Polycystic Ovarian Syndrome PCOS

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Polycystic Ovarian Syndrome PCOS

The Polycystic Ovarian Syndrome PCOS:

Polycystic Ovarian Syndrome

Definition:

Polycystic ovary syndrome (PCOS) is a set of symptoms due to elevated androgens in females, and it is the main ovarian disfunction.[1]

Overview of Polycystic Ovarian Syndrome:

This heterogenous disorder is characterized by excessive androgen production by the ovaries mainly. PCOS is a multifactorial and polygenic condition. Diagnosis is based upon the presence of any two of the following three criteria

Oligo and/or anovulation.
Hyperandrogenism (clinical and/or biochemical).
Polycystic ovaries.

Another etiologist (CAH, thyroid dysfunction, hyperprolactinemia, Cushing syndrome) are to be excluded. The incidence varies between 0.5–4 percent, more common amongst infertile women.

It is prevalent in young reproductive age group (20–30%). Additionally, Polycystic ovary may be seen in about 20% of normal women.[1]

Pathophysiology

Exact pathophysiology of PCOS is not clearly understood. It may be discussed under the following heads (scheme–6) i.e.:

(a)Hypothalamic pituitary compartment abnormality.

(b) Androgen excess

(d) Obesity also insulin resistance.

(e) Long-term consequences.

Hypothalamic pituitary compartment in PCOS i.e.

Increased pulse frequency of GnRH leads to increased pulse frequency of LH. Leptin (a peptide, secreted by fat cells also by the ovarian follicle), insulin resistance and hyperandrogenemia are responsible for this.
GnRH is preferential to LH rather than FSH.
Increased pulse frequency and amplitude of LH results in tonically elevated level of LH.
Lastly, The LH: FSH ratio is increased.[1]

Sign & Symptoms

Clinical Features of PCOD include:

The patient complains of increasing i.e.

Obesity (abdominal – 50%),
menstrual abnormalities (70%) in the form of oligomenorrhea, either amenorrhea or DUB and infertility.
Presence of hirsutism also acne are the important features (70%).
Virilism is rare.[1]

Acanthosis nigricans i.e.

is characterized by specific skin changes due to insulin resistance. Additionally, The skin is thickened and pigmented (grey brown). Commonly affected sites are nape of the neck, inner thighs, groin also axilla.

Androgen Excess i.e.

Abnormal regulation of the androgen forming enzyme (P450 C 17) is thought to be the main cause for excess production of androgens from the ovaries and adrenals. The principal sources of androgens are i.e.

(A) Ovary

(B) Adrenal

A. Ovary produces excess androgens due to —

(i) stimulation of theca cells by high LH

(ii) P450 C17 enzyme hyperfunction

(iii) defective aromatization of androgens to estrogen

(iv) stimulation of theca cells by IGF-1 (insulin growth factor-1)

B. Adrenals

are stimulated to produce excess androgens by i.e.

(i) stress

(ii) P450 C17 enzyme hyperfunction

(iii) associated high prolactin level (20%).

C. Systemic metabolic alteration

(i) Hyperinsulinemia causes i.e.:

(a) Stimulation of theca cells to produce more androgens.

(b) Insulin results in more free IGF-1. By autocrine action, IGF-1 stimulates theca cells to produce more androgens.

(c) Insulin inhibits hepatic synthesis of SHBG, resulting in more free level of androgens. Features suggestive of insulin resistance are:

BMI > 25 kg/m, Acanthosis nigricans and waist to hip ratio > 0.85.[1]

(ii) Hyperprolactinemia i.e.:

In about 20% cases, there may be mild elevation of prolactin level due to increased pulsitivity of GnRH or due to dopamine deficiency or both. The prolactin further stimulates adrenal androgen production Whatever may be the etiology, the endocrinologic effects of PCOS produce a vicious cycle of events as shown in the scheme–6.

Anovulation i.e.:

Because of low FSH level, follicular growth arrest at different phases of maturation (2–10 mm diameter). The net effect diminish oestradiol and increased inhibin production. Due to elevated LH, there is hypertrophy of theca cells and more androgens are produced either from theca cells or stroma. There defective FSH induce aromatization of androgens to oestrogens.

Follicular microenvironment is therefore more androgenic rather than estrogenic.

Unless there is estrogenic follicular microenvironment, follicular growth, maturation and ovulation cannot occur. There is huge number of atretic follicles that contribute to increased ovarian stroma (hyperthecosis). LH level is tonically elevated Without any surge. LH Surge is essential for ovulation to occur.[1]

Obesity and Insulin Resistance

Obesity (central) recognize as an important contributory factor. Apart from excess production of androgens, obesity also associate with reduced SHBG. It also induces insulin resistance and hyperinsulinemia Which in turn increases the gonadal androgen production.

PCOS Is thought to have a dominant mode of inheritance as about 50% of first-degree relatives have PCOS. Aetiology of insulin resistance unknown. Mutations of the insulin receptor gene in the peripheral target tissues and reduced tyrosine autophosphorylation of the insulin receptor, currently thought to an important cause. Increased central body fat leads to android obesity.

Long-term consequences in a patient suffering from PCOS includes: The excess androgens (mainly androstenedione) either from the ovaries or adrenals peripherally aromatize to estrone (E1). There concomitant diminish SHBG. Cumulative excess unbound E2 and estrone results in a tonic hyperestrogenic state. There is endometrial hyperplasia.[1]

Investigation

Investigation Of PCOD are following:

Sonography — Transvaginal sonography is especially useful in higher-weight person. Ovaries enlarge in volume (> 10 cm). Increased number (> 12) of peripherally arranged cysts (2–9 mm) are Seen.

Serum values i.e.:

LH level elevate and/or the ratio LH: FSH is > 2:1.
Raised level of estradiol and estrone — The estrone level markedly elevate.
SHBG level reduce.
Hyperandrogenism—mainly from the ovary but less from the adrenals. Andro-stenedione raise.
Raised serum testosterone (> 150 ng/dL) and DHEA–S may marginally elevate.
Insulin Resistance (IR): Raised fasting insulin levels > 25 µIU/mL and fasting glucose/insulin ratio < 4.5 suggests IR (50%). Levels of serum insulin response > 300 µIU/mL at 2 hours post glucose (75 gm) load, suggests severe IR.
Laparoscopy — Bilateral polycystic ovaries are

characteristic of PCOS [1]

Treatment

The primary treatments for Polycystic Ovarian Syndrome include: lifestyle changes and medications. [2]

Goals of treatment may be considered under four categories i.e.:

Lowering of insulin resistance levels
Restoration of fertility
Treatment of hirsutismor acne
Restoration of regular menstruation, and prevention of endometrial hyperplasiaand endometrial cancer

In each of these areas, there is considerable debate as to the optimal treatment. One of the major reasons for this is the lack of large-scale clinical trials comparing different treatments. Smaller trials tend to be less reliable and hence may produce conflicting results. General interventions that help to reduce weight or insulin resistance can be beneficial for all these aims, because they address what is believed to be the underlying cause.

As Polycystic Ovarian Syndrome appears to cause significant emotional distress, appropriate support may be useful. [2]

Medications

Medications for PCOS include

[1] Oral contraceptives i.e.

: The oral contraceptives increase sex hormone binding globulin production, which increases binding of free testosterone. This reduces the symptoms of hirsutism caused by high testosterone and regulates return to normal menstrual periods.

[2] Metformin i.e.

is a medication commonly used in type 2 diabetes mellitus to reduce insulin resistance, and is used off label (in the UK, US, AU also EU) to treat insulin resistance seen in PCOS. In many cases, metformin also supports ovarian function and return to normal ovulation.

[3] Spironolactone i.e.

can be used for its antiandrogenic effects, and the topical cream eflornithine can be used to reduce facial hair. A newer insulin resistance medication class, the thiazolidinediones (glitazones), have shown equivalent efficacy to metformin, but metformin has a more favorable side effect profile.

It can be difficult to become pregnant with PCOS because it causes irregular ovulation. Medications to induce fertility when trying to conceive include the ovulation inducer clomiphene or pulsatile leuprorelin. Metformin improves the efficacy of fertility treatment when used in combination with clomiphene. Evidence from randomized controlled trials suggests that in terms of live birth, metformin may be better than placebo, and metformin plus clomiphene may be better than clomiphene alone, but that in both cases women may be more likely to experience gastrointestinal side effects with metformin.

Metformin

is thought to be safe to use during pregnancy (pregnancy category B in the US). A review in 2014 concluded that the use of metformin does not increase the risk of major birth defects in women treated with metformin during the first trimester. Liraglutide may reduce weight and waist circumference more than other medications.[2]

Homeopathic Treatment

Homoeopathic Medicine:

Apis Mellifica [Apis.]

Few remedies cause as many ovarian symptoms as Apis. It has an active congestion of the right ovary going on to ovaritis, with soreness in the inguinal region, burning, stinging and tumefaction. Ovarian cysts in their incipiency have been arrested by this remedy; here one of the indicating features is numbness down the thigh. It has also proved useful in affections of the left ovary. Tightness of the chest may also be present, with the occurrence of a reflex cough and urging to urinate. Mercurius corrosivus. Hughes prefers this remedy in ovarian neuralgia. Peritoneal complications also indicate it. Bovista has also cured ovarian tumors.[3]

Arsenicum. [Ars]

Burning tensive pains in the ovaries, especially in the right. Ovaritis relieved by hot applications. Patient thirsty, irritable and restless. Colocynth. Ovarian colic; griping pains, relieved by bending double; stitching pains deep in right ovarian region. It is also a useful remedy, according to Southwick, in ovaritis of left ovary with colicky pains. A dropsical condition may be present. Hamamelis. Ovaritis and ovarian neuralgia. Ludlam praises this remedy in the sub-

acute form of gonorrhoeal ovaritis; it allays the pain and averts the menstrual derangement. Ovaritis after a blow. There is agonizing soreness all over the abdomen. An external application of hot extract of Hamamelis acts marvelously in subduing the distress and pain consequent to ovaritis. Iodine. Either Congestion or dropsy of the right ovary. Dwindling of the mammae; dull, pressing, wedge-like pain, extending from right ovary to uterus like a plug, worse during menstruation. Thuja. Left-sided ovaritis, with suspicion of veneral taint, calls for Thuja. Grumbling pains in the ovaries all the time, with mental irritability, call for Thuja. Podophyllum has a pain in the right ovary, running down the thigh of that side. Numbness may be an attending symptom.[3]

Belladonna. [Bell]

As this remedy is one particularly adapted to glandular growths it is especially useful in acute ovaritis, and more so if the peritoneum be involved. The pains are clutching and throbbing, worse especially on the right side, the slightest jar is painful, and the patient is extremely sensitive. The symptoms appear suddenly; flushed face and other Belladonna symptoms are present. Platinum. Ovaries sensitive, burning pains in them, bearing down, chronic ovarian irritation with sexual excitement. Much ovarian induration is present. Palladium. Swelling and induration of right ovary. In detail, It lacks the mental symptoms of Platinum, such as mental egotism and excitement. Aurum. Ovarian induration. Lilium. Ovarian neuralgias. Burning pains from ovary up into abdomen and down into thighs, shooting pains from left ovary across the pubes, or up to the mammary gland. Staphisagria. Very useful in ovarian irritation in nervous, irritable women. Hypochondriacal mood.

Lachesis. [Lach]

Pain in left ovary relieved by a discharge from the uterus; can bear nothing heavy on region. Hughes and Guernsey seem to think that Lachesis acts even more prominently on the right ovary; others believe the opposite, the tendency of affections being, however, to move from the left toward the right side. Suppuration and chronic enlargements of ovary may call for Lachesis. Zincum. Boring in the left ovary relieved by the flow, somewhat better from pressure; fidgety feet. Graphites. Swelling and induration of the left ovary; also pains in the right ovarian region with delayed scanty menses. Argentum metallicum. Bruised pain in left ovary and sensation as if ovary were growing large. Naja. Violent crampy pain in left ovary. Dr. Hughes valued it in obscure ovarian pains not inflammatory in nature. [3]

Sepia. [Sep]

Sepia is a remedy acting especially on the female organs and is a most valuable one; it produces in its proving venous congestion, which accounts for many of its symptoms. The general symptoms in a case calling for Sepia are of the utmost importance. Thus, we have characteristically the weakness and want of tone, in the whole system, the yellow complexion, the yellow saddle over the nose, the sunken dark-ringed eyes, the relief fro violent motion, due probably to the toning up of the venous system by such, and the amelioration in the middle of the day. These are all ground characteristics of the remedy; when they are present the other symptoms will found to correspond with the drug most beautifully. Besides this, The menstruation of Sepia may of almost any combination, late and scanty being the most frequent.

Other symptoms

They may early and scanty or early and profuse – discolorations of the skin attending menstruation are characteristic; additionally, the flow is apt to dark, the menses precede by aching in the abdomen and by colicky pains. Amenorrhea in those of distinct Sepia temperament where there is extreme sensitiveness to all impression. The leucorrhea of Sepia is yellow – green in color and somewhat offensive. Lastly, It may be milky; it is worse before the menses and is accompanied by bearing down.

On the uterus itself Sepia exerts a decided action; the uterus found to enlarge and the cervix indurate. Thus, Sepia becomes a useful remedy in displacements, especially prolapsus or retroversion’s. There is irritability of the bladder and leucorrhea. Dunham praised it highly here. There is often present a sensation as if the womb clutch and suddenly released. Bearing down pains are grandly characteristic of Sepia; the patient feels as if everything would protrude from the vulva and this sensation relieve by sitting with the limbs crossed. [3]

Diet & Regimen

Where Polycystic Ovarian Syndrome associate with higher-weight person, successful weight loss is the most effective method of restoring normal ovulation/menstruation. The American Association of Clinical Endocrinologists guidelines recommend a goal of achieving 5 to 15% weight loss or more, which improves insulin resistance also all hormonal disorders. However, many women find it very difficult to achieve and sustain significant weight loss.

A scientific review in 2013 found similar decreases in weight and body composition also improvements in pregnancy rate, menstrual regularity, ovulation, hyperandrogenism, insulin resistance, lipids, and quality of life to occur with weight loss independent of diet composition. Still, a low GI diet, in which a significant part of total carbohydrates are obtained from fruit, vegetables, and whole-grain sources, has resulted in greater menstrual regularity than a macronutrient-matched healthy diet.

Vitamin D deficiency

Vitamin D deficiency may play some role in the development of the metabolic syndrome, so treatment of any such deficiency is indicated. However, a systematic review of 2015 found no evidence that vitamin D supplementation reduced or mitigated metabolic and hormonal dysregulations in Polycystic Ovarian Syndrome. As of 2012, interventions using dietary supplements to correct metabolic deficiencies in people with PCOS had been tested in small, uncontrolled and nonrandomized clinical trials; the resulting data is insufficient to recommend their use.[2]