Ormeloxifene - A New Treatment Modality in DUB

August 5, 2011

ORMELOXIFNE - A new Treatment Modality in DUB Dr. Surendra Nath Panda, M.S. Professor of Obstetrics and Gynaecology M.K.C.G. Medical CollegeBerhampur, Orissa, INDIA

ORMELOXIFNE - 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 afect any women from menarchee to menopause
• Often the first clinical diagnosis for any excessive menstrual bleeding
Diagnosis 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 in favour of E2 than E2α

Endocrine Abnormality in DUB
• Ovulation: - Normal
• Phase Change: - Shortened FP
• Endomet. Histology: - Normal
• Menstrual Pattern: - Polymenorrhoea menorhagia

Endocrine Abnormality in DUB
• Ovulation: - Normal
• Phase Change: - Long FP
• Endomet. Histology: - Normal
• Menstrual Pattern: - Oligomenorrhea menorhagia

Endocrine Abnormality in DUB
• Ovulation: Abnormal cor. lut
• Phase change: Short LP
• Endomet Histology: Deficient sec. end.
• Menstrual pattern: Pre mens. spotting menorhagia

Endocrine Abnormality in DUB
• Ovulation: Persistent cor. lut
• Phase change: Long LP
• Endomet Histology: Well dev. sec. end.
• Menstrual pattern: Prolonged cycles

Endocrine Abnormality in DUB
• Ovulation: Anovulation (Insufficient follicles)
• Phase change: Short cycles
• Endomet Histology: Deficient Pro. end.
• Menstrual pattern: Polymenorrhagia menorrhagia

Endocrine Abnormality in DUB
• Anovulation (Polycystic Ovaries)
• Phase change: Prol. Cycles
• Endomet Histology: Pro./ Hyperplastic
• Menstrual pattern: Oligomenorrhoea metropathia haemorrhagica

OVULATIONPHASE CHANGEEND. HISMENSTRUAL PATTERN
NORMALSHORTENED F PNORMALPOLYMENORRHAGIA MENORRHAGIA
NORMALLONG F PNORMALOLIOMENORRHOEA MENORRHAGIA
ABNORMAL COR. LUTSHORT F PDIFICIENT SEC. END.PRE MENS. SPOTTING MENORRHAGIA
PERSISTENT COR. LUTLONG F PWELL DEV. SEC. ENDPROLONGED CYCLES
ANOVULATION (Insufficient follicles)SHORT CYCLESDEFICIENT PRO. ENDPOLYMENORRHAGIA MENORRHAGIA
ANOVULATION (Polycystic Ovaries)POL. CYCLESPRO./ HYPERPLASTICOLIOMENORRHOEA METROPATHIA HAEMORRHAGICA

Medical Treatment for DUB
• HORMONES
• Es+Pr
• Progestogens
• Estrogen
• Androgens + Estrogen
• Danazol

•GnRha
SECOND LINE & mostly Adjuvant
• NSAIDS
• Mefenamic acid
• Ethamsylate
• Antifibrinolytics
• EACA
• Tranexamic acid
• Radiotherapy?

Medical Treatment for DUB
Problems:
• Treatment has to be individualised
• 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 - Endometrial Laser Ablation
• HTEA - Hydrothermal Endometrial Ablation

Surgical Treatment of DUB
ENDOMETRIAL ABLATION:
NON HYSTEROSCOPIC 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
• LAPAROSCOPICALLY ASSISTED V H
• Lap. Hys. - Total/Subtotal
• Abdominal /MINILAP Hysterectomy - Total/Subtotal

Surgical Treatment of DUB
Problems:
• Curettage
• Mostly disgnostic
• Never gives a cure
• Endometrial resection/ablation
• Array of methods
• Recurrence is common
• Amenorrhea gives cure
• HYSTERECTOMY
• Invasive procedure
• Not suitable at all ages
• Not without risks
• Costly
• First option in 40+
• DUB is the most common indication

Need of the Hour for the Treatment of DUB
The ideal therapy should be a designer drug which can block the actin of Estrogen on the Endometrium but not its beneficial actions on other tissues
"Selective Ostrogen Receptor Modulators" "Designer Oestrogens"

The Ideal Selective Ostrogen Receptor Modulator
The ideal SERM is one that has no uterine stimulation, prevents bone loss, has no risk of breast canver, a +ve effect on lipids & cardiovascular system and maintains cognitive function of the brain

TISSUEPerfectOrmeloRaloTamo
EndometriumAEAEAEE
BreastAEAEAEAE
VaginaEEAEAE
BoneEEEE
Liver/CVSEE?E+E
CNSEEE?AE

ORMELOXIFENE
The perfect SERM for DUB
An optimally designec 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 caused their prolonged retention.
Its action lasts long after the drug is withdrawn.

ORMELOXIFENE
The perfect SERM for DUB
And optimally designed SERM with Varied Tissue Response
Estrogen Antagonist in UTERUS & BREAST.
Mild Estrogenic action on Vagina, Bone mineral desity, CNS and Serum Lipids.
No action Hypothalamic Pituitary Ovarian function, Throid or Adrenal. No Progenstational, Androgenic or Antiandorgenic 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 peirmenopausl women.
Not suitable for women desiring pregnancy because of it 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 dysfuntion or clinical jaundice
• PCOD
• Cervical Dysplasia, Chronic Cervicitis
• H/O Hypersensitivity to the drug
• Nursing mothers (6 months).
• 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 15 days 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 -
Tw 60 mg tablets twice a week (for example, Sunday & Wednesday) for 12 weeks followed by one tablet of 60 mg twice a week for another 12 weeks

ORMELOXIFENE
The perfect SERM for DUB
Future possiblity 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 pahophysioology is still unlclear, 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.
• Recenlty approved for clinical use in INDIA, it is an effecive 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

Thank you
Any Questions?
Please Email- rsnpanda@hotmail.com
Website:

www.dreamwater.net/drsnpanda