic or Antiandrogenic properties
ORMELOXIFENE The perfect SERM for DUB
An optimally designed SERM with Varied Tissue
Response
INDICATED for the treatment of
Dysfunctional Uterine Bleeding
at ANY AGE.

Offers additional advantage of relief of PMS

in peirmenopausal women.
Not suitable for women desiring pregnancy
because of its contraceptive property.
ORMELOXIFENE The perfect SERM for DUB
An optimally designed SERM with Varied Tissue
Response

Women desiring contraception should use a

barrier contraceptive for first two months
Has been approved for inclusion in the
National Family Welfare Program of Govt. of
India, for Social marketing of Health & Family
Welfare.
ORMELOXIFENE The perfect SERM for DUB

Has an excellent safety profile,very well tolerated

& practically without any undesirable side effects
Few contraindications-
• H/O Liver dysfunction or clinical jaundice
• PCOD
• Cervical Dysplasia, Chronic Cervicitis
• H/O Hypersensitivity to the drug
• Nursing mothers(6months).
• Allergic conditions
• Chronic illness renal disease & TB
ORMELOXIFENE The perfect SERM for DUB

Has an excellent safety profile,very well tolerated

& practically without any undesirable side effects

Precaution-
• Menstrual cycles may be delayed in some
users.
• Is of no concern if tablets have been taken
regularly.
• However if it exceeds 15days rule out
pregnancy.
ORMELOXIFENE The perfect SERM for DUB

Has an excellent safety profile,very well tolerated

& practically without any undesirable side effects

Easy to administer-
Two 60mg tablets twice a week ( for
example, Sunday & Wednesday) for 12
weeks followed by one tablet of 60mg
twice a week for another 12 weeks
ORMELOXIFENE The perfect SERM for DUB
An optimally designed SERM with Varied Tissue
Response
Future possibility of use for-
• Fibromyoma,
• Adenomyosis
• Endometriosis
• Breast cancer (prevention & treatment)
• Osteoporosis (prevention & treatment)
• Menopause management.
ORMELOXIFENE The perfect SERM for DUB

Summary
 Dysfunctional Uterine Bleeding is a very common disorder
at all ages from menarche to menopause.
 Though its pathophysioology is still unclear, Estrogen-
Progesterone imbalance is usually the basis of bleeding.
 Available medical treatment modalities are far from
satisfactory.
 Ormeloxifene, the latest Selective Estrogen Receptor
Modulator, is closest to the perfect SERM, having the
desired antirestrogenic and estrogenic action in different
tissues.
ORMELOXIFENE The perfect SERM for DUB

Summary
 It has a very good safety profile and well tolerated, being
practically devoid of side effects.
 Recently approved for clinical use in INDIA, it is an
effective and safe drug for the treatment of DUB at all
ages, because of its antiestrogenic action on the
Endometrium.
 It is easy to administer and cost effective.
 However extensive large scale clinical trials are
needed to establish its effectiveness and safety
Any Questions?
Please Email- rsnpanda@hotmail.com

Website: - www.dreamwater.net/drsnpanda