11. INJ DMPA IS GIVEN INITIALLY
THEN ORMELOXIFENE -- PROVIDES
CONTRACEPTION AND CONTROL OF BLEEDING
12. FIRST 3 - 6 MONTHS – THE DIFFICULT PERIOD
EXTREMELY GOOD RESPONSE
13. TVS IN ALL PATIENTS
ENDOMETRIAL BIOPSY
TO RULE OUT HYPERPLASIA
14. 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
15. 1. 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
22. Medical Management remains the first line
Option has to be individualised
No medication so far is satisfactory
Let us be selective, develop our own
wealth of experience and share
25. “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
26. Woman Centred Care
Goals
Control bleeding
Correct anemia/associated conditions
Prevent recurrence
Improve quality of life
28. Whether cycles are ovulatory
or not
Age
Whether the patient requires
contraception
Desires Fertility
Choice of the patient
29. 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
Combined oral contraceptives
Pharmaceutical Treatment – Nice Guidelines
30. 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
31. Oral progestogens in the luteal phase only
Danazol
Ethamsylate
Dilatation and curettage (D and C)
32. Medical treatment is an effective first line
therapeutic option for abnormal uterine
bleeding.
Tailored to the individual woman’s
therapeutic goals, desire for contraception,
underlying medical conditions, and tolerance
of side effects
33. Cyclic or Predictable in timing
Non-hormonal options such as non-
steroidal anti-inflammatory drugs and
antifibrinolytics
Who desire effective contraception.
COC, INJ DMPA, LNG-IUS
34. Cyclic luteal-phase progestins do not
effectively reduce blood loss and therefore
should not be used as a specific
treatment for heavy menstrual bleeding
Medical or Surgical treatments have failed
or are contraindicated :
Danazol and gonadotropin-releasing
hormone agonists
38. “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”
41. It blocks the cytosol receptors by its competitive binding affinity over
Estradiol
It’s action lasts long after the drug is withdrawn
The long elimination of the half-life of ormeloxifene provides a basis for a
weekly dosing schedule1
It is estrogen antagonist in Uterus & Breast and has mild estrogenic action on
vagina, Bone mineral density, CNS and Serum Lipids2
No action on Hypothalamic Pituitary Ovarian function, Thyroid or Adrenal
No Progestational, Androgenic or Antiandrogenic properties2
42. 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
43. 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
44. 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
45. 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
46. 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 (p-value <0.001)
The percentage reduction in
PBAC score - 97.7% at 4 months
J. Obstet. Gynaecol. Res. vol. 35, No. 4: 746–752, August 2009
Reduction in PBAC Score
47. 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%), vague
abdominal pain (4.8%) and
headache (4.8%)
J. Obstet. Gynaecol. Res. Vol. 35, No. 4: 746–752, August 2009
Percentage Reduction in PBAC ScorePercentage Reduction in PBAC Score
97.7%97.7%
2.3%2.3%
48. Journal of South Asian Federation of obstetrics and Gynaecology Jan –April 2011
.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
50. Indications
1. Puberty Mennorhagia
2. Postnatal Bleeding
3. DUB- after TVS r/o Ovarian Cyst
4. Mirena Users – immediate 3 months
Dose- 60mg twice weekly for 3months.
Effective upto 1 year after stopping it.
51. 1. 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
56. Role of Ormeloxifene in benign Mastalgia of diverse origin
Paper No 779 presented by Dr. Subrat kumar Mohakul and Dr. Sujatha Guttala. on 18th
Jan 2013 at 56th AICOG 2013,
58. 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
Ormeloxifene is safe, efficacious, cheap and easy to
administer.
59. ADDRESS
11 Gagan Vihar, Near Karkari Morh
Flyover, Delhi - 51
CONTACT US
9650588339, 011-22414049,
WEBSITE :
www.lifecarecentre.in
www.drshardajain.com
www.lifecareivf.com
E-MAIL ID
Sharda.lifecare@gmail.com
Lifecarecentre21@gmail.com
info@lifecareivf.com
&
Thank You
60. Thank YouThank You
THANK YOU
Making one person smile can change the world.
May be not the whole world but their world..
Hinweis der Redaktion
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.
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.
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&apos;s Clinical Advisor 2010, 1st ed.
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&apos;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.
Several key features of ormeloxifene are shown in this slide.
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 even after the drug is withdrawn.
The long elimination of the half-life of ormeloxifene provides a basis for a weekly dosing schedule.
It is the estrogen antagonist in the uterus and breast and has mild estrogenic action on vagina, bone mineral density, CNS and serum lipids.
No action on hypothalamic pituitary ovarian function, thyroid or adrenal and has no progestational, androgenic or antiandrogenic properties.
References:
J. Obstet. Gynaecol. Res. vol. 35, No. 4: 746–752, August 2009.
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 &lt;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.
Ormeloxifene vs MPA
CONTEMPORARY PERSPECTIVE STUDY
Ormeloxifene versus Medroxyprogesterone Acetate (MPA) in the Treatment of Dysfunctional Uterine Bleeding: A Double-Blind Randomized Controlled Trial
Jyotsna Shravage, D Mekhala, MB Bellad, MS Ganachari, HA Dhumale
[Year:2011] [Month:January-April] [Volumn:3 ] [Number:1] [Pages:55] [Pages No:21-24]
[Journal of South Asian Federation of Obstetrics and Gynecology]
ABSTRACT
Objective: To find the effectiveness of ormeloxifene vs medroxyprogesterone acetate (MPA) to reduce blood loss in dysfunctional uterine bleeding (DUB).
Materials and methods:
Design-A double blind randomized controlled trial.
Data source-The women attending gynecology OPD in teaching hospital attached to Jawaharlal Nehru Medical College, Belgaum, India for menorrhagia, meeting the selection criteria were enrolled into the study.
Randomization-Computer-generated randomization, with block size of two, was done into two groups.
Intervention-One group (group A) received capsule ormeloxifene 60 mg to be taken two days a week at an interval of 3 days, and a placebo form of medroxyprogesterone acetate for 21 days starting from day 2 to 5 of the menstrual cycle for three consecutive cycles. Other group (group B) received medroxyprogesterone acetate (MPA) 10 mg for 21 days starting from day 2 to 5 of the menstrual cycle, and a placebo form of ormeloxifene for 2 days a week with an interval of 3 days for three consecutive cycles. The drug and its placebo were in similar capsular form. All the participants were ensured to use the similar type of sanitary napkins, and transvaginal ultrasonography was done to note the endometrial thickness (ET) before and after the drug therapy.
Blinding-The department of clinical pharmacy prepared the drug packets and kept the randomization code till the data was analyzed, thus ensuring the double blinding.
Outcome: Participants were interviewed during subsequent cycle. Pictorial blood assessment chart (PBAC) score was used to calculate blood loss during menses at the first and subsequent three months.
Data analysis: The mean PBAC scores and endometrial thickness were compared in two groups.
Results: The mean pretreatment PBAC scores in group A and group B were 262.26 and 238.71 ml respectively. The mean PBAC scores at the end of the study period were 73 and 108 in group A and B respectively, reporting an overall reduction in mean blood loss by 85.7 and 54.76% (p = 0.0205) in group A and B respectively. Thus, there was a significant reduction in blood loss in the group receiving ormeloxifene. The reduction in the mean endometrial thickness was more in ormeloxifene group. However, this was not statistically significant (p = 0.0942).
Conclusion: Ormeloxifene is more effective as compared to MPA in reducing the blood loss in the treatment of DUB.
Keywords: Ormeloxifene, Progesterone, Medroxyprogesterone acetate (MPA), Dysfunctional uterine bleeding.
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.