Metformin or Oral Contraceptives for treatment of Polycystic Ovarian Syndrome in Adolescents: A Meta-analysis

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorder in adolescent and adult women affecting 1 in 15 women worldwide and have important metabolic and reproductive implication.  

The diagnosis of PCOS is challenging specially in adolescent as normal pubertal changes can mimic the signs of PCOS. The Rotterdam criteria are widely in use for diagnosis. These criteria require that patients have at least two of the following conditions: ovulatory dysfunction, androgen excess, and polycystic ovaries. It is also necessary to rule out other causes of androgen excess and ovulatory dysfunction before a diagnosis of PCOS is made. 

The treatment approach varies according to the age of the patient, desire for pregnancy and the presenting symptoms.  

The Endocrine Society guidelines for the treatment of adults with PCOS recommends using oral contraceptive pills (OCPs) to control symptoms of androgen excess, while reserving metformin for cases with impaired glucose tolerance or features of metabolic syndrome.

However, evidence is sparse to support the best first-line medication in adolescents with PCOS.

Investigators Dr. Reem A. Al Khalifah and colleagues of King Saud University in Saudi Arabia published a metaanalysis and systemic review of randomized, controlled trials (RCTs) to evaluate the use of metformin versus OCPs for the treatment of PCOS in adolescents ages 11 to 19 years in the Pediatrics, online April 28.

The team searched the literature through Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials, and gray literature resources, up to January 29, 2015. Only four RCTs met the inclusion and exclusion criteria’s amounting to 170 patients in total. 

It was seen that OCP treatment resulted in improvement in menstrual irregularities with a modest improvement in the acne scores.  On the other hand, metformin improved the BMI, decreased dysglycemia prevalence and improved total cholesterol and low-density lipoprotein levels. Both treatment modalities have a similar effect on hirsutism. 

However, the evidence quality was very low, so "treatment choice should be guided by patient values and preferences, while balancing potential side effects" said Dr. Al Khalifah

But, as PCOS is a spectrum with many girls presenting with obesity and hairiness while others have normal body weight and just have menstrual irregularities. So, depending upon the symptoms, the treatment is tailored according to the patient need, with either OCP or metformin being the first line of treatment. 

Concurrently, the importance of life style modification and statin is also stressed to provide long term cardiac protection in these patients.

References:
http://womenshealth.gov/publications/our-publications/fact-sheet/polycystic-ovary-syndrome.html#b
http://www.ncbi.nlm.nih.gov/pubmed/26280343
http://press.endocrine.org/doi/abs/10.1210/jc.2013-2350

The New Puberty

The New Puberty

The Book" The new puberty"

This article is based on TEDMED talk 2015 in Palm Springs, California by Pediatric endocrinologist Louise Greenspan and her groundbreaking book, -“The New Puberty: How To Navigate Early Development in Today’s Girls”, along with coauthor Julianna Deardorff, a Berkeley professor of Maternal and Child Health and adolescent psychologist.

Just a generation ago, fewer than 5 percent of girls started puberty before the age of 8, today girls are entering puberty at increasingly younger ages with 10% of girls now showing the first signs of puberty before age 8.

Early puberty can lead to eating disorders, depression, substance abuse, early sexual activity and, later in life, breast cancer.

According to Dr. Greenspan, two important culprits responsible are obesity and family stress.

"We used to say that breast development and pubic hair should not start before age 8. What we know now is that 15% of girls at age 7 are showing breast development," Dr Greenspan reported.

According to Biro.F.M  et al in Pediatrics 2013;132:1019-1027 Girls from racial and ethnic groups with the highest rates of obesity are most at risk for early puberty. In that study, black girls showed breast budding at an average age of 8.75 years, Hispanic girls at an average age of 9.25 years, and white and Asian girls at an average age of 9.75 years.

Higher BMI was the strongest predictor of earlier age at breast stage 2 in this study

The relationship between higher BMI and earlier onset of puberty in girls has been noted previously; in 2 large cross-sectional studies, Pediatric Research in Office Settings (PROS) and the National Health and Nutrition Examination Survey (NHANES) III, earlier maturation occurred in those girls with greater BMI and in those with BMI ≥85th percentile.

Body fat makes estrogens, which are the same kind of hormone that are normally released from the ovaries during puberty. When there is more body fat, there are higher levels of estrogen, which leads to breast budding.

In USA the rate of obesity in children aged 6 to 11 years of age increased from 7% in 1980 to nearly 18% in 2012, according to a report from the Centers for Disease Control and Prevention.

And during the same period, the rate of adolescents 12 to 19 years of age who were obese increased from 5% to nearly 21%.

The trend is not just seen in the U.S., it's seen in multiple countries, probably more so countries closer to the equator than countries in the northern latitudes. But major factor is likely to be, certainly in the developing countries, a switch from a more traditional diet to a more Western diet, which results in greater, perhaps better nutrition or perhaps over-nutrition, and that's certainly a factor.

Stress is the second important factor in causing early puberty; other risk factors are early sexual abuse and toxic levels of family arguments and neighborhood violence.

Dr Greenspan says that “Most notably, a girl who grows up without her biological father is twice as likely to get her period before age 12 as a girl who lives with her biological father.”

She does not refute the endocrine-disrupting chemicals commonly found in plastics and pesticides for early puberty, but it is almost impossible to eliminate endocrine-disrupting chemicals from our environment, and there is no single smoking gun, she explained.

These chemicals can mimic hormones in the body, and some mimic hormones that are important regulators of puberty, particularly estrogen. However, more research is needed on humans.

She noted that "a much more effective public health intervention would be to try to tame the obesity epidemic and put some greater social infrastructure in place to buffer children from the stresses of poverty."

The authors offer highly practical strategies that can help prevent and manage early puberty including limiting exposure to certain ingredients in personal care and household products, which foods to eat and which to avoid, and ways to improve a child’s sleep routine to promote healthy biology.

Moreover, the authors—both mothers of young girls—offer parents, teachers, coaches, and caretakers guidance to initiate and continue the conversation about puberty in an age-appropriate way to support girls as they navigate this complex stage of their lives.

References:

http://thedianerehmshow.org/shows/2015-05-06/whats-behind-early-puberty-in-girls

http://www.jpagonline.org/article/S1083-3188%2812%2900092-7/abstract?cc=y

http://pediatrics.aappublications.org/content/132/6/1019.long

http://www.nytimes.com/2015/02/05/opinion/what-causes-girls-to-enter-puberty-early.html?_r=0

Rosenfield RL, Lipton RB, Drum ML. Thelarche, Pubarche, and Menarche Attainment in Children With Normal and Elevated Body Mass Index. PEDIATRICS 2009;123(1): 84–88

http://pediatrics.aappublications.org/content/132/6/1019.long#xref-ref-4-1