Myoma

Ulipristal / Mifepristone in medl management of Myoma:-Know about fibroids:-Possibly as many as 80% of all women have uterine fibroids. While the majority usually have no symptoms, 1 in 4 end up with symptoms severe enough to require treatment . List is long like ‘multiple choice questions”:-There are many agents used for medical management of symptomatic myoma. The list of such drugs is long 1) NSAIDs-when Menorrhagia-related to myoma is the chief concern. However such myoma-related meno can be controlled  as well by  2) COC  or Progestins-if myoma-related symptoms are limited to  periods  only—by causing thinning of endo 3) LNG-IUS –if there is no cavitary irregularities 4) Androgens-like Danazol / Gestrinone –not favored for their unacceptable side effects 5) Agonists as either Monthly basis 3.75 mg ( as IM or Sub cut)-/ Long acting 11.25mg  –on 3 monthly basis along with add back Ry -like COC(usually cyclically  Premarin for 25 days a month  along with MPA 10 mg × for 10 days per month)/ or continuous Premarin 0.625 & MPA 2.5 mg tablets to prevent primarily bone lisp(-in fact bone loss in Trabecular bone will be >6%  after 6 months of agonist Inj if no add back) is concurrently supplemented. As an add back Ry:-Tibolone / Raloxifene are also used occasionally but costlier –these are family of SERMs. 6) In research settings Antagonists have also been used with good success but frequency of Inj are unacceptable even in depot form 7) Mifepristone / Ulipristal:-SERMs... A word of caution:-No 6 & 7 has not been approved by any International / National Drug Regularly Authority. UPA.

3) Myoma & UPA (Ulipristal Acetate) Disadvantages of UPA? UPA has some adverse endometrial effects.  As

Not all myoma are alike: The annual growth rate of myoma of Ms X & Ms Y is different and  explanation for this not clear to me . Can U highlight this i e differential growth rate of myoma ?  Neither  all women  exhibiting Myoma in USG warrant medical Tr.  So take home message is not  to prescribe drugs whenever a myoma is visualized in USG or clinically become palpable. Members opinion on speed of growth of myoma annual basis

 What is the usual growth rate of myoma?? The usual growth per annum is 0.5 cm per yr but some myoma can be faster growing as 3 cm/yr. Some will spont regress of its own without medication. If a woman is aged and myoma hinders sonographic visualization of adenexae   then it becomes an indication for medl TR –so that USG can reduce the tumour to certain extent-enabling gonads to visualize and asses properly.

Home task for members. Members have failed to discover drugs/ vaccine against C Virus. Now can they discover which women will respond favorably to  which drug in myoma cases?? Back to Basics:-Can we dream that a day will come when it will be possible to predict the therapeutic efficacy of medl agents prescribed for myoma e.g.  UPA/ Mifepristone/ or Asoprisnil (newborn) by receptor assay ?

Selection of drug-as is often done prior to ovulation induction==”right drug for right women “  ?? Can we forecast /predict efficacy of anti-myomatous drugs , as is done while choosing the  anticancer  drugs for Br Ca –type of Receptor and its sensitivity to the antineoplastic drugs and thereby avoiding prescribing costly drugs which is not going to exert any desirable effect on myoma .

 Dynamics of action in the myomatous tumors cells? Are all the tumors in a particular woman will show same population of progesterone receptors identically? Will a day come we can assess the drug sensitivity by FNAC of myoma à thereby selecting the most effective drug. Hope for the best!!! It is tea break now. Will return at 1800hrs.

 -Genetics of Myoma:--What is the present concept of etiology/pathogenesis of Myoma??   It is surprising to know that most of myoma is due to karyotypic defects!!! A many as 40% of myomatous casesà exhibit Karyotypic defects. In fact myomatous cells are derived from progenitor myocyte -as such multiple tumors while harboring inside the same uterus can have independent chromosomal make up and varying response to exogenous drugs. Quite logically, diff myomatous (in a same woman) -cells can exhibit diff response to diff hormones, facilaitiary growth factors or prohormone.

By and large most myomas exhibit defects in Chr No. 6,7,12 & 14 and rarely in X,1,3,10,13  and more we know about the what went wrong in a woman with that particular chromosome is a prophylaxis for dev myoma.

Erratic behavior of Myocyte in  some women? Why such excess susceptibility (hyper response)  to normally circulating progesterone?  Ans: The  exact answer  is not known to us ,Possibly too many progesterone Type A receptors  are densely populated in immature myocyte  backed up by some  growth factors and genes . WE are aware of the fact that all steroid receptors are not present on the cytoplasmic membrane. Instead steroid receptors are present on nuclear mm only .In case of symptomatic myoma at relatively young age we intend to have selective action on some special myocyte some of which have by chance propensity to  grow erratically under the influence of genes and some growth factors potentiated by progesterones  .

Explanation of the dynamics of   Mifepristone or Ulipristal: The  two common drugs used for medical management of myoma are   Mifepristone or  Ulipristal: But how exactly they act inside the human body??:: Basically  we the treating physicians  intend to damp down the progestational activity at selective areas of body (SPRM).Most of the myoma are progesterone dependent while  most of endometriosis are dependendent on Oestrogens.  In  case of Myoma we intend to have selective action on some special Myocytes some of which grow erratically. We know that drugs are prescribed only in case of symptomatic myoma. Having admitted that and the fact myoma may recur after the completion of scheduled medl management course there is a big therapeutic scope for medical Tr of myoma:-By any means our objective is to quite   the progesterone receptors at myocyte.

Now it is time to understand that there are different receptors of progesterone?? Which type of receptor is commonly observed   in myomatous cells? - Out of the two known receptors of Progesterone (PR-A & PR-B) -- it is the A type that are more frequently seen densely (much more) than B at tumor cells. So PRMs,(progesterone receptor modulators )  are also called as Anti progestins-. Such drugs effects by exerting antagonistic effects on receptors of progesterone-at selective sites .That is why such class of drugs are aptly termed as SELECTIVE.

  Which drug in which cases??  A) where bleeding (Menorrhagia) is not the primary concern. If meno is primary intention to treat them NSAID & COC. Such agents  should be considered first à or LNG IUS if there is no Cavitary distortion. By that I don’t mean  that classical drugs for myoma I e. Ulipristal (costly) ,&  mifepristone:- wont working bleeding cases but these are costly, So a fair trial with less costly drug seems better.

Given choice which SPRM is better in myoma if cost is not a factor??     -First choice is still Ulipristal (costly) , second choice will be mifepristone:- The idea to perform intermittent, rather than continuous, treatment courses were developed to address concerns including the safety of SPRMs UPA has with antiproliferative effects on fibroid cells.

http://fertstertforum.com/gallianod-ulipristal-acetate-uterine-fibroids/

How effective is mifepristone  in myoma?? Mifepristone reduces the volume of myoma by 50%. People have used Mifepristone as 2.5 mg, 5, 10, even 50 mg for over 3 months continuously. But then again there are some associated medl disorders where Mifepristone can’t be used e.g. those who are on steroid Ry for some other diseases, on Aspirins, smokers, hepatic-renal parenchymal diseases.