ORMELOXIFENE- A New Treatment Modality in 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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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

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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?

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Endocrine Abnormality In DUB
NORMAL SHORTENED FP NORMAL POLYMENORRHOEA
MENORHAGIA

• OVULATUION -
• PHASE CHANGE -
• ENDOMET. HISTOLOGY -
• MENSTRUAL PATERN -

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Endocrine Abnormality In DUB
NORMAL LONG F P NORMAL OLIGOMENORRHOEA
MENORHAGIA

• OVULATUION -
• PHASE CHANGE -
• ENDOMET. HISTOLOGY -
• MENSTRUAL PATERN -

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Endocrine Abnormality In DUB
ABNORMAL COR.LUT SHORT L P DEFICIENT SEC.
END. PRE MENS. SPOTTING MENORHAGIA

• OVULATUION -
• PHASE CHANGE -
• ENDOMET. HISTOLOGY -
• MENSTRUAL PATERN -

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Endocrine Abnormality In DUB
PERSISTENT COR. LUT. LONG L P WELL DEV. SEC.
END. PROLONGED CYCLES

• OVULATUION -
• PHASE CHANGE -
• ENDOMET. HISTOLOGY -
• MENSTRUAL PATERN -

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Endocrine Abnormality In DUB

• OVULATUION -
• PHASE CHANGE -
• ENDOMET. HISTOLOGY -
• MENSTRUAL PATERN -

ANOVULATION (Insufficient follicles) SHORT
CYCLES DEFICIENT PRO. END. POLYMENORRHAGIA
MENORRHAGIA

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Endocrine Abnormality In DUB

• OVULATUION -
• PHASE CHANGE -
• ENDOMET. HISTOLOGY -
• MENSTRUAL PATERN -

ANOVULATION (Polycystic Ovaries) PROL. CYCLES
PRO. / HYPERPLASTIC OLIGOMENORRHOEA METROPATH
IA HAEMORRHAGICA
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Endocrine Abnormality In DUB
OVULATION
PHASE CHANGE
END. HIST
MENSTRUAL PATERN
NORMAL
NORMAL
SHORTENED F P
POLYMENORRHAGIA MENORRHAGIA
NORMAL
LONG F P
NORMAL
OLIGOMENORRHOEA MENORRHAGIA
ABNORMAL COR.LUT
SHORT L P
DEFICIENT SEC. END.
PRE MENS. SPOTTING MENORHAGIA
PERSISTENT COR. LUT
LONG L P
WELL DEV. SEC. END
PROLONGED CYCLES
DEFICIENT PRO. END.
SHORT CYCLES
POLYMENORRHAGIA MENORRHAGIA
ANOVULATION (Insufficient follicles)
OLIGOMENORRHOEA METROPATHIA HAEMORRHAGICA
PROL. CYCLES
PRO. / HYPERPLASTIC
ANOVULATION (Polycystic Ovaries)
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D U B - Management Options
CONSERVATIVE ? ? ? ? D C ? ? ? ? MEDICAL
? ?
? SPONTANEOUS CURE
? ? ?
? ?
?
RECURENCE ? ? ? ? D C ? ? FAILURE
/ ?
RECURENCE ?
?
? ?
? ?
-SURGERY- ENDOMETRIAL ABLATION / HYSTERCTOMY
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Medical Treatment for DUB

• SECOND LINE mostly Adjuvant
• NSAIDs
• Mefenamic acid
• Ethamsylate
• Antifibrinolytics
• EACA
• Tranexamic acid
• Radiotherapy ?

• HORMONES
• EsPr
• Progestogens
• Estrogen
• Androgens Estrogen
• Danazol
• GnRha

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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

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Surgical Treatment of DUB
ENDOMETRIAL ABLATION -

• HYSTEROSCOPIC METHODS -

• TCRE Tran Cervical Resection Of Endometrium
• ELA Endrometrial Laser Ablation
• HTEA Hydrothermal Endrometrial Ablation

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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)

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Surgical Treatment of DUB
HYSTERCTOMY -

• VAGINAL HYSTERECTOMY
• LPAROSCOPICALLY ASSISTED V H
• Lap Hys.- Total / Subtotal
• Abdominal / MINILAP Hysterectomy- Total /
  Subtotal

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Surgical Treatment of DUB
Problems -

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

• Curettage
• Mostly diagnostic
• Never gives a cure
• Endometrial resection / ablation
• Array of methods
• Recurrence is common
• Amenorrhoea gives cure

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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
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Mechanism of Tissue Response
Selective Ostrogen Receptor Modulators
Oestrogen Receptor
Ligand E / SERM / ERD
? / ?
AF 1 2
Coregulatory Proteins
Oestrogen Receptor Ligand Complex
Gene Transcription
DNA Oestrogen Response element
Tissue Response Agonistic or Antagonistic
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Selective Ostrogen Receptor Modulators
Designed to act in specific ways at each of the
oestrogen receptor sites in different tissues
Estrogens
SERMs
3.ORMELOXIFENE
2.Raloxifene
Toremifene
Droloxifene
Anti Estrogens
1.Tamoxifene
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The Ideal Selective Ostrogen Receptor Modulator
The perfect SERM
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
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The Ideal Selective Ostrogen Receptor Modulator
The perfect SERM
The Search goes on
TISSUE Endometrium Breast Vagina Bone Liver/CVS CN
S
Perfect AE AE E E E E
Tamo E AE AE E E AE
Ralo AE AE AE E ?E E?
Ormelo AE ? AE ? E ? E ? E ? E ?
E-Estrogenic, AE-Anti Estrogenic
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ORMELOXIFENE
The perfect SERM for DUB
Chemical Name- Trans -7-methyl-2-2-dimethyl-3-phe
nyl-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
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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.
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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
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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.
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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.
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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

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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.

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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
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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.

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Summary
ORMELOXIFENE
The perfect SERM for DUB

• 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.

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Summary
ORMELOXIFENE
The perfect SERM for 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

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Thank you
Any Questions? Please Email- rsnpanda_at_hotmail.com
Website - www.dreamwater.net/drsnpanda