Tamoxifene

 

Tamoxifen when? Scope & Indications of Tamoxifen as ovulogen:-:- In present day the main and possibly the only indication of prescribing TMX is when there are side effects with CC particularly visual /neurological side effects . Scintillating Scotoma are the main contraindications of CC. Though, in such situation both the drugs (CC & TMX) are to be withheld forthwith but one can use either agent at a lower dose after a gap of 3-6 cycles couple of months.. What is Tamoxifen ??

Tamoxifen  a nonsteroidal  selective estrogen  receptor modulator closely resembles CC .  Like CC TMX occupies  estradiol binding  sites on the  hypothalamic  pituitary axis  and prevents  the negative feedback   effect of estradiol  resulting in increased endogenous gonadotropin secretion. Direct action on the ovary without  involving  hypothalamic pituitary  axis has also  been suggested . The beauty of this product is that unlike clomiphene  tamoxifen acts as an agonist on the estrogen receptors of the endometrium which is beneficial  especially for those suffering  from an adverse response  following the administration of CC. Published literature reported ovulation  rate of 50-90% and pregnancy  rate of 30-50% following TMX  and this is achieved with dose of 20-80 mg.  Women who had thin endometrium with CC exhibited improved  endometrial thickness  when tamoxifen was used for ovulation  induction in the subsequent  cycle. In contrary  to previous literature a recent  RCT significant   lower ovulation rate following TMX  compared to CC in PCOS  women. According to this study CC is more  successful than tamoxifen in PCOS women.

Yes, Tamoxifene  is one of the cheap method for OV induction. The indication is thin Endo after Clomiphene but her age is too less for aggressive tr like gonadotrophins and IUI. So in relatively y young women where  Clomiphene fails or say CC produce side effects like Eye problems in such cases TMX has a role. Dose is 40 mg/ 40mg OD from day 3 to day 7 of cycle.

 

 

Gonadotrophins are quite effective in CC resistant cases but costly . CC has failed after couple of cycles. Now, what are the practical options open to young women in Indian perspective? Once counselling done after several cycles of failed CC, many Indian couple (even uneducated couple) does realize that gonadotrophin is badly needed for them but repent because they are simply unable to afford for G cycle. Put in such a situation (after CC resistant cases) the option remaining to the treating physician to prescribe TMX (as an alternative to Gonadotrophin) and make some compromise. Doctor feel-“Watch- what happens”-.

Not to speak of Gonadotrophins : Many Indians cannot afford further tests so as to why CC resistance has followed: in her case--Unfortunately, many Indian couple cannot afford for usual tests at this juncture - so as to why CC failed in their case. Such tests, if not carried out earlier are 1) AMH .2) AFC, 3) Insulin Resistance, 4) high D2 LH & testosterone 5) DHEASO4, & 6) PRL --not to speak of other costly tests. In such cases further tests so as to find the etiology of CC resistant in particular women. We, Indian doctors have to make many compromises at every step of clinical practice not only in the discipline of reproductive medicine.

Like CC TMX is also an competitive estrogen Antagonist –TMX ,like CC also competitively block the estrogen binding sites at the level of arcuate nucleus of hypothalamus, and stimulate GnRH receptors located at Pit for accentuated release of Pit FSH & LH.

Is there any differential expression of LH over FSH –particularly in CC failure cases? In fact there is about 3-4 fold rise of FSH & LH while someone is on CC. But the differential expression FSH & LH in the aforesaid two types of oral Ovulogens is still under study. I have a feeling this part of CC /TMX have not been adequately explored. It is hoped by many researcher that CC failure is due possibly to over expression of LH in fair number women and is a major cause of CC failure à poor oocyte quality. Those who are biased for TMX they claim such disproportionate rise of LH on cycle days 8-11 is not the case with TMX. I admit that I personally do not know about the differential expression of FSH vs. LH in CC cycles against TMX cycles. But many researcher believe that CC in fair no. of cases more rise of LH during the cycle days of Day 8-Day 10 thereby interfering the oocyte quality. Similarly in some cases of CC induced cycle serum E2 remain at supraphysiological levels –explain partly the reasons of failure of CC cycles. In such women one can use TMX as an iterative if the age of the female partner is< 25 yrs or she cannot afford for gonadotrophin cycle. Some also have claimed that LUF is more than TMX.

Miscarriages rate and multiple preg rates are more or less same with CC and Tamoxifen :- e.g. 10% & ABOUT 22% respectively depending on other associated factors like age of female partner, BMI, androgen excess disorders, Hyperinsulinaemia, serum testosterone etc. But for the oral Ovulogens to be effective the D2 serum E2 should be ideally> 50 pg/ml and not less. Additionally, Women who are contraindicated for CC may also be prescribed few cycles of TMX RY after due counselling. Such contraindications of CC are 1) impairment of hepatic enzymes 2) Eye changes after CC .

Why oral Ovulogens in lieu of gonadotrophins:- The advantages of CC/ Tamoxifen are low incidence of multiple gestations, OHSS, low cost, minimal monitoring, .But we are all aware of the fact that whatever agent we use in fair number of subfertile women CC/TMX become resistant despite appropriate dosage e.g Ov insufficiency, Hyperandrogenism, Insulin resistance ,Elderly women and women with BMI> 30 Kg/M2. In such cases one prescribes oral Ovulogens mostly CC but the doctor concerned is skeptical right from the beginning that CC/TMX may not work.

What to do in CC resistant cases? The causes are Treatment:- one can 50 mg of IM progesterone daily in late luteal phase to suppress LH & FSH levels. But usually gonadotrophins is the usual protocol.

Carry home message: Those who are biased for TMX they claim that CC ingestion cause preferential expression of LH mote than FSH from Pit so there is anovulation with CC . But such disproportionate rise of LH on cycle days 8-11 is not the case with TMX