Supplementing Prednisolone or Dcadron Tab late at night in a hyperandrogenic ovulatory or anovulatory PCO: Modality & validity of drug therapy??

Supplementing  Prednisolone or Dcadron Tab late at night in a hyperandrogenic ovulatory or anovulatory PCO: Modality & validity of drug therapy??

Decadron to suppress ACTH and in turn to suppress overactive cortex -à thereby decreasing or should I say normalizing raised adrenal androgen producing enzymes DHEASO4. Addition of dexamethasone in  a subfertile hyperandrogenic woman?

Adding dexamethasone to CC cycles in patients with or without increased DHEAS concentrations significantly improves ovulation and pregnancy rates compared to CC, according to a systematic review of randomized controlled studies; however, it also increased multiple pregnancy rates [24]. In addition to suppressing adrenal androgen, dexamethasone partially negates the antiestrogen effect of CC on endometrium [25]. Dexamethasone is administered as a single 0.5 mg tablet at bedtime from cycle day 1 until six days after ovulation. At the Fertility Institute of New Orleans dexamethasone is not used routinely in OI cycles, but is added if serum DHEAS levels are ≥ 180 μg/dL . 

PCOS, Non-PCOS secondary amenorrhoea, all anovulation women, woman suffering from Galactorrhoea, acne, alopecia, hirsutism, Acanthosis nigricans , all obese women-warrant detailed endocrine evaluation to arrive at a definitive diagnosis. These seven groups of women and women heading for induction of ovulation and unexplained infertility mandate detailed but selective endocrine evaluation-though most cannot afford. An experienced astute clinician can select which hormone to test –and other endocrine test at a later date.

PCOS is a syndrome and many diseases can mimic/present as PCOS. Fertile or not fertile -it is not sufficient to simply stamp a woman as PCOS. All PCOS are endocrinologically alike,

We have to find the exact endocrine abnormality in a given PCOS and select most suitable treatment for her. In fact adolescent PCOS also mandate diagnosis of exact endocrine disorder for the origin of PCOS and then select appropriate treatment protocol. In such adolescents- it is more due to cardio-metabolic aberration induced by “Adiponectin-Leptin-Ghrelin-insulin disorder “backed up tyrosine kinase activity disorders.

 In fact we formulate the treatment plan to treat a PCOS on the bases of her hormonal aberration which are not alike in all PCOS. Some exhibit high insulin or high androgen levels, some exhibit hyperprolactinaemia, high DHEASO4 or rarely cortisol. The clinician cannot ask for testing all the six hormones.

Phenotypic analysis helps us to select which hormones to test- test by exclusion.

Oligomenorrhea Similarly, in cases of oligomenorrheic there are many cause mostly endocrine disorder. If she does not want fertility is not an issue, diagnosis by exclusion O subfertile women may be due to following clinical conditions as well. And each disease mandate different treatment protocol for their primary disease and also for treatment of subfertility.

Hirsutism: Such clinical conditions which mimic PCOS (oligomenorrheic/ eumenorrhoic) and with without hirsutism mandate endocrine evaluation to arrive at a definitive clinical diagnosis. Such condition are 1) NC-CAH (Nonclassic adrenal hyperplasia), 2) Cushing syndrome, 3) Virilizing ovarian tumour-all presenting with evidence of hyperandrogenism. The other four conditions which usually present as PCOS 4) hypothyroid, 5) hyperprolactinaemia, 6) acromegaly, and 7) premature ovarian failure (Oligomenorrhoea, weight gain, ovarian enlargement) are. Sometimes 8) drug-related hyperandrogenism may report to us. Elicit detailed drug history before much money is spent on hormone testing with an erroneous diagnosis of PCOS of endocrine disorder.

In cases of dysthyroidism both TSH and T4 measurements are essential.

Premature Ovarian Failure: - One should insist on endocrine confirmation.

Unnecessary hormone testing It is true that selections of endocrine tests is guided by the personal and then present history. We often miss this and do unnecessary hormone testing like androgen levels and PRL, Cortisol, DHEASO4 in all cases of PCOS who do not need it.

Continuum of symptoms:    To whom to consider that it is classical PCOS? The problem is that all the four features of PCIOS are not present in all cases of PCOS and even if present do not express in equal severity. The problem is that symptoms appear as spectrum of symptoms and signs the occurrence which is dissimilar. It is a continuum and we have to add more endocrine tests as clinical signs appear. The usual sequence is Acne/slight hair growthàslight aberrations in M. cyclesàWt gainà

But if a girl was born in mother who had PCOS, hyperandrogenism, dyslipidaemia, & now that mother are diabetic then there is a resin to believe that this adolescent girl is suffering from adolescent Classical PCOS.A low birth weight, premature puberache (appearance of pubic hairs befor the age of 8 years.)-need much vigilance for onward development of PCOS. Puberache is an expression of premature activation of Hypothalamo-Pituitary-Adrenal axis.

The issue of Hyperprolactinaemia.

If two fold raise that will speak of hyperprolactinaemia. In 20-40% of clinically diagnosed PCOS PRL will be slightly raised but to diagnose that PRL is the primary cause of PCOS (no other endocrine disorder) - then there should be at least two fold rise of PRL. This is due to hyperoestrinismà activation of Lactotrophsà more release of PRLà mastodynia, tenderness of breasts and bloating. If less than double level-do not treat by dopamine agonist. Better treat by Insulin sensitizers if unmarried and by OCP if married and does not seek for restoration of fertility Role of estimating 17 hydroxyl progesterone.

This is a screening test for CAH (adult onset type) which is also called as NCAH-non classic Adrenal Hyperplasia.

 The sample should be drawn in early follicular phase and the result should be normally

Stress and Female Subfertility...

Causes of elevated DHEASO4 1) attenuated adrenal enzyme deficiency- proved by ACTH stimulation test; 2) Cushing syndrome & Adrenal Tumours are uncommon causes of raised DHEASO4,

In cases of documented NC-CAH & also in cases where there has been repeated anovulation inspite of CC- then administration of dexamethasone will increase the adrenal pool of androgens.

In some cases it will improve the ovulation rate. 

But after one month of initiation of dexa- morning cortisol should be done to assess the degree of suppression of endogenous cortisol by exogenous Dexa. If cortisol is< 3 mcg./mlàthen the dose of Dexa should be decreased. It is not used in pregnancy,