Tamoxifene -How useful as an ovulation inducing agent

 

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..

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