Jumpstarting Puberty for Optimal Biopsychosocial Outcomes in Girls

Written by W. Todd Penberthy
A complete hormone panel, autoimmune test, and karyotype testing should be done before starting hormone replacement therapy (HRT) and the treatment must be individualized with psychosocial considerations,1 said Catherine Gordon, MD, MSc, professor of adolescent medicine and pediatric endocrinology at Cincinnati Children’s Hospital, in Ohio, speaking at ENDO 2017, the Endocrine Society's 99th Annual Meeting and Expo, in Orlando, Florida.

If and When to Induce Puberty in Girls?

Pubertal induction with hormone replacement therapy (HRT) started at age 12 can prevent otherwise lifelong effects of delayed puberty, said Dr. Gordon.
 
Since puberty is one of the most emotionally charged phases of life for most girls, puberty stalled due to an estrogen deficiency may have profound life-long effects on physiological development, including bone mass, height, and breast development.1
 
Girls experiencing estrogen deficiency typically present with decreased functionality due to substandard energy and moodiness. Fortunately, many of these individuals are identifiable by the age of 12 and can be treated successfully with HRT, she said.
 
“However, patients can have signs of ovarian insufficiency at any point,” Dr. Gordon told EndocrineWeb. “Sometimes the ovaries start to malfunction before puberty has started (so puberty never starts) and other girls develop breasts which is the first sign of puberty—and then development stops.”
 
“The only time that we would initiate estrogen therapy before age 12 would be if a girl had started development on the early side (eg, age 9), and then further development stopped, and if at the same time she had signs of estrogen deficiency (eg, fatigue, hot flashes, etc),” said Dr. Gordon.
 

Addressing “Am I Normal?”

With respect to menses onset and breast development, teens are always wondering if they are maturing just like their peers.  While their concern is always, "am I normal?", pediatric endocrinologists are faced with assuring their physiological status (ie, stature and growth rates) falls within developmentally appropriate ranges.
 
More critical for clinicians is, "to delicately provide HRT, trying our best to determine what mother nature should be doing in terms of hormones affects on brain development and cardiovascular tissues,” said Dr. Gordon.
 

When and for Whom to Initiate HRT?

Adolescents with primary ovarian insufficiency (POI) are the predominant candidates to receive HRT, according to Dr. Gordon.
 
The introduction of hormones1 should follow a step-wise process:
Physicians will want to get a thorough medical history at presentation, with input from both the patient and her parent(s) in order to establish a baseline in mood, physiological parameters, and expectations. Getting to know the family is imperative as may be necessary to talk with the parents to get complete information, as the process progresses such as: Is she experiencing hot flashes, amenorrhea, dysmenorrhea, insomnia, or mood changes? These are all important questions, according to Dr. Gordon., and pay close attention to height potential at presentation. 
 

Advantages of the Estrogen Patch 

Introducing estrogen has therapeutic benefits for blood pressure, lipids, and inflammatory markers, which means adherence is critical.1 Find out how the patient feels about the patch versus a pill. 
 
“Sometimes a 13 or 14 year old can already know and be afraid that they are not going to be able to have children. So this is where working with a social worker can be very helpful for pediatric endocrinologists,” said Dr. Gordon. 
 
At our center, we have a 3-pronged approach that addresses medical and psychosocial concerns with a team consisting of a social worker, and gynecologist working with the pediatric endocrinologist,1 she said.
 
Encouraging hormone administration via a transdermal patch is preferred for willing adolescents as they don’t need to remember to take the pill, and assures better consistency in management of lipids, blood pressure, and inflammatory markers, while not increasing VTE risk or decreasing IGF1.1
 
Estradiol patch dosing must be started a very low dose (~4µg/d) and increased gradually to 100µg/d avoid side effects,1 said Dr. Gordon. 
 
To start HRT using the patch, begin with an initial dose of 1/6th of a 25 µg patch at night, increasing the dose to 1/3rd, then 1/2, then 37 µg/d, 50 µg/d, until achieving the full dose of 100 µg/d, she said. Progestin can be added to avoid premenstrual syndrome.1 Keep in mind that an excessively high initial dose of estrogen is likely to cause headaches, nausea, and mood instability.  
 

Achieving Peak Bone Mass

Depending upon the bone density at presentation, Dual-energy X-ray absorptiometry (DXA) scans are recommended for patients that have experienced amenorrhea for 6 months.1 A daily multivitamin with 600 IU of vitamin D, or higher if vitamin D as is low (25 OHD < 20ng/mL) to assist in approaching peak bone mass, according to Dr. Gordon.
 
Newer estrogen combinations that include either dehydroepiandrosterone (DHEA), recombinant human insulin-like growth factor (rhIGF-1), or testosterone, may offer additional benefit for bone development in cases in which the adolescent is at risk for or diagnosed with anorexia nervosa (disordered eating) or is experiencing amenorrhea, she said. 
 
Pubertal induction needs to be highly individualized so it is imperative to obtain a hormone panel before initiating HRT.1
 
“I can’t underscore enough the importance of doing the autoimmune tests,“ as well, said Dr. Gordon, and always get a karyotype to check for Fragile X, galactosemia, and others. 
 
She mentioned other important checks and balances,1 such as: after 6 months of amenorrhea, order a DXA scan and pelvic ultrasound and be sure the DXA technologist corrects the D score for the adolescent’s bone age; monitor height, growth velocity, blood pressure, lipids, liver function, and psychosocial status. 
 

Sources

 

Gordon C. Optimizing Pubertal Induction and Cyclicity in Girls. Presented at: Endo 2017 on April 1, 2017; Orlando, Florida.​​