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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
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
NORMAL
SHORTENED FP
NORMAL
POLYMENORRHOEA MENORHAGIA
Endocrine Abnormality In DUB
OVULATUION : -
PHASE CHANGE: -
ENDOMET.
HISTOLOGY: -
MENSTRUAL
PATERN: -
NORMAL
LONG F P
NORMAL
OLIGOMENORRHOEA MENORHAGIA
Endocrine Abnormality In DUB
OVULATUION : -
PHASE CHANGE: -
ENDOMET.
HISTOLOGY: -
MENSTRUAL
PATERN: -
ABNORMAL COR.LUT
SHORT L P
DEFICIENT SEC. END.
PRE MENS. SPOTTING MENORHAGIA
Endocrine Abnormality In DUB
OVULATUION : -
PHASE CHANGE: -
ENDOMET.
HISTOLOGY: -
MENSTRUAL
PATERN: -
PERSISTENT COR. LUT.
LONG L P
WELL DEV. SEC. END.
PROLONGED CYCLES
Endocrine Abnormality In DUB
OVULATUION : -
PHASE CHANGE: -
ENDOMET.
HISTOLOGY: -
MENSTRUAL
PATERN: -
ANOVULATION(Insufficient follicles)
SHORT CYCLES
DEFICIENT PRO. END.
POLYMENORRHAGIA MENORRHAGIA
Endocrine Abnormality In DUB
OVULATUION : -
PHASE CHANGE: -
ENDOMET.
HISTOLOGY: -
MENSTRUAL
PATERN: -
OVULATUION : -
PHASE CHANGE: -
ENDOMET.
HISTOLOGY: -
MENSTRUAL
PATERN: -
ANOVULATION(Polycystic Ovaries)
PROL. CYCLES
PRO. / HYPERPLASTIC
OLIGOMENORRHOEAMETROPATHIA HAEMORRHAGICA
Endocrine Abnormality In 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
D U B - Management Options
CONSERVATIVE D & C MEDICAL
SPONTANEOUS CURE
RECURENCE D & C FAILURE / RECURENCE
-SURGERY- ENDOMETRIAL ABLATION / HYSTERCTOMY
HORMONES Es+Pr Progestogens Estrogen Androgens +
Estrogen Danazol GnRha
SECOND LINE & mostly AdjuvantNSAIDsMefenamic acidEthamsylateAntifibrinolytics
• EACA• Tranexamic
acidRadiotherapy ?
Medical Treatment for 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: -
ENDOMETRIAL ABLATION: -
• TCRE – Tran Cervical Resection Of
Endometrium
• ELA – Endrometrial Laser Ablation
• HTEA – Hydrothermal Endrometrial Ablation
HYSTEROSCOPIC METHODS: -
Surgical Treatment of 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
• VAGINAL HYSTERECTOMY
• LPAROSCOPICALLY ASSISTED V H
• Lap Hys.- Total / Subtotal
• Abdominal / MINILAP Hysterectomy- Total /
Subtotal
HYSTERCTOMY: -
Surgical Treatment of 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: -
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”
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
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
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
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
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)
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
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
Has an excellent safety profile,very well tolerated & practically without any undesirable side effects
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.
The perfect SERM for DUBORMELOXIFENE
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