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 SHORTENED FP

PHASE CHANGE: -

ENDOMET.
HISTOLOGY: -

NORMAL
POLYMENORRHOEA MENORHAGIA

MENSTRUAL PATERN: -

Endocrine Abnormality In DUB

OVULATUION : -

NORMAL LONG F P NORMAL OLIGOMENORRHOEA MENORHAGIA

PHASE CHANGE: -

ENDOMET.
HISTOLOGY: -

MENSTRUAL PATERN: -

Endocrine Abnormality In DUB

OVULATUION : -

ABNORMAL COR.LUT SHORT L P

PHASE CHANGE: -

ENDOMET.
HISTOLOGY: -

DEFICIENT SEC. END.

PRE MENS. SPOTTING MENORHAGIA

MENSTRUAL PATERN: -

Endocrine Abnormality In DUB

OVULATUION : -

PERSISTENT COR. LUT. LONG L P

PHASE CHANGE: -

ENDOMET.
HISTOLOGY: -

WELL DEV. SEC. END.

PROLONGED CYCLES

MENSTRUAL PATERN: -

Endocrine Abnormality In DUB

OVULATUION : -

ANOVULATION (Insufficient follicles)

SHORT CYCLES DEFICIENT PRO. END. POLYMENORRHAGIA MENORRHAGIA

PHASE CHANGE: -

ENDOMET.
HISTOLOGY: -

MENSTRUAL PATERN: -

Endocrine Abnormality In DUB

OVULATUION : -

ANOVULATION (Polycystic Ovaries)

PROL. CYCLES PRO. / HYPERPLASTIC OLIGOMENORRHOEA METROPATHIA HAEMORRHAGICA

PHASE CHANGE: -

ENDOMET.
HISTOLOGY: -

MENSTRUAL PATERN: -

Endocrine Abnormality In DUB

OVULATION PHASE CHANGE
SHORTENED F P

END. HIST

MENSTRUAL PATERN
POLYMENORRHAGIA MENORRHAGIA OLIGOMENORRHOEA MENORRHAGIA

NORMAL NORMAL

NORMAL NORMAL

LONG F P
SHORT L P

ABNORMAL COR.LUT
PERSISTENT COR. LUT

DEFICIENT SEC. END.

WELL DEV. SEC. END

PRE MENS. SPOTTING MENORHAGIA

PROLONGED CYCLES

LONG L P
SHORT CYCLES

ANOVULATION (Insufficient follicles)

ANOVULATION (Polycystic Ovaries)

DEFICIENT PRO. END.

PRO. / HYPERPLASTIC

POLYMENORRHAGIA MENORRHAGIA
OLIGOMENORRHOEA METROPATHIA HAEMORRHAGICA

PROL. CYCLES

D U B - Management Options
CONSERVATIVE D & C MEDICAL

SPONTANEOUS CURE

RECURENCE D & C FAILURE / RECURENCE

-SURGERYENDOMETRIAL ABLATION / HYSTERCTOMY

Medical Treatment for DUB

HORMONES Es+Pr Progestogens SECOND LINE & mostly Adjuvant
NSAIDs Mefenamic acid Ethamsylate Antifibrinolytics EACA Tranexamic acid Radiotherapy ?

Estrogen
Androgens + Estrogen Danazol 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

Mostly diagnostic Never gives a cure

HYSTERECTOMY
Invasive procedure Not suitable at all ages Not without risks Costly First option in 40+ DUB is the most common indication

Endometrial resection / ablation

Array of methods Recurrence is common Amenorrhoea gives 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 Receptor Ligand
E / SERM / ERD AF 1 & 2

Coregulatory Proteins Gene Transcription

Oestrogen Receptor Ligand Complex

DNA Oestrogen Response element

Tissue Response 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

Anti Estrogens

Droloxifene 1.Tamoxifene

The perfect SERM The Ideal Selective Ostrogen Receptor 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 the brain

Adopted from Rita de Cassia M Dardes & V Craig Jordan

The perfect SERM The Ideal Selective Ostrogen Receptor Modulator The Search goes on

TISSUE

Perfect

Ormelo

Ralo

Tamo

Endometrium
Breast Vagina Bone Liver/CVS CNS

AE
AE E E E E

AE
AE E E E E

AE
AE AE E ?E+ E?

E
AE AE E E AE

E-Estrogenic, AE-Anti Estrogenic

ORMELOXIFENE

The perfect SERM for DUB

Chemical Name-

Trans -7-methyl-2-2-dimethyl3-phenyl-4(4-(2pyroldinoethoxy)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 administerTwo 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 forFibromyoma,

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, EstrogenProgesterone 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