Hirsutism (Abnormal Hair Growth in females) - Tips & Tricks in establishing the etiology of hirutism

Diagnosis of polycystic ovary is not an easy task.

The doctors are baffled about the exact diagnosis of PCOS because the diagnostic criteria of PCOS changes with age!!!

The diagnosis of polycystic ovarian syndrome particular in the teenager and young adult group primarily rests on the following clinical, lab. and sonographic tests like i) Clinical (visible) or lab. evidence of HA=Hyper Androgenism, ii) Clinical history of Oligo An=Oligomenorrhoea (infrequent menstrual periods)/Amenorrhoea (cessation of menstrual period more than six months), and iii) Ultra-sonography evidence of PCOM=Polycystic Ovarian Morphology, i.e. large cystic ovaries. But, the clinical problem is that the prevalence of these three different above mentioned diagnostic criteria of PCOS changes with age. The clinical presentation of Oligo-An varies by age, because amenorrhea and oligomenorrhea being common among adolescents, while menstrual cycles may become regular with increasing age in women with PCOS. HA (Excess Androgen i.e. excess male hormone features) partially resolves before menopause in women with PCOS. It’s known to us that ovarian volume and follicle number decrease with age in women both with and without PCOS. It’s also known that in most cases aging may be associated with a defect in insulin action. Therefore, the clinical features and metabolic consequences of PCOS may vary with age, and these age-related changes may affect the observed incidence of PCOS in almost all countries. Therefore there we doctors or any caregiver should remember about these age related change in the menstrual cycle and clinical expression of androgen levels including absence of sonological features of cystic appearance of ovaries.

How many of us are aware thet degree of hyperandrogenism change with advancingage  age incases of PCOS??

We know that elevated serum concentrations of androgens are the most consistent biochemical abnormality and is often considered as  the hallmark of the PCOS syndrome .This conclusion is arrived after the fact that there is an age-related decrease in androgen secretion, as in normal women, such also  occurs in women with PCOS. Many studies have observed that hyperandrogenic women exhibit a negative association between DHEAS levels and age. It has also been observed time and again that  all the three common  serum androgen markers namely, total testosterone, androstenedione, and DHEAS  were significantly negatively correlated with age. Additionally, it have been also observed that  the  incidence of  acne and hirsutism decreased with advanced age,  as is mF-G score, and serum DHEAS levels.

What are the common four phenotypes of PCOS? This is important at least for treatment purpose because till date the treatment of PCOS is mostly empirical and symptom-based As such scientist and reproductive biologists have classified PCOS into four broad phenotypes, though there are many other phenotypes of PCOS. Total 43 phenotypes have been classified by some International Organizations and also by “Androgen Excess and PCO society”. However for day to day clinical practice the following classification seems to be more meaningful.

What are the common four phenotypes of PCOS? This is important at least for treatment purpose because till date the treatment of PCOS is mostly empirical and symptom-based As such scientist and reproductive biologists have classified PCOS into four broad phenotypes, though there are many other phenotypes of PCOS. Total 43 phenotypes have been classified by some International Organizations and also by “Androgen Excess and PCO society”. However for day to day clinical practice the following classification seems to be more meaningful.

a) Phenotype-I PCOS -> Characteristic will be i) Oligomenorrhea/sometimes Secondary Amenorrhea; ii) USG will show evidence of PCOS or PCOM, iii) evidence of hyperandrogenism, iv) Hyperinsulinaemia woman / Normo-insulinoma woman. In 37.5% of such type-I cases there will be clinical and laboratory metabolic syndrome. In fact this is the commonest phenotypes of PCOS as high as 65.6% of PCOS women. If there is documented hyperinsulinaemia then the doctor should seriously consider the Insulin sensitizer has the first or initial drug of choice like i) Metformin, ii) Myoinositol & other isomers, iii) Chr. Pico ate, iv) NAC, v) Vit-D à preferred initial agent will be drugs to combat IR not the Ovulogen).

b) Phenotype-II: This comprises i) Oligomenorrhea,  ii) USG evidence polycystic ovary or PCOM, iii) usually Normo-androgenic women  and 10% will have associated metabolic syndrome (they will need judicious administration of lipid lowering agents) – If at all hyperandrogenaemia then it’ll be better to treat them by OCP as an initial drug. If they seek fertility treatment then it will be prudent to prescribe Pre Tr. with Inj Agonist in previous mid luteal phase or pre tr. with Progesterone, Inj. Progesterone for consecutive five days followed by gonadotrophin Inj. and IUI. All these information’s are mentioned so that many of us don’t unnecessarily carry on with Clomiphene or Letrozole for months together which will be futile induction. Therefore before we prescribe CC or Letrozole it will be again good clinical gesture if some phenotypic classification is made well ahead and a planning a type of induction is rationally designed. These type-II cases are most likely to be CC resistance due to high insulin level. However the prevalence of type-II PCOS in India is about 22.2%.

c) Phenotype-III PCOS: Usually there is i) no Oligomenorrhea (Eumneirrhoic) or very rarely there can be oligomenorrhoea, ii) USG evidence of PCOS, iii) Moderate hyperandrogenism, iv) Minimal number of such PCOS women will have metabolic syndrome. The prevalence of phenotype-III will be only about 1% of PCOS women. –If history is Oligomenorrheaà  Primary agent of Ry will be CC/Anastrazole/ Gonadotrophins in cases who are oligomenorrheic.

d) Phenotype-IV: i) Oligomenorrhea+, b) Ovaries in USG usually normal pattern with normal echogenicity and volume, iii) hyperandrogenism+, iv) metabolic syndrome will be associated in 50% of phenotype-IV PCOS. In fact the prevalence of these phenotypes is 11.2% of all PCOS.

Tips-1: PCOS women seeking fertility restoration – tips for drug selection seeking women. At first one has to assess TSH, Purl. DHESO4. Now after estimating all these three hormones we have to supplement or suppress the hormone milieu. Suppose in there is isolated rise of prolactin hormone, dopamine agonist (cabergoline or bromocripitine) will suffice. But, who demonstrate unusual raise of DHEASO4 and/or T4 then my dear members it will be prudent to find out source of Testosterone by special tests like ACTH stimulation tests, Serum cortisol etc, 17-OH P etc.

Tips-2: If there is abnormal hair growth then she should ideally refer to an Endocrinologist and Cosmetic Surgeon if necessary. In these cases COC alone or in combination with Aldactone will hopefully suffice.

Tips-3: To note that most Obese PCOS, even average weight PCOS women will mandate Lifestyle modification, Exercise, Dietary Modification, Vit-D supplementation if serum level is low, Anti-oxidant to prevent onward vascular damage and only on few occasion some PCOS women will have to take Orlistat (if obesity but overweight women) and lipid lowering agents particularly if triglyceride levels are high.

Tips-4: For instance if LH is high and Ovarian Volume is > 12 CC³à then LOD (laparoscopic Drilling of ovaries) may be given priority to maximize the efficacy of Tr of ovulation   induction..

By contras if there is predominate hyperinsulinaemia in a clinically suspected PCOS then one should can allow fair trial with insulin sensitizers for couple of months without resorting Clomiphene /Anastrazole or gonadotrophin inj-not to speak of ART.

The beauty of insulin sensitizers is those such drugs but not all insulin sensitizers in addition to controlling plasma glucose but also reduce circulating serum   androgens. We should keep in mind that Letrozole reduces or should I say normalizes the ovarian bio synthesis of androgens—in the cortical tissue of ovaries).

AMH is an important marker for female fertility potential. If AMH (A hormone secreted by ovaries) is too low then she is medically called is DOR or POF.

Where is the source of AMH? We want to learn more about AMH. Anti-Müllerian Hormone (AMH) has long been known to provide insight into ovarian function. It is produced by small, growing follicles, thus providing us with quantitative information on ovarian reserve ,The study findings support the hypothesis that AMH levels are biomarker of oocyte and embryo reproductive health besides predicting number of oocyte obtained by COH (Capability of Ovaries to produce eggs by whipping the ovaries by strong high dose hormones called gonadotophins mainly FSH).

In the 21^st century most of us have heard the name of Donor Egg e.g. third party reproduction (by using egg of some other women) is also called egg sharing. This is a variety of artificial reproduction (ART procedure). The egg of other women is only considered when a particular women is unable to produce her own egg due absence of her total no. of eggs which God gave her at the time of birth. The cause of early and speedy loss of all eggs by the age of 35 yrs or say 40 yrs is not known to us with certainty.

When to then consider donor egg if she (POF case) is desirous of a baby to be carried and nourished in her own womb? It’s true that not all women will be considered for donor egg. Some criteria have been framed by different recognized International fertility societies. I’m mentioning one of such criteria where we doctors should seriously counsel about donor egg-to be fertilized with the husband’s sperm and then the young baby so formed inside the test tube is to be transferred (ET-Egg transfer by a special tube) in the recipient (Womb) either in the same cycle or else this newly formed baby (Embryo) may be preserved in the cryocan to be thawed and then put to womb of the desired candidate in a subsequent month after preparing the bed (Endometrium) inside the womb so that the young embryo can get good nutrition once transferred to the prepared womb which is relatively thin and has become small due to stoppage of own female hormones. This entire process is called endometrial preparation- by giving her good amount of estrogens from outside which she can’t produce of her own.

Then when we the doctors should allow a women for receiving a donor egg? Of the four criteria/parameters mentioned below at least two of the following criteria should be present.

1) AMH between O.5 and 1

2) Antral follicle count (follicle between 2-5 mm) less than 4 AF

3) Maternal age more than 40 years.

 4) FSH 3rd day more than 20 IU. &  5) THOSE WOMENPoor responders fit for egg donation.

  Then to summaries the whole issue of counseling about donor egg: What are the criteria of DOR & Egg Donation Programme?

Two of the following criteria must be positive to qualify to receive donor egg.

AMH between .5 and 1

Antral follicle count (follicle between 2-5 mm) less than 4 AF

Maternal age more than 40

FSH 3rd day more than 20 IU

 Poor responders fit for egg donation

Nomo-responders --- FSH 15 -20

Antral Follicle count 5-7

AMH 2-4 (above 5.8 AMH in PCOS)

We all know about AMH in females. How many members are aware of AMH in males? Please try answering. Thanks.

The Sertoli cells secrete a glycoprotein known as anti miillerian hormone (AMH), which causes regression of the paramesonephric duct system in the male embryo and is the likely signal for differentiation of Leydig cells from the surrounding mesenchyme . The Leydig cells produce testosterone nd with the converting enzyme 5a –reductase, dihydrotestosterone. Testosterone is responsible for evolution of the mesonephric duct system into the vas deferens, epididymis, ejaculatory ducts and seminal vesicle. At puberty testosterone leads to spermatogenesis and changes in primary and secondary sex characteristics. Dihydrotestosterone triggers the development of the male external genitalia and the prostate and bullbourethral glands. In the absence of testis determining factor the medulla regresses and the cortical sex cords break up into isolated cell clusters (the primordial follicles ).

The germ cells differentiate into oogonia and enter the first meiotic division as primary oocytes at which point development is arrested until puberty . In the absence of AMH the mesonephric duct system degenerates although in at least one fourth of adult women, remnants may be found in the mesovarium or along the lateral wall of the uterus or vagina .

Egg Donation : When & to whom?? Egg donation has been used to treat human infertility for over 3 decades, and remains an integral part of ART setups. The technique is rapidly gaining popularity in developing countries including India. Specific causes amenable to oocyte donation include surgical oophorectomy, irreversible gonadal damage after chemotherapy/radiotherapy, turner syndrome and other chromosomal aberrations causing gonadal dysgenesis.

What is the main cause of early ovarian failure (POF-DOR)?? The etiology of POF is many:--The common causes are mentioned below:- 1) chromosomal, 2) autoimmune, 3) iatrogenic, 4) infectious, and other many CAUSES where science cant progress.,These are medical terminology called in Idiopathic( NOT UNDERSTADABLE in spite of many many costly tests)..

Then where we doctors should seriously consider DONOR PROGRAAME? To all women? Certainly not to all DOR.
The specific causes deemed suitable for oocyte donation include surgical oophorectomy, irreversible gonadal damage after chemotherapy/radiotherapy, Turner syndrome and other chromosomal aberrations causing gonadal dysgenesis. In addition, oocyte donation may be preventing the transmission of a genetic disease in cases in which the carrier status of both partners is known. Overall, this technique provides women with POF or a diminished ovarian reserve (DOR), with a very realistic chance of pregnancy._

Repeated in Vitro Fertilization Failure and/or fertilization is there in the test tube but when such fertilized egg is place in the womb it doesn’t grow (implantation failure). These are not uncommon for variety of reasons. I will let you know the details the shortcomings i.e. a failure of fertilization of own egg or failure of implantation in the womb. Unfortunately these are becoming and except aged women and pollution of various kinds, we have no answers for these two problems. Any member can comment and add thereby highlight us why it so occurs. We have to know in detail about these because as I said these are not is an uncommon and any member can become devoted of research in these two aspects. Hundreds of infertile women will bless the researchers find out a remedy of utilizing own eggs when these are still produce/manufactured at her ovaries.