treatment dub

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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

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Page 1: Treatment Dub

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

Page 2: Treatment Dub

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

Page 3: Treatment Dub

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

Page 4: Treatment Dub

NORMAL

SHORTENED FP

NORMAL

POLYMENORRHOEA MENORHAGIA

Endocrine Abnormality In DUB

OVULATUION : -

PHASE CHANGE: -

ENDOMET.

HISTOLOGY: -

MENSTRUAL

PATERN: -

Page 5: Treatment Dub

NORMAL

LONG F P

NORMAL

OLIGOMENORRHOEA MENORHAGIA

Endocrine Abnormality In DUB

OVULATUION : -

PHASE CHANGE: -

ENDOMET.

HISTOLOGY: -

MENSTRUAL

PATERN: -

Page 6: Treatment Dub

ABNORMAL COR.LUT

SHORT L P

DEFICIENT SEC. END.

PRE MENS. SPOTTING MENORHAGIA

Endocrine Abnormality In DUB

OVULATUION : -

PHASE CHANGE: -

ENDOMET.

HISTOLOGY: -

MENSTRUAL

PATERN: -

Page 7: Treatment Dub

PERSISTENT COR. LUT.

LONG L P

WELL DEV. SEC. END.

PROLONGED CYCLES

Endocrine Abnormality In DUB

OVULATUION : -

PHASE CHANGE: -

ENDOMET.

HISTOLOGY: -

MENSTRUAL

PATERN: -

Page 8: Treatment Dub

ANOVULATION(Insufficient follicles)

SHORT CYCLES

DEFICIENT PRO. END.

POLYMENORRHAGIA MENORRHAGIA

Endocrine Abnormality In DUB

OVULATUION : -

PHASE CHANGE: -

ENDOMET.

HISTOLOGY: -

MENSTRUAL

PATERN: -

Page 9: Treatment Dub

OVULATUION : -

PHASE CHANGE: -

ENDOMET.

HISTOLOGY: -

MENSTRUAL

PATERN: -

ANOVULATION(Polycystic Ovaries)

PROL. CYCLES

PRO. / HYPERPLASTIC

OLIGOMENORRHOEAMETROPATHIA HAEMORRHAGICA

Endocrine Abnormality In DUB

Page 10: Treatment Dub

Endocrine Abnormality In DUB

OVULATION PHASE CHANGE

END. HIST MENSTRUAL PATERN

ANOVULATION(Polycystic Ovaries)

PROL. CYCLES PRO. / HYPERPLASTIC

OLIGOMENORRHOEAMETROPATHIA HAEMORRHAGICA

ANOVULATION(Insufficient follicles)

DEFICIENT

PRO. END.

SHORT CYCLES POLYMENORRHAGIAMENORRHAGIA

PERSISTENT COR. LUT

LONG L P WELL DEV. SEC. END

PROLONGED CYCLES

ABNORMAL

COR.LUTSHORT L P DEFICIENT

SEC. END.PRE MENS. SPOTTING MENORHAGIA

NORMALNORMAL

NORMALNORMAL

SHORTENED F P

LONG F P

POLYMENORRHAGIAMENORRHAGIA

OLIGOMENORRHOEA MENORRHAGIA

Page 11: Treatment Dub

D U B - Management Options

CONSERVATIVE D & C MEDICAL

SPONTANEOUS CURE

RECURENCE D & C FAILURE / RECURENCE

-SURGERY- ENDOMETRIAL ABLATION / HYSTERCTOMY

Page 12: Treatment Dub

HORMONES Es+Pr Progestogens Estrogen Androgens +

Estrogen Danazol GnRha

SECOND LINE & mostly AdjuvantNSAIDsMefenamic acidEthamsylateAntifibrinolytics

• EACA• Tranexamic

acidRadiotherapy ?

Medical Treatment for DUB

Page 13: Treatment Dub

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

Medical Treatment for DUB

Problems: -

Page 14: Treatment Dub

ENDOMETRIAL ABLATION: -

• TCRE – Tran Cervical Resection Of

Endometrium

• ELA – Endrometrial Laser Ablation

• HTEA – Hydrothermal Endrometrial Ablation

HYSTEROSCOPIC METHODS: -

Surgical Treatment of DUB

Page 15: Treatment Dub

• 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)

ENDOMETRIAL ABLATION: -

NON HYSTREOSCOPIC METHODS: -

Surgical Treatment of DUB

Page 16: Treatment Dub

• VAGINAL HYSTERECTOMY

• LPAROSCOPICALLY ASSISTED V H

• Lap Hys.- Total / Subtotal

• Abdominal / MINILAP Hysterectomy- Total /

Subtotal

HYSTERCTOMY: -

Surgical Treatment of DUB

Page 17: Treatment Dub

Surgical Treatment of DUB

Curettage Mostly diagnostic Never gives a cure

Endometrial resection / ablation Array of methods Recurrence is

common Amenorrhoea gives

cure

• HYSTERECTOMY• Invasive procedure• Not suitable at all ages

• Not without risks• Costly• First option in 40+ • DUB is the most common indication

Problems: -

Page 18: Treatment Dub

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”

Page 19: Treatment Dub

Mechanism of Tissue Response

Oestrogen Receptor Ligand Complex

Oestrogen Receptor

Ligand

E / SERM / ERD

DNA Oestrogen Response element

Gene Transcription

Tissue Response Agonistic & or Antagonistic

Coregulatory Proteins / AF 1 & 2

Selective Ostrogen Receptor Modulators

Page 20: Treatment Dub

Selective Ostrogen Receptor Modulators

Estrogens

Anti Estrogens

SERMs

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

3.ORMELOXIFENE

1.Tamoxifene

2.Raloxifene

Droloxifene

Toremifene

Page 21: Treatment Dub

The Ideal Selective Ostrogen Receptor Modulator

The perfect SERM

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

the brain

The Search goes on

Adopted from – Rita de Cassia M Dardes & V Craig Jordan

Page 22: Treatment Dub

The Ideal Selective Ostrogen Receptor Modulator

The perfect SERM

The Search goes on

TISSUE

Endometrium

Breast

Vagina

Bone

Liver/CVS

CNS

Perfect

AE

AE

E

E

E

E

E-Estrogenic, AE-Anti Estrogenic

Tamo

E

AE

AE

E

E

AE

Ralo

AE

AE

AE

E

?E+

E?

Ormelo

AE

AE

E

E

E

E

Page 23: Treatment Dub

ORMELOXIFENE

The individual elements of the molecular structure give a tissue selectivity- different DNA transcriptions in

different tissues

Oestrogen agonist Oestrogen antagonist

The perfect SERM for DUB

Chemical Name-

Trans -7-methyl-2-2-dimethyl-3-phenyl-4(4-(2-

pyroldinoethoxy)phenyl(-chroman hydrochloride)

Page 24: Treatment 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

Page 25: Treatment 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

Page 26: Treatment 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

Page 27: Treatment 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

Page 28: Treatment 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

Page 29: Treatment Dub

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

Page 30: Treatment Dub

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

Has an excellent safety profile,very well tolerated & practically without any undesirable side effects

Page 31: Treatment 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

Page 32: Treatment 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.

The perfect SERM for DUBORMELOXIFENE

Page 33: Treatment Dub

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

The perfect SERM for DUBORMELOXIFENE

Summary

Page 34: Treatment Dub

Any Questions?

Please Email- [email protected]

Website: - www.dreamwater.net/drsnpanda