ABC of Drospirenione. Is she is an Indian citizen by birth? What is different about drospirenone the progestogen used in Yasmin ?

ABC of Drospirenione. Is she is an Indian citizen by birth? What is different about drospirenone the progestogen used in Yasmin ?

Yasmin  is a new monophasic combined oral  contraceptive   marketed by  Schering Each tablet  contains 3.0 mg   drospirenone and  30 ug   of EE Drospirenone differs   from other progestogens  in COCs .It has diuretic properties due to  antimineralocorticoid activity   . This might help to oppose   the salt and fluid   retaining  effects of EE and so    help symptoms like  bloatedness

Yasmin  has also   been  in a small trail    compared with Microgynon   30   to induce   a very  small  lowering  of mean BP.

Drospirenone acts as an antiandrogen    so the  combination     is an alternative to Dianetle for the treatment of moderately  severe   acne and PCOS.

Dorospirenone with EE  is an oestrogen dominant combination  and   so cannot be   expected   to have     the lower    risk of VTE  associated with   the functionally  antioestrogenic    levonorgestrel of for example   Microgynon  But   the actual   comparative  VTE  risk of Yasmin is  so far unknown.Compared  with other modern pills does Yasmin truly have an advantage  with respect to weight gain ? For the minimal   effect on  body mass of alternatives . A European   multicentre  randomized  trial does indeed show    statistically  lower     body weight   changes   as compared  with the desogestrel containing  Marvelon .

  However     most authorities interpret   this decrement in weight   as due only to dieresis so in long  term use    there is  a maintained slight reduction  of total     body water    compared   with controls . After    allowing  for this diuretic  effect over the two years  of the study there was the same  gradient of weight  gain with  both the products studied . This is most likely  to be just the normal background   increase   and so not   caused  by either   COC .

 Given   the above and considerations  of cost   what  criteria   should  normally be applied  for using   Yasmin ?

Yasmin  is to be  welcomed  as a new    choice   for  appropriate   women   as an alternative to Dianette   and Marvelon which  is clinically  recognized as the best mainstream pill for   acne. It is relatively costly

Interestingly this product  adds some new WHO   4  conditions   for pills it should not be  used in patients at risk  of high potassium  levels  . After  assessing this and all  the usual COC contraindications   in may view  Yasmin  is a useful second line COC as follows

A  clear indication for   oestrogen  as   antiandrogen   therapy  

During COC   follow up as a useful oestrogen   dominant   second   choice for empirical   control of minor side effects   particularly  those associated  with fluid  retention  such as  bloatedness and   cyclical   breast enlargement,. Wether it is better than other COCs  for PMS   type   symptoms   remains    to be established

Raised  BP    the level   being such   as to make  the clinician    consider a  change from the current    formulation   of combined pill but COC    still     clinically  usable  i.e.  BP   increased  but  only to  140/90   which    is the  upper    limit of WHO    for  raised  BP   or may be   a little   above such a    switch    to another COC    rather   than  another method    would   only be if  the BP     were well    below the   160/100   level   which is seen as WHP4  

Gerezette would be   a good  alternative   if the BP   were   not to respond  adequately .

Last  and definitely least  what about weight  if the BMI  is already   > 30 the BNF  rightly   recommends a less oestrogen   dominant   formulation  with   levonorgestrel or northeisterone. Otherwise    anxiety   about weight   gain if coupled   with a history  of acne or of probably fluid   retention with earlier pills   might occasionally  justify   Yasmin.

Where does  Dianette  feature  now   we have   Yasmin  ? Is it  to be seen primarily as an effective treatment  for   acne and  hirsutism ?

Dianette is  an antiandrogen / synthetic oestrogen combination  for    the oral   treatments of  moderately severe   acne  and moderate  hirsutism in  women   especially  when due to PCOS

These  are its indications  but it is also a reliable  anovulant  and often  gives   good cycle   control as well. It   has similar   rules for missed  tablets  interactions with drugs    absolute   and relative   contraindications  and requirements  for a monitoring as COC , But it is not indicated   for use   solely   as an oral contraceptive. It can be   free of charge  to the woman   if the prescription is  marked for contraception or the   symbol  for female.

Dianette  is definitely an oestrogen  dominant   product as shown by its desired effect in PCOS   of permitting EE to raise  SHBG  . So it  must be expected to allow   the oestrogen   similarly    to have relatively   greater   effects  in a pro thrombotic direction than   a levonorgestrel    product   would  and  indeed  vasilalus   et al   2001  found   a four fold  increase  in VTE risk compared  with   levonorgestrel  pills. So  the CSM advice    is that Dianette  is contraindicated   in women with a close FH  of confirmed idiopathic  VTE i.e.     WHO  4 in all circumstances  

There   has been no good  head to head RCT  of Yasmin  versus   diamette but  indirect   evidence    suggests  Yasmin  would  have  almost identical effectiveness for   the conditions for which    Diabette is  indicaed .

With   either   product  caution is essential because   so many prospective  users with PCOS   do have high BMIs . However    the added benefit   due to being  a therapy   and not just    a contraceptive   might be held in many   cases to justify     some added  risk 

Resolution   of acne is usually within    a year yet in may experience   patients develop a very strong  brand loyalty to their   Dianette. The   quoted   SPC  statement    implies   that we should      encourage   them to switch  when their condition   is  controlled to an   oestrogen   dominant COC   . If they  do not   tolerate    the alternative  they might well   accept   Yasmin which   indeed  might nowadays be used  instead of  Dianette   form the outset.

It is  also acceptable ultimately  to return to and continue with Dianette for much longer  than 1 years    assuming the woman accepts  the unlikely but possible hepatic  and pro thrombotic risks.  

Which  skin  conditions  are more   common in COC users ?

Chloasma / melasma : this   pregnancy mask    can develop in women on the  COC  after exposure    to sunlight  just as in pregnancy. The condition can be very slow to fade after  the pill is stopped. Mild  degress can be masked by careful use of  cosmetics and tolerated  if exposure to sun can be reduced  .The    condition  can   also occur/recur  with the POP or other  progestone  only contraceptives  hence  a non hormonal  method   might have to be  chosen .

 Photosensitivity : in   prospective  studies    this  problem   tends to be reported more often in COC   takers   than controls Very    rarely   it might be the  first manifestation   of one of the porphyrias . Once  acquired like Chloasma it tends to be permanent  even   if the pill is   discontinued.

Pemphigoud  gestationis :  if this  serious skin condition occur it absolutely contraindicates  the COC

Hirsutism : is  unlikely to be truly caused by the COC   but may be  helped by an oestrogen   dominant  / antiandrogenic  product  especially Yasmin or Dianette.

Loss   of scalp  hair : there  may be a true  link but not a long     term pill related  problem  . Head  hair   density is always  the resultant of the telogen   and anagen phases In pregnancy    and similarly    in  some women on the COC   a greater   proportion than usual   of the hair is synchronized  into the growth   phase. This is  fine at the time but can lead  to  a  noticeable    synchronized loss some time later-   as is often  reported  in the puerperium .

Telangiectasia rosacea  neurodermatitis  spider  naevi erythema multiforme erythema  nodosum  eczema  and possibly other   skin  disorders all these  have been described   but not  established   as possibly  causally associated   or exacerbated  by COCs in a minority   of women . What is the recommended maximum duration of treatment  with Dianette ?

The  SPC  recommends  withdraw  when resolution    is complete  but repeat courses can be   given if the conditions   recur

There is a   concern   that prolonged high dose  treatment  with CPA  can cause    benign    and malignant live tumours   in rats and   heaptotoxicity   has been described   with the much higher  50   mg plus doses  used by   dermatologists and for prostate cancer therapy . There is   some reassuring   evidence    however   from the4 MILTS study that    the 2 mg  dose as  in Dianette  does not increase    the risk of   such tumours above that  for all the other COCs   

What   action should be taken if such skin problems   present  in a COC taker ?

First  consider discontinuing the COC  Severe  conditions such as  erythema multiforme   or   Pemphigoid gestations would  normally   mean   future  avoidance of this method . if the condition  has an immune allergic basis it is  usually unclear  whether  the COC  steroids are   the actual allergens  According      to the view s of the  woman    herself therefore  and any dermatologist involved  if the condition is relatively  mild she ca be cautiously  re challenged with a low  dose COC  perhaps   containing    a different   progestogen   or with the POP Recurrence   would suggest  another   method.

Does   the COC  cause   gingivitis ? Any other   oral problems ?

Hypertrophic  gingivitis is a rare   but well recognized complication  of COC  use Lesser degrees are more common  as in pregnancy   Symptoms are  minimized by good oral hygiene Dry socket a painful state  after  tooth extraction is also  said to be more common in COC users.

What effect  does the COC have on immune mechanisms. ?

Several   studies on immunoglobulins have suggested that artificial   sex  steroids  can modify immune mechanisms The effects   are of a simirl nature to but less marked than   those associated  with pregnancy A study   from France    however     in which   antibodies  to EE   were reported in patients  suffering from venous    thrombosis    has not been confirmed.

The RCGP   study in particular  among the prospective studies showed an increase in inflammations and some disorders that are believed  to have an immune  basis.   However  as shown   these  are partly   balanced  by a well established   protective  effect against  thryodi over and underactivity   and probably  rheumatoid arthritis Once again as with both malignant and benign  tumorus   combination   OCs   seem to be  capable    of causing   both beneficial  and adverse   effects  within the  same medical   field . Causative associations are not  all proven   by any means   and the magnitude of the effects described