POLYCYSTIC OVARIAN SYNDROME (PCOS) OR DISEASE (PCOD)

Ans. is d i.e. Results in post dated pregnancy

Friends, PCOD is an upcoming problem in adolescent OPD and is so an upcoming topic for PGME exams. It is a very simple topic, you need to know few important points which I am summarizing here.

PCOD- At a Glance :

• PCOD/PCOS (i.e. Polycystic ovarian disease / syndrome) was earlier known as Stein Leventhal Syndrome.°
• Basic pathology – Excess androgen production by ovary/adrenals° which interferes with the growth of ovarian follicle.°

So, PCOS is a condition of Androgen Excess° and Chronic Anovulation.°

Clinical diagnosis of PCOD : It should include any two out of the three of the following :

• Oligo menorrhea.
• Clinical and / or biochemical signs of hyperandrogenism.
• Polycystic ovaries (after excluding congenital adrenal hyperplasia, androgen secreting tumor and hyper­prolactinemia.

Ovarian Pathology :

• Ovaries are bilaterally enlarged° (2-5 times N size) (N size of ovary is 3 X 2 X 1 cm)
• Colour – Pearly white
• Capsule – Tunica Albuginea is thickened°
• Theca cell hypertrophy° (Stromal hyperthecosis due to T androgen levels)
• Multiple follicular cysts° (8-10 mm in size) are localized along the surface of ovary giving a “necklace appearance°” on USG.

Clinical feature : Patient age – most commonly seen in young age i.e. between 15 – 25 years. Chief Complaints :

• Oligomenorrhea / amenorrhea / DUB°
• Infertility° (30 % cases)
• Hirsutism°

Obesity (BMI > 30 kg/m²and waist :Hip ratio > 0.88, waist line > 35°)

Others :

–   Acanthosis nigricans       – Thickened and pigmented skin

Commonly affected areas – Nape of neck, Inner thighs and Axilla.

The skin changes are due to insulin resistance.

HAIR-AN syndrome i.e. Hyper Androgenism, Insulin resistance and Acanthosis nigricans is seen in patients of PCOS.

Lab Abnormalities

2:1° • FSH • T LH & insulin leads to Theca cell hypertrophy° and more of androgen production° ( T in testosterone is seen in 70-80% cases and T in DHEAS seen in 25 – 60% cases). • LH is tonically elevated without any surge which also causes Anovulation.° ” align=”left” height=”91″ width=”586″>Other Lab Abnormalities :

• Insulin resistance° : Raised Insulin levels or Abnormal GTT or ratio of Fasting glucose: fasting insulin is <4.5 (therefore T risk of Diabetes mellitus, hypertension, dyslipidemia and cardiovascular disease).
• T serum prolactin levels° (in only 20% cases).
• Abnormal lipid profile (therefore T risk of hypertension and cardiovascular disease).
• Diagnosis : i. USG – Sonographic criteria for PCOD includes :

–  > 12 small cysto (2 to 9 mm in diameter)

–  Increased ovarian volume (> 10 ml)

or both

– The amount of stroma is increased relative to the number of follicles.

Surgery :

Indications :

• Failure of medical therapy.
• In case of Hyperstimulation.
• Use of GnRH analogues is a cost constraint.

Procedure of Choice : Endoscopic cauterization or CO₂ laser vapourisation of the cysts. Laparoscopic ovarian drilling restores ovulation in PCOS patients resistant to clomiphene.

Ans. is c i.e. Luteinizing hormone

• Ratio of LH/FSH in PCOS is > 2:1
• Ratio of Fasting Glucose: Fasting insulin in PCOS < 4.5

Ans. is a i.e. Polycystic ovary

A young woman presenting in the third decade with obesity, oligomenorrhea, infertility and hirsutism leaves no doubt for the diagnosis of PCOS

Ans. is d i.e. All are correct options                 

Symptoms and signs of PCOD :

• Menstrual dysfunction 
• In women with PCOS – Menstrual dysfunction ranges from amenorrhea to oligomenorrhea to episodic menometrorrhagia. Endometrium in PCOD patients can be both thickened/thinned and atrophied depending on the predominance of the hormone.
• Under the influence of unopposed action → Under the influence of Androgens of estrogen (due to anovulation)
• Thickened unstable endometrium →Thin, atrophied endometrium
• Unpredict able bleeding pattern → Amenorrhea/oligomenorrhea (menometrorrhagia)

Hyperandrogenism: It is manifested clinically by

• Hirsutism (i.e. presence of coarse, dark terminal hair distributed in the male pattern).
• Acne (Acne that is persistent or is late in onset) and/or Androgenic alopecia.
• In contrast signs of virilization such as increased muscle mass, deepening of the voice and clitoromegaly are not typical of PCOS. Virilisation reflects much higher androgen levels and should prompt investigation for an androgen producing tumor of ovary or the adrenal gland.

Other endocrine dysfunction :

• Insulin resistance.
• Acanthosis Nigricans – Skin is characterized by thick, gray-brown velvety plaques seen in areas of flexure like the back of the neck, axilla, crease beneath breast, waist, and groin. It occurs due to insulin resistance.
• Impaired glucose tolerance and type 2 diabetes mellitus.
• Dyslipidemia.
• Obesity.
• Obstructive sleep apnea.
• Increased incidence of metabolic syndrome and cardiovascular disease. A metabolic syndrome characterized by insulin resistance, obesity atherogenic dyslipidemia, and hypertension.
• Increased incidence of endometrial hyperplasia and cancer.
• Infertility.
• Increased rate (30 – 50%) of early miscarriage.
• Complications in Pregnancy – Increased risk of – Gestational diabetes

Consequences of PCOS

Short term consequences                                         Long term consequences

• Irregular menses                                          •  Diabetes
• Hirsutism / Acne / Androgenic alopecia           •  Cardiovascular disease
• Infertility                                                     • Endometrial cancer
• Obesity
• Metabolic disturbances
• Abnormal lipid levels / Glucose metabolism

Ans. is D. i.e. A and B both

• It is one of the most common endocrine system disorders that affect women in their reproductive age.
• PCOS occasionally is seen in prepubertal females.
• It is a syndrome manifested by amenorrhea, hirsutism, obesity and enlarged ovaries.
• Affecting  4-12%  of females.
• Familial inheritance is seen in PCOS.

Note: 

Streak ovaries are seen when genetic material is missing either from the long or short arm of the X chromosome or complete X chromosome is missing as in Turner’s syndrome. Streak ovaries are not seen in PCOS patients.

 Ans. is d i.e. Increase prolactin                  

In patients of PCOS :

• Alterations in gonadotropin releasing hromone pulsatality leads to preferential production of LH, as compared to FSH. Also estrogen has a positive feedback on LH and negative feedback on FSH which leads to increease in LH and decrease in FSH such that LH / FSH is > 2.1.
• Now the question arises whether this increase in LH is persistent. Most of the books donot state anything clearly except that there is an increase in the LH pulse amplitude and frequency. So I had to look up in Leon Speroff (which is the BAAP of all problems related to endocrinology and infertility in Gynae).

Leon Speroff specifically mentions :

“In contrast to the characteristic picture of fluctuating hormone levels in the normal cycle, a ‘steady state’ of Gonadotropins and sexsteroids can be depicted in association with persistent anovulation.”

Ans. is A. i.e. Polycystic Ovarian Disease (PCOD)

• Hirsutism is defined as excessive growth of androgen dependant sexual hair or male distribution of hair in a female.
• The most common cause of hirsutism is Polycystic Ovarian Syndrome.                        
• Polycystic ovarian syndrome accounts for 70 – 80% of cases of hirsutism, with idiopathic hirsutism being the second most frequent cause.                                                              

Remember:

• Hirsutism is associated with excess androgen production (either from ovaries or adrenals), so any cause which increases androgens causes hirsutism.
• Most of the testosterone is bound to sex hormone-binding globulin (SHBG) and is considered biologically inactive.
• Testosterone which is not bound to SHBG is considered biologically active, therefore any factor which decreases

Endometrial carcinoma

PolymenorrheaObesity 

High LH, low FSH and low Estradiol

Ans. is D. i.e. Polycystic ovary syndrome

In PCOS FSH:LH = 1:2 OR 1:3 ( Normal FSH<LH)

FSH:LH = 1:2 ( because FSH is ↓ )

If it comes reverse i.e. LH: FSH than it will be 2:1 or 3:1

Ans. is d i.e. PCOD          

• If a patient is having positive progesterone challenge test it means:-
• The uterus is sufficiently primed with estrogen i.e. estrogen production is normal so, hypopituitarism (option “c”) is ruled out.
• Uterus with its endometrial lining is normal i.e. Ashermann syndrome (option “a”) and Endometrial TB (option “b”) ruled out.
• The outflow tract is normal.
• The defect lies in the production of progesterone (as when progesterone is supplemented from outside it results in withdrawal bleeding) and since progesterone is produced mainly by corpus luteum so, the defect is anovulation. The main cause of Anovulation in a case of 2° amenorrhea is a polycystic ovarian disease (option “d”).

Polycystic ovary syndrome

Endometrial carcinoma

– GnRH pulse frequency

– LH over FSH dominance

– Increased ovarian androgen production

– Decreased follicular maturation

All these leads to PCOS.

PCOS and Ghrelin

• Ghrelin is a novel gastric peptide which has orexigenic and adipogenic properties. Ghrelin has been shown to modulate the secretory pattern of pituitary hormones and it may exert direct effect on peripheral organs such as gonads and pancreas.

Signs and symptoms of polycystic ovary syndrome:-

• Hyperandrogenism (acne, hirsutism, alopecia not virilization
• Menstrual disturbance
• Infertility
• Obesity
• Sometimes asymptomatic with polycystic ovaries on ultrasound scan

Serum endocrinology ?

• T Fasting insulin (not routinely measured, insulin resistance or impaired glucose tolerance assessed by G.T.T.)
• T Androgens (testosterone and androstenedione)
• T Leutinizing hormone (LH), usually normal follicle stimulating hormone (FSH)
• T Sex hormone binding globulin (SHBG) results in elevated free androgen index
• T Oestradiol, oestrone
• Mild increase in serum prolactin

Possible late sequale:?

• Diabetes mellitus
• Dyslipedemia
• Hypertension, cardiovascular disease
• Endometrial cancer
• Breast cancer

Management

• Traditionally the management of PCOS has been mainly symptom oriented as no one cause could be attributed to the condition.
• However, with the recent identification of the central role of insulin resistance to the aetiology of PCOS, treatment is now aimed towards measures to improve insulin resistance as these have been shown to improve the regularity of menstrual cycles, ovulation, androgen levels.
• Life style modification and metformin which both improve insulin resistance have therefore been the focus of research.

Life style modification 😕

• Life style modification is very important in the treatment for PCOS as weight loss and exercise show a striking improvement in ovulatory function and hyperandrogenism.

The life style modifications recommended in PCOS are 😕

• Dietary modification
• Moderate exercise
• Cessation of smoking
• Moderate alcohol and caffeine intake

Metformin

• There have been several studies evaluating the effectiveness of metformin in PCOS. In summary, these studies show that although there is clear evidence that metformin improves menstrual cyclicity and ovulation in PCOS, the effects on live birth rates, hirsutism, acne and obesity are unclear.
• Metformin can be offered to all women with anovulatory infertility due to PCOS who have been trying to conceive for a year or more as a first line drug or where elomiphene treatment has failed.
• The optimal period of monotherapy for fertility is unknown. Some tudies have shown a rapid retun to spontaneous ovulation and normal menstrual rhythm within three months of the start of the therapy.
• There is no correlation b/w length of trial and proportion ovulating with metformin alone. It is however recommended that where metformin is used as stand alone first line therapy it is continued for 6-12 months if regular ovulation is documented however if it has not been effective after 3-6 months tit. clomiphene should be added for further 6 months.

Ans. is A. i.e. 1-4 days

LH and FSH are maximum during the preovulatory period. So the best option provided here is 1-4 days.

PCOS is a syndrome manifested by amenorrhea, hirsuitism and obesity associated with enlarged polycystic ovaries. Patients presents with obesity, hirsuitism, oligomenorrhea or amenorrhea and infertility.

Investigations reveals LH:FSH >3:1, reduced level of SHBG and sex hormone binding globulin, elevated levels of androstenedione and serum insulin level, marginally elevated levels of serum testosterone and DHEAS. Transvaginal ultrasonography shows enlarged ovary with peripherally arranged cysts.

Ref: Textbook of Gynecology By DC Dutta, 4th Edition, Pages 285, 405, 421-3

LH and FSH are maximum during pre ovulatory period. So the best option provided here is 8-10 days. Ref: Shaw’s Textbook of Gynaecology, 12th Edition, Page 77 ; The Menstrual Cycle: Physiology, Reproductive Disorders and Infertility By Michel Ferin, Raphael Jewelewicz, Michelle P. Warren, 1993, Page 5 ; Reproductive Endocrinology and Infertility: Integrating Modern Clinical and Laboratory Practice By Douglas T. Carrell, 2010, Page 147

Osteoporosis does not occur as a complication of Polycystic Ovarian Syndrome (PCOS).

Women with PCOS have high level of estrogen, so not at risk of developing osteoporosis, but at risk of endometrial hyperplasia leading to adenocarcinoma and cancer of breast.

Ref: Willaim’s Gynaecology, 1st Edition, Page 385, 391; Novak’s, 14th Edition, Page 1082, 1077; Polycystic Ovary Syndrome By Hamburg, 2nd Edition, Page 191; Polycystic Ovary Syndrome By Dutta, 1st Edition, 2004, Page 18.

Ans. is C. i.e Low Prolactin

Raised serum luteinising hormone (LH) and raised androgens such as testosterone are the endocrine markers of polycystic ovarian syndrome (PCOS).

Ref: Harrison’s Principles of Internal Medicine, 16th Edition, Pages 2204-05; Shaw’s Book of Gynaecology, 13th Edition, Page 353; Textbook of Gynaecology By Dutta, 4th Edition, Pagrs 422-23; Polycystic Ovary Syndrome By Gábor T. Kovács, Robert Norman. 2007, Page 215.

Polycystic ovarian disease (PCOD) is characteristically associated with elevated LH levels, abnormal glucose tolerance and may present with infertility.

Postdated pregnancy has not been mentioned as a sequelle to PCOD.

Ref: Novak’s Gynecology, Pagve 876; Harrison’s Principles of Internal Medicine, 16th Edition, Pages 2204-05; Shaw’s Book of Gynaecology, 13th Edition, Page 353; Textbook of Gynaecology ByDutta, 4th Edition, Pages 422-23; Polycystic Ovary Syndrome By Gábor T. Kovács, Robert Norman, 2007, Page 215.

Women with Cushing syndrome, congenital adrenal hyperplasia, and androgen-secreting adrenal tumors also tend to have high circulating androgen levels and anovulation with polycystic ovaries.

PCOS is a syndrome manifested by amenorrhea, hirsuitism and obesity associated with enlarged polycystic ovaries.

Patients presents with obesity, hirsuitism, oligomenorrhea or amenorrhea and infertility. Investigations reveals LH:FSH >3:1, reduced level of SHBG and sex hormone binding globulin, elevated levels of androstenedione and serum insulin level, marginally elevated levels of serum testosterone and DHEAS. Transvaginal ultrasonography shows enlarged ovary with peripherally arranged cysts.

Ref: Textbook of Gynecology By DC Dutta, 4th Edition, Pages 285, 405, 421-3

Raised serum luteinising hormone (LH) and raised androgens such as testosterone are the endocrine markers of polycystic ovarian syndrome (PCOS).

Ref: Harrison’s Principles of Internal Medicine, 16th Edition, Pages 2204-05; Shaw’s Book of Gynaecology, 13th Edition, Page 353; Textbook of Gynaecology By Dutta, 4th Edition, Pagrs 422-23; Polycystic Ovary Syndrome By Gábor T. Kovács, Robert Norman. 2007, Page 215.

Polycystic ovarian disease (PCOD) is characteristically associated with elevated LH levels, abnormal glucose tolerance and may present with infertility.

Postdated pregnancy has not been mentioned as a sequelle to PCOD.

Ref: Novak’s Gynecology, Pagve 876; Harrison’s Principles of Internal Medicine, 16th Edition, Pages 2204-05; Shaw’s Book of Gynaecology, 13th Edition, Page 353; Textbook of Gynaecology ByDutta, 4th Edition, Pages 422-23; Polycystic Ovary Syndrome By Gábor T. Kovács, Robert Norman, 2007, Page 215.

Ans. is ‘b’ i.e., PCOD

o Continuous administration of GnRH analogues can be used in PCOD.

Ans. D: Decreased testosterone level

Raised: E2 (oestradiol), LH, androgens, testosterone, epiandrostenedione, fasting insulin, prolactin Decreased: FSH, FSH/ LH ratio, sex hormone binding globulin, osetradiol (E2)/ oestrone (El) ratio

Ans. is B i.e. PCOD

USG feature: String of pearls/ Necklace appearance

DIAGNOSTIC CRITERIA – ROTTERDAM CRITERIA (2003)

Any two of the following three criteria should be present to diagnose a patient having PCOD after excluding other etiologies.

1. Ovulatory dysfunction such as oligomenorrhea or amenorrhea.
2. Clinical (hirsutism/acne/alopecia) or biochemical evidence of hyperandrogenism i.e. S. testosterone between 70-150 ng/ dl.
3. Polycystic ovarian morphology on USG scan defined as the presence of 12 or more cysts size: (2-9 mm) ] in any one ovary or both ovaries, with enlarged ovaries I (>10 ml) and other criteria being excluded.

Ans. is B i.e. PCOD

• It is one of the most common endocrine system disorders that affect women in their reproductive age.
• PCOS occasionally is seen in prepubertal females.
• It is a syndrome manifested by amenorrhea, hirsutism, obesity and enlarged ovaries.
• Affecting  4-12%  of females.
• Familial inheritance is seen in PCOS.
• The autosomal dominant mode of inheritance of Gene CYP21 mutation has been found associated.
  CLINICAL FEATURES :
  • Obesity: (BMI >30kg/m2) but PCOD can also occur in thin females.
  • Insulin resistance-hyperinsulinemia
  • Acanthosis nigricans
  • Hyperandrogenemia
  • Hirsutism
  • Anovulation
  • Menstrual Dysfunction
  • Acne and alopecia.
  • Sleep  apnea
  • High-stress levels
  • Skin  tags
  • Infertility
  • High  cholesterol and triglycerides
  • Type II diabetes
  • Pelvic pain
  • Depression and anxiety
    

    HORMONES INCREASED	HORMONES DECREASED
    Androgens (Testosterone, Androstenedione, DHEA, DHEAS)	Follicle-stimulating hormone (FSH)
    Luteinizing hormone (LH > 10 IU/L)	Progesterone (due to anovulation)
    Estrone	Sex hormone-binding globulin
    Total free estrone	HDL & Apoprotein A-l
    Insulin (> 10 m IU/L due to insulin resistance)
    Prolactin (in some patients)
    LDL cholesterol and triglycerides .
    AMH

Ans. is D ‘i.e., Both a and b

• Beside DM, metformin is also useful in polycystic ovarian disease.
• Suppress hepatic gluconeogenesis and glucose output from liver major action.
• Enhance insulin-mediated glucose disposal in muscle and fat (Increased peripheral utilization of glucose) by enhancing GLUT-1 transport from intracellular site to plasma membrane.
• Retard intestinal absorption of glucose.
• Promote peripheral glucose utilization by enhancing anaerobic glycolysis.
• Metformin is the only oral hypoglycemic that reduces macrovascular events in type 2 DM.
• Metformin is one of only two oral antidiabetics in the WHO model list of essential medicines (the other being glibenclamide).

Ans. is ‘B’ i.e., PCOD

GnRH agonists

• Long-acting GnRH (LHRH) agonists cause reversible pharmacological orchiectomy (medical castration) and are used for precocious puberty, prostatic carcinoma, endometriosis, premenopausal breast cancer, uterine leiomyoma, polycystic ovarian disease and to assist induced ovulation.
• GnRH agonists have an action similar to Gonadotropin-releasing hormone, i.e., they increase the secretion of gonadotropins (FSH, LH).
• GnRH agonists increase Gn secretion.
• But after 1-2 weeks they cause desensitization and down-regulation of FSH/LH receptors. (continuous exposure to agonist may cause downregulation of receptors)→ suppression of gonadal function.
• Spermatogenesis/ovulation ceases and testosterone/estrogen levels fall to castration level because the action of Gonadotropins (FSH & LH) is not there (these hormones promote gametogenesis and secretion of gonadal hormones).
• Preparation of superactive GnRH analogs is Buserelin, Goserelin, Leuprolide, Nafarelin, Triptorelin.
• Superactive/Long-acting GnRH is used as a nasal spray or SC injection.
• Cetraria, ganirelix and abarelix are GnRH antagonists. These are used subcutaneously for the treatment of uterine fibroid & endometriosis and controlled ovarian stimulation in in-vitro fertilization.
• GnRH agonists, as well as GnRH antagonists, can cause hot flushes, loss of libido and osteoporosis as adverse effects.