Medical management of dub – new modalities dr. jyoti bhaskar lecture 4

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  • 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.
  • Medical management of dub – new modalities dr. jyoti bhaskar lecture 4

    1. 1. Lecture - 4 MEDICAL MANAGEMENT OF DUB – NEW MODALITIES Dr. Jyoti Bhaskar “Save Uterus Campaign” Lecture Series (1 to 4 )
    2. 2. MEDICAL MANAGEMENT OF DUB – NEW MODALITIES Dr.Jyoti Bhaskar Dr. Sharda Jain Dr. Jyoti Agarwal
    3. 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. 4. Treatment of DUB Woman Centred Care  Goals  Control bleeding  Correct anemia/associated conditions  Prevent recurrence  Improve quality of life
    5. 5. MINIMAL ACCESS SURGERY MEDICAL RX HYSTERECTOMY Any interventions should aim to improve quality of life measures. [D] -- NICE guidelines
    6. 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. 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. 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. 9. Following Treatment Not Recommended Oral progestogens in the luteal phase only  Danazol  Ethamsylate  Dilatation and curettage (D and C) 
    10. 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
    11. 11. DUB – Medical Management Options – Progestational agents       Medroxyprogesterone acetate, Norethisterone Depo-medroxyprogesterone Oral contraceptives Levonorgestrel-releasing intrauterine device Clomiphene citrate . Other – Antiprostaglandins, antifibrinolytics,
    12. 12. Comparative Efficacy Percentage reduction in blood loss Mirena Placebo Prostaglandins Synthetase Inhibitor TA COCs 0 -25 -50 -75 Decrease % -100
    13. 13. QUEST GOES ON ………
    14. 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”
    15. 15. SERM’s – The Designer Estrogens Estrogens SERMs Tamoxifine Droloxifine Toremifine Raloxifine Ormeloxifine J Clin Oncol 2000 18:3172-3186. Antiestrogens
    16. 16. IDEAL SERM FOR DUB “An optimally designed SERM with Varied Tissue Response”
    17. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.
    27. 27. Our Observations  Ovarian Cysts
    28. 28. Endometrial thickness
    29. 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. 30. Thank You Making one person smile can change the world. May be not the whole world but their world.. THANK YOU

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