PCOS in Adolescents

Journal Watch:

Polycystic ovary syndrome in adolescence - a therapeutic conundrum
Homburg and Lambalk
Hum. Reprod. (2004) 19 (5): 1039-1042.
doi: 10.1093/humrep/deh207
First published online: March 11, 2004

• The early diagnostic signs of PCOS are often attributed to the physiological changes of adolescence, thereby delaying diagnosis. Early diagnosis would help prevent and control the sequelae of PCOS.
• Adoloscents with oligomenorrhoea (infrequent periods) that does not correct itself & persists 2 years after menarche (onset of menstrual cycles) should be investigated for early features of PCOS.
• Acne is common in teenagers; when very severe/persistent/late onset, one must investigate for PCOS.
• Premature pubarche (appearance of pubic hair) is considered the earliest recognized sign of PCOS.
• Elevated levels of Insulin and DHEAS with premature pubarche indicate a High Risk for PCOS.
• PCOS in adolescents is a clinical diagnosis as biochemical parameters are often normal. Lab results thus should not be solely relied upon and should be used to rule out other conditions.
• In obese adolescents, the early presence of Insulin Resistance and Impaired Glucose Tolerance indicate a need for lifestyle interventions. Fasting Lipids and two hour glucose challenge should be tested periodically in these individuals. Weight loss is a primary & essential part of their treatment plan.
• A fasting glucose to insulin ratio of less than 7 indicates Insulin Resistance in adolescents.
• Antiandrogens are excellent for the management of acne and hirsutism when used with cyclical OCPs.
• Results are seen after 4-9 months of treatment in hirsutism and after 3-5 months in acne patients.
• With combined use of OCPs and antiandrogens about 60% patients could be expected to be acne free in six months and about 95% to be acne free in twelve months of starting treatment.
• A longer treatment with antiandrogens, while managing adverse effects, may reduce risk of relapse.
• Untreated PCOS is usually a progressive syndrome at least until the age of forty years.
• The use of cyclical Ethinyl Estradiol with Cyproterone Acetate may put the progression of PCOS on hold and also increase the chances of conception when the medication is stopped.
• Central obesity exacerbates Insulin Resistance.
• The first line of treatment for PCOS and especially in adolescents, is weight loss, if overweight/obese.
• Maintenance of a normal body weight is as effective as Metformin for treating Hyperinsulinemia.

Management of Hirsutism

Journal Watch:


Management of hirsutism

Alsantali and Shapiro

Skin Therapy Letter

2009 Sep;14(7):1-3.
Highlights:

•  More than 70% of hirsutism is caused by PCOS
• Early morning plasma total testosterone level and free testosterone level need to be evaluated in cases of mild to moderate hirsutism OR any severity of hirsutism with certain listed key clinical features.
•  Topical Eflornithine 13.9% is FDA approved for reduction of unwanted facial hair in women but takes six to eight weeks to start showing any results. It may cause itching and dryness in some women.
• Oral Contraceptive Pills are the mainstay of treatment. Commonly used brand names are Diane (Ethinyl Estradiol + 2 mg Cyproterone Acetate) and Yasmin (Ethinyl Estradiol + 3 mg Drospirenone).
• Flutamide and Finasteride have some effect but are not first line treatments for hirsutism.
• Insulin Sensitizers like Metformin give limited or no improvement in hirsutism and are not indicated.
• GnRH agonists give good reduction of ovarian androgens. But they are expensive, require injections, therapy with estrogen and show no significant benefit over OCPs or anti andogens. 
• GnRH agonists and Glucocorticoids are not widely used in the management of hirsutism and their use is limited to certain special casesor those not responding to therapy with the other classes of drugs.

PCOS and Acne

Journal Watch:

Polycystic Ovary Syndrome and Acne
Sandy S. Chuan, MD and R. Jeffrey Chang, MD
Skin Therapy Letter. 2010;15(10):1-4.

Highlights:

• Women with PCOS have an excess of androgens due to which they may develop dermatological concerns such as hirsutism, acne vulgaris, and androgenic alopecia. 
• Acne occurs in 10 to 34% of women with PCOS. Most women with PCOS have facial acne lesions, while 50% have additional acne on the chest, upper back and neck.
• Women with PCOS with acne usually have elevated levels of circulating androgens. However, the severity of acne does not directly correlate to the levels of these androgens in the blood.
• However, some studies show that the severity of acne in PCOS patients may be directly correlated to the levels of DHEA-S in blood and inversely related to the level of SHBG produced in the liver.
• Many women with PCOS who have hirsutism do not have acne and vice versa. This may be due to the differential activity of the two isoforms of the ezyme 5alpha reductase and local androgen levels.
• For women with PCOS and acne, OCPs (oral contraceptive pills) are the mainstay of treatment.
• A Cochrane review noted that treatment of acne with OCPs effectively lowered the lesion count of acne, severity of acne as well as improved the self assessment by the patient.
• In women with PCOS who have acne, OCPs are the first line of treatment unless otherwise indicated.
• If there is no improvement or insufficient improvement, one may add oral Antiandrogens to OCPs.
• Insulin sensitizing drugs like Metformin are known to benefit patients with PCOS by reducing insulin levels. However, they are not recommended for treating either acne or hirsutism alone in such patients.
• The combination of OCPs and Flutamide works better than Flutamide alone for PCOS with acne.
• Finasteride is more effective as a treatment for hirsutism in PCOS than for PCOS with acne alone.
• Spironolactone works as an antiandrogen and also reduces sebum production, thereby improving acne. Spironolactone in PCOS is used at a lower dose for treating acne than for hirsutism. It may be added to the treatment plan of women on OCPs showing inadequate improvement with OCPs alone.
• For patients with PCOS, hirsutism and acne, being treated with OCPs showing inadequate improvement, it might be better to add Flutamide than Spironolactone to ongoing OCP treatment.
• Spironolactone is teratogenic thus is always given in conjunction with OCPs to avoid unplanned pregnancy. The patient must also stop Spironolactone three months before trying to conceive.

Treatment of hirsutism in PCOS

Journal Watch:

THERAPY OF ENDOCRINE DISEASE: 

Treatment of hirsutism in the polycystic ovary syndrome
Renato Pasquali and Alessandra Gambineri
Published online before print November 22, 2013, doi:10.1530/EJE-13-0585Eur J Endocrinol February 1, 2014170 R75-R90Highlights of an excellent review on the subject, recently accepted for publication:

• Hirsutism must be distinguished from Hypertrichosis and Virilisation
• Hirsutism (excess terminal hair in androgen sensitive area of the female body: upper lip, chin, chest, back, abdomen, arms& thighs) occurs in 3-15% of the normal population but occurs in almost 75% of women with PCOS. It is also more severe in obese women, especially those with abdominal fat.
• Women with a sudden, recent and rapid onset of hirsutism at any age must be evaluated to rule out tumors or drug interference. Slow onset mild hirsutism around puberty is usually due to PCOS.
• Androgens are also synthesized within the hair follicle. Thus, levels of androgens circulating in the blood correlates only partially but significantly with the modified Ferriman-Gallway score (mFG). However, it is important to test the circulating androgen levels in all women with hirsutism.
• The management of hirsutism depends, among other factors, on the age and severity and on how much it bothers the woman. Treatment may vary widely in different groups and may include lifestyle modifications, weight management, bariatric surgery, cosmetic and pharmacological intervention (topical and sytemic drugs.)
• A recent Cochrane review noted that Alexandrite and Diode Lasers may cause almost 50% reduction in unwanted hair in a few months of treatment. These work by exerting a folliculocitic effect.
• Topical Eflornithine may provide additional benefit in some women though it does not remove hair.
• Oral medication may include various Antiandrogens, Estrogen-Progestin compounds, Metformin etc.
• In morbidly obese women, when other conditions for bariatric surgery are met, such a surgery may give a significant weight reduction and thereby may resolve the phenotype of PCOS.
• Exercise and lifestyle interventions along with weight loss play an important role in the treatment of hirsutism. The presence of obesity reduces the clinical efficacy of various medications.
• The article explores the evidence backing the selection of oral medication in various groups of women with hirsutism, depending on their age, weight, stage in reproductive cycle, whether planning a pregnancy or not and other metabolic factors such as glucose intolerance and diabetes mellitus.   

Ultrasound studies and PCOS

Example: "My daughter has severe acne. She has also recently gained a lot of weight. Why is the dermatologist asking her to get an ultrasound done? What is the connection? I am worried about this."

Discussion:
The girl above has severe acne and a history of weight gain. These are two common symptoms in a person with Polycystic Ovarian Syndrome or PCOS. It is likely that the ultrasound was recommended to screen for PCOS, wherein the ovaries may show multiple small cysts. However, not all patients with these symptoms have PCOS and not all patients with PCOS show these symptoms or have any changes in the ultrasound. Thus the ultrasound is only part of the PCOS work up and must be correlated clinically with history and examination.

Multiple small cysts seen in the ovary around a dense pattern, called the 'String or Pearls' sign which indicates the presence of PCOS in the individual. It however is only one sign of PCOS and does not dictate all the symptoms of the person.

One must not be unduly concerned about being asked to undergo an ultrasound and should discuss the above with the dermatologist/treating physician. If the doctor is considering PCOS as a diagnosis they may also recommend various blood tests and a detailed menstrual history along with the ultrasound to gain a complete picture. With a complete diagnosis, it would be possible to offer a far superior and more effective treatment for all concerns.

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ULTRASOUND CRITERIA FOR MAKING A DIAGNOSIS OF PCOS:

PCOS does not have a single definitive picture but occurs as a cluster of symptoms and signs. Women with the condition may have all/some/none of the symptoms associated with PCOS with or without ultrasound evidence of PCOS. Several studies have highlighted that the criteria used to establish the diagnosis of PCOS remain controversial. The revised diagnostic criteria proposed in 2003 at the Rotterdam European Society of Human Reproduction and Embryology/American Society of Reproductive Medicine consensus workshop stated ultrasound polycystic ovarian morphology (PCOM) be necessary to establish the diagnosis of PCOS. A recent study funded by Cornell University noted that the existing Rotterdam criteria for diagnosis of PCOS using did not adequately and specifically cater to all groups of women with PCOS.

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Bibliography:

1. Hum Reprod. 2013 May;28(5):1361-8. doi: 10.1093/humrep/det062. Epub 2013 Mar 15. Updated ultrasound criteria for polycystic ovary syndrome: reliable thresholds for elevated follicle population and ovarian volume. Lujan ME, Jarrett BY, Brooks ED, Reines JK, Peppin AK, Muhn N, Haider E, Pierson RA, Chizen DR.

2. Semin Reprod Med. 2008 May;26(3):241-51. doi: 10.1055/s-2008-1076143. Polycystic ovary syndrome: the controversy of diagnosis by ultrasound. Porter MB.

3. J Obstet Gynaecol Can. 2008 August; 30(8): 671–679. Diagnostic Criteria for Polycystic Ovary Syndrome: Pitfalls and Controversies. Marla E. Lujan, Donna R. Chizen, Roger A. Pierson

4. J Hum Reprod Sci. 2013 Jul;6(3):194-200. doi: 10.4103/0974-1208.121422. Anthropometric, clinical, and metabolic comparisons of the four Rotterdam PCOS phenotypes: A prospective study of PCOS women. Kar S.