3. Definition Of HMB
“Excessive menstrual blood loss which
interferes with the woman’s physical,
emotional, social and material quality of life,
and which can occur alone or in combination
with other symptoms.”
Nice guidelines 2007
4. Treatment of DUB
Woman Centred Care
Goals
Control
bleeding
Correct anemia/associated conditions
Prevent recurrence
Improve quality of life
6. Ideal Treatment Choice–Points to
Ponder
Whether cycles are
ovulatory or not
Age
Whether the patient
requires contraception
Desires Fertility
Choice of the patient
7. Pharmaceutical Treatment – Nice Guidelines
First Line
Levonorgestrel-releasing intrauterine
system (LNG-IUS)
Second Line Tranexamic acid (non-hormonal)
Can be used in parallel with
investigations. If
no improvement, stop treatment after 3
cycles
Non-steroidal anti-inflammatory drugs (NSAIDs)
If no improvement, stop treatment after 3
cycles.
Can be used in parallel with investigations
Preferred over tranexamic acid in
dysmenorrhoea
8. Third Line
Oral progestogen
Norethisterone (15 mg) daily from
days 5 to 26 of the menstrual cycle
Injected progestogen
Others
Gonadotrophin-releasing hormone
analogue (Gn-RH analogue)
If used for more than 6 months add
back
HRT therapy is recommended
9. Following Treatment Not Recommended
Oral progestogens in the luteal
phase only
Danazol
Ethamsylate
Dilatation and curettage (D and C)
10. GUIDELINES FOR THE MANAGEMENT OF
ABNORMAL UTERINE BLEEDING
Age, desire to preserve fertility, coexisting medical
conditions, and patient preference are essential
considerations.
For each of the suggested methods, the patient should
be aware of the risks and contraindications to allow
informed choice.
Progestogens given in the luteal phase of the
ovulatory menstrual cycles are not effective in
S O reducing IregularRheavy menstrual Ibleeding.
G C C L I N C A L P A C T I C E G U I D E L N E S 2001
14. Need of the Hour --- Medical Drugs
“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”
16. IDEAL SERM FOR DUB
“An optimally designed SERM with Varied Tissue Response”
17. Ormeloxifene – An Ideal SERM
Dysfunctional uterine bleeding at any age
Relief of PMS in perimenopausal women
For women desiring contraceptive property
Has an excellent safety profile, very well-tolerated
& practically without any undesirable side-effects
18. Ormeloxifene– Dosing Strategy
Convenient dosage – twice or once weekly
60 mg tablets twice a week ( for example, Sunday
& Wednesday) for 12 weeks followed by one tablet
of 60 mg once a week for another 12 weeks
19. Ormeloxifene
CDR Institute Lucknow 1991
Once a week Non Hormonal
Contraceptive
Marketed in India in 1992 as
Saheli and Choice-7 and
Centron
Included in the National Family
Welfare Programme in 1995
20. Efficacy in Dysfunctional Menorrhagia (AIIMS)
PILOT STUDY
Study Population: Forty-two women with menorrhagia were recruited
for the study
Dosage: Ormeloxifene was given to each patient 60 mg twice a week
for 3 months and then once a week for 1 month. Patients were
followed up at 2 and 4 months of therapy, then at 3 and 6 months after
treatment was stopped
Assessments:
Menstrual blood loss (MBL) was measured objectively by a
pictorial blood loss assessment chart (PBAC) score and
subjectively by a visual analog scale (VAS)
J. Obstet. Gynaecol. Res. vol. 35, No. 4: 746–752, August 2009
21. Efficacy in Dysfunctional Menorrhagia
The pretreatment median
PBAC score was 388
(range 169–835)
Median PBAC reduced to
80 (range 0–730) and 5
(range 0–310) at 2 and 4
months, respectively (pvalue <0.001)
J. Obstet. Gynaecol. Res. vol. 35, No. 4: 746–752, August 2009
The percentage reduction
in PBAC score - 97.7% at
Reduction in PBAC Score
22. Efficacy in Dysfunctional Menorrhagia
Amenorrhea with the
therapy – 18 patients
(42.9%)
Adverse effects
included ovarian cyst
(7.1%), cervical
erosion and discharge
(7.1%), gastric
dyspepsia (4.8%),
J. Obstet. Gynaecol. Res. Vol. 35, No. 4: 746–752, August 2009
vague abdominal pain
(4.8%) and headache
Percentage Reduction in PBAC Score
2.3%
97.7%
23. Ormeloxifene Versus MPA in the treatment of
Dysfunctional uterine Bleeding : A DoubleBlind Randomised Controlled Trial
Study Population: 84 women attending gynae OPD in Belgaum India were
.
enrolled , 42 in each arm.
Dosage: Group A – 60 mg ormeloxifene twice a week for 3 consecutive cycles
and Group B – 10 mg MPA from day 5-25 for 3 cycles. All were made to use
same type of sanitary napkins and TVS done for ET before and after treatment
Data Analysis : Mean PBAC score and endometrial thickness were compared
Result: Mean PBAC score reduction of 85.7 % and 54% in group A and B resp
ET reduction was more in Ormeloxifene group but not statistically sign.
Conclusion: oremloxifene is more effective in reducing bleeding than MPA
Journal of South Asian Federation of obstetrics and Gynaecology Jan –April 2011
24. Role of Sevista in the Management of
Dysfunctional Uterine Bleeding
Study Population: 35 cases diagnosed to have DUB after having ruled
out other causes
Dosage: Ormeloxifene was given in the dosage of a 60 mg tablet twice
a week for 3 months, followed by once a week for another 3 months.
Assesment : Hb g/dl and the endometrial thickness before and after
3 months of treatment with sevista.
Observation & results: Statistically significant increase in the Hb g/dl
(p < 0.001) and a statistically significant decrease in the endometrial
thickness (p< 0.001) after the treatment with ormeloxifene.
Conclusion: Ormeloxifene can be used as an effective drug in
the treatment of Dysfunctional uterine bleeding
Dhananjay BS, Sunil Kumar Nanda , Journal of Clinical and Diagnostic Research, 2012.
25. Our Experience ( Over 500 cases)
Indications
1.
Puberty Mennorhagia
Postnatal Bleeding
DUB- after TVS r/o Ovarian Cyst
2.
3.
Dose- 60mg twice weekly for
3months.
Effective upto 1 year after stopping it.
26. Held Back
Postmenopausal Bleeding
2. Endometrial Hyperplasia
3. Infertile patients
4. PCOS
Special mention:
1. In PMB , after balloon therapy – once a week
for 3 months
2. In hyperplasia – along with progesterone's
1.
29. Conclusions
First Line of management of DUB should be
pharmaceutical
Available medical modalities are far from
satisfactory
Important to individualize the treatment
Mirena is the first line of treatment – Nice
Guidelines
30. Thank You
Making one person smile can change the world.
May be not the whole world but their world..
THANK YOU
Notes de l'éditeur
Once DUB has been diagnosed and pathologic causes ruled out, there are several goals of therapy.
No single method is always effective. Many factors play a role in the decision to begin one therapy over another:
age, severity of bleeding, no. of children, desire for fertility
presence of associated pelvic pathology
Inevitably, a profuse but painless menstrual bleed frightens the patient into seeking medical help.
It is paramount that the treating clinician probes the following aspects before initiating the treatment.
Several treatment aspects will be discussed in the subsequent slides. Although many of them look promising there are some serious concerns, which should be clearly understood by the clinician.
Some of the agents for the chronic treatment of DUB include progestational agents, clomiphene citrate, antiprostaglandins, danozol and GnRH analogs.
Surgical management may include hysterectomy or less invasive, uterus-sparing procedures.
Reference:
Ferri: Ferri's Clinical Advisor 2010, 1st ed.
Medical therapy discussed in the previous slides although quite effective, have several limitations. This can be attributed to their direct estrogenic and progesterone action. Research has focused on compounds that are selective for specific tissues thereby minimizing the unwanted effects in some areas and augmenting action in necessary tissues.
The ideal therapy to treat DUB should be a designer drug, which can block the action of estrogen on the endometrium, but not its beneficial actions on other tissues.
Estrogens have agonistic or stimulating effects on all of the estrogen receptor sites
Antiestrogens at the other end of the spectrum have antagonistic effects on the same sites.
SERM’s like tomoxifine, ormeloxifene are designed to act in specific ways at each of the receptor sites.
Reference:
J Clin Oncol 2000 18:3172-3186.
Ormeloxifene is a nonsteroidal, SERM and has been in use as a weekly oral contraceptive for approximately last 20 years, particularly in India, where it was originally developed.
Ormeloxifene interacts with ER, eliciting tissue-specific responses.
It is also undergoing clinical evaluation for the treatment of advanced breast cancer and the prevention of osteoporosis due to its potent antiestrogenic, weak estrogenic and antiprogestational activities.
Reference:
Ormeloxifene (Sevista) Product Monograph. Data on file.
In line with the features discussed earlier, ormeloxifene has all the characteristics of an ideal SERM. Key points are highlighted in this slide.
Reference:
Ormeloxifene (Sevista) Product Monograph. Data on file.
Ormeloxifene can be given as 2 tablets of 60 mg twice a week; every Sunday and Wednesday for the first 12 weeks and then one tablet of 60 mg on the following Sunday/Wednesday for 12 weeks.
Reference:
Ormeloxifene (Sevista) Product Monograph. Data on file.
In another clinical study 42 women with menorrhagia were studied.
Ormeloxifene was given to each patient, 60 mg, twice a week for 3 months and then once a week for 1 month. Patients were followed up at 2 and 4 months of therapy, then at 3 and 6 months after the treatment was stopped.
Investigators measured menstrual blood loss objectively by a PBAC score and subjectively by a Visual Analog scale.
Reference:
J. Obstet. Gynaecol. Res. vol. 35, No. 4: 746–752, August 2009.
The pretreatment median PBAC score was 388 (range 169–835).
Eighteen patients (42.9%) had amenorrhea with the therapy.
Median PBAC reduced to 80 (range 0–730) and 5 (range 0–310) at 2 and 4 months, respectively (p-value <0.001).
Reference:
J. Obstet. Gynaecol. Res. vol. 35, No. 4: 746–752, August 2009
The percentage reduction in the PBAC score was 97.7% at 4 months.
Adverse effects included ovarian cyst (7.1%), cervical erosion and discharge (7.1%), gastric dyspepsia (4.8%), vague abdominal pain (4.8%) and headache (4.8%).
Ormeloxifene is an effective and safe therapeutic option for the medical management of menorrhagia.
Reference:
J. Obstet. Gynaecol. Res. Vol. 35, No. 4: 746–752, August 2009.