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Standards of Care Ages 10+ [2023 Conference Video]

In this 1-hour and 25-minute video, Dr. Diane Stafford discusses standards of care for people with Prader-Willi syndrome from age 10 to adulthood.

In this one hour and 25-minute video, Dr. Diane Stafford, Endocrinologist at Stanford University School of Medicine, provides an overview of care for people with PWS over age 10 including medical needs, currently available medications, supplements, labs, and sex hormones.

Click below to watch the video. If you're short on time, scroll down for timestamps to find the portions you're most interested in.


Presentation Summary With Timestamps

0:01 Diane Stafford presents 2023 Conference-Standards of Care Ages 10+ 

0:08 Introduction of Dr. Stafford by Amber Robertson

  • Overview of care for people with PWS, across the age continuum, including 
    • Current medical needs
    • Medications
    • Supplements
    • Behavior management

0:33 Introducing Dr. Diane Stafford

  • Clinical Professor of Pediatrics at Stanford University’s School of Medicine and the Division of Pediatric Endocrinology.
  • She’s been caring for patients with PWS for more than 20 years, both at Stanford and Boston Children’s Hospital.
  • Dr. Stafford disclosed that she is one of the Principal Investigators (PI) for the AR Therapeutics study, soon to be a PI for an Acadia Pharmaceutical study, and a co-PI for Solano Therapeutics. She will discuss off-label use of medications in this presentation.

2:30 Objectives of the Presentation

  • Understand the effects of growth hormone therapy in growing children and also in those who have completed their longitudinal growth
  • Understand the variations in the timing of puberty in those with PWS
  • Recognize the possible need for hormone supplementation to gain a better understanding of the possible effects of anti-obesity medications in PWS
  • Recognize the need for routine monitoring for medical issues associated with older children with PWS 

3:12 PWS in Preadolescence and Adolescence

  • Prior to the use of growth hormone, the average adult height in males with PWS was about 155 cms and 147 in females.
  • This is significantly smaller than the typical population.
  • It is important to understand how growth hormone impacts growth.
  • Throughout this period, children with PWS can have either normal or early adrenarche, which is the development of body hair and body odor.
  • They can also have delayed or absent puberty.
  • They can have continued difficulties with obesity if it started earlier on, and even if they are not obese, there is an increased risk of complications related to obesity, including type 2 Diabetes and obstructive sleep apnea.
  • Other factors are behavioral issues around food and issues of transition to independent living.

4:11 Benefits of Growth Hormone

  • In most people, growth hormone will improve longitudinal growth.
  • In people with PWS, growth hormone will also improve body composition, creating higher muscle mass, lower fat mass, and increased energy and physical activity.
  • Some of that goes along with an increase in muscle mass. They tire less easily and are able to do more things to improve strength, agility, endurance, and respiratory muscle.
  • All of this allows people to have a better quality of life by getting exercise with being less tired.
  • Growth hormone in adolescence works in concert with sex steroids.
  • They work in tandem to result in that pubertal growth spurt that many people experience.
  • In children this age, IGF-1 levels are one of the things used to monitor growth hormone therapy; it’s important to know where someone is in puberty to adjust dosing.
  • A prepubertal 13-year-old’s igf-1 level should not be as high as a pubertal 13-year-old.
  • Sex steroids are required for that pubertal growth spurt, making it necessary to assess pubertal status as part of growth monitoring. 
  • Typical age when people head into puberty is around 10 for girls and around 12 and a half for boys. 
  • Understanding where somebody’s skeletal maturity is can also help you evaluate whether they are growing the way they should be.
  • At the moment, growth hormone can only be continued into adulthood in those who have a diagnosis of growth hormone deficiency. 
  • Because many children with PWS have been on growth hormone for a long time, the way to tell if someone is truly growth hormone deficient is to discontinue the growth hormone and retest them to see whether they actually meet criteria for a diagnosis of growth hormone deficiency.
  • There are creative ways to determine whether someone is experiencing hormone deficiency; it is different with every patient.

13:14 Puberty and PWS

  • Explanation of the hypothalamic pituitary gonadal axis.
    • Two sets of cell types in the hypothalamus: kisspeptin neurons, which activate GnRH neurons. 
    • At puberty, there is a pulse of GnR that starts to be produced to stimulate the pituitary gland to produce FSH and LH, which are the hormones that regulate puberty. 
    • Then that goes to the gonads (testes or ovary) and causes production of testosterone and estradiol and gives you secondary sexual characteristics.
  • At the same time, we also have the hypothalamic pituitary adrenal axis. That is also under the control of the pituitary, secreting a hormone called ACTH, which then dries the adrenal glands, which sit above the kidneys to produce what are referred to as androgens: androstenedione, DHEA, estrone).
  • Puberty is two separate processes.
    • In women, the hypothalamic pituitary adrenal axis produces the androgens that in women are the majority cause for body hair and body odor in women and girls.
    • There’s also androgen production in men in puberty when men start to produce lots of testosterone from the testes.
    • For girls, estrogen production from the ovary causes breast development and internal changes like the size of the uterus. 
    • Breast development is the hallmark of puberty in girls; in boys it is the increase in testicular volume.
    • Body odor is androgen driven and not necessarily true puberty.

16:34 Pubarche

  • Pubarche refers to the development of pubic and axillary hair and is driven by productions of androgens from the adrenal gland (premature adrenarche) and typically occurs after 8 years of age.
  • There are reportedly increased incidences of premature adrenarche in patients with PWS. 
  • Studies reveal increased incidence of adrenarche in children with PWS. 
    • Dutch study showed higher levels of DHEAS development in children with PWS.
    • Indicates early activation.
    • Study of Dr. Stafford’s patients at Boston Children’s Hospital showed 50% of males and 64% of females had premature pubarche.
    • 8.8 years was the average age of Tanner 2 pubic hair development for males; 7.3 years was average for females.
  • Parents; When you see pubic hair and body odor development, do not panic. Tell your endocrinologist so they can run the DHE levels to make sure there’s not something else going on other than the natural history that we frequently see in patients with PWS.

20:09 Puberty in PWS

  • Puberty in PWS is characterized by hypogonadism, or insufficient ability to produce testosterone or estrogen by the testes and the ovaries and therefore inability to go through normal pubertal development. 
    • In newborns, this is characterized by cryptorchidism or small labia minora with normal testosterone/estrogen and gonadotropin levels.
    • In adolescents, hypogonadism means delayed puberty, entrance to puberty with lack of progression, or early or precocious puberty.
    • No definitive way for most of these children to know whether or not they’re going to go through puberty spontaneously later on.
  • Endocrinologists normally classify hypogonadism either as hypogonadotropic hypogonadism, meaning the brain is not making the appropriate signals to send to the testes or ovaries, or hypergonadotropic hypogonadism, which means the signals are being sent out but the ovaries and testes are not able to respond.
  • Some children with PWS have combinations of the two, indicating a combination of hypothalamic dysfunction and some primary gonadal dysfunction.
  • A study of 45 girls with PWS showed that most adults with PWS had incomplete sexual development. About 25% of them met the criteria for what we call hypogonadotropic hypogonadism, but there was a combination in some of them. Some reports of spontaneous Menses, and some irregular Menses. 
  • Multiple Potential Causes for Hypogonadism
    • Gene on the long arm of chromosome 15 in primates may play a role in spermatogenesis and may be the cause of testicular dysfunction.
    • Loss of NECDIN gene may result in impaired development of GnRH neurons and contribute to hypogonadotropic hypogonadism.
    • Variations in MKRN3, which is in the PWS-specific region, is associated with variations in the timing of puberty.
    • No reports of spontaneous fertility in males with PWS.
    • A few spontaneous pregnancies in females with PWS.

25:54 Timing of Sex Steroids

  • Decision about when and whether to start sex steroids in those with PWS has to be made on an individual basis.
  • Based on a lack of spontaneous progression into puberty and pattern of growth. 
  • If you’re not in puberty and your growth rate is slowing down but you’re at an age where you normally would go into puberty, you are not likely to grow well unless someone gives you sex steroids.
  • This decision involves discussions with family and sometimes evaluation of bone density over time. 
  • Estrogen and testosterone are important for cardiovascular health and they’re important for building bone density over time, so if you don’t make sufficient testosterone and estrogen, you’re at risk for osteoporosis, osteopenia, lipid abnormalities, and other problems.
  • Dr. Stafford usually starts people on low doses, trying to mimic a normal process where there is a slow increase in either estrogen or testosterone production. 
  • Also seeks to optimize growth. Hormones help you grow but eventually fuse growth plates, so you need to be careful.
  • Also starts slow because of concerns about potential behavioral changes, although there is no specific data on whether or not sex steroids actually cause behavioral change.

27:33 Incomplete Puberty

  • There is an interplay between growth and puberty. 
  • Shows growth charts:
    •  A girl whose growth began to fall off until she started hormone therapy.
    • Early puberty with poor growth spurt.
    • Effect of estrogen treatment. 

29:20 Sex Steroid Replacement

  • For girls, it is estrogen: transdermal patch or a pill.
  • Eventually you have to add progesterone because estrogen builds the uterine lining and progesterone stabilizes that lining. Withdrawal of progesterone allows them to have a normal period.
  • There is nothing magical about having a period. There are ways to make it so that girls with PWS have very limited numbers of periods or no true period, or maybe a little breakthrough bleeding here and there. 
  • This is another conversation to have with your endocrinologist:
    • Is your child capable of handling Menses?
    • Is someone else dealing with activities of daily living for your child so it’s not important what the timing is?
  • For boys, there are a couple of ways that you can give testosterone. The most common is testosterone enanthate or cypionate, which is given either intramuscularly or subcutaneously.
  • If you’re starting at low doses, it’s easy for most people to do an intramuscular injection once a month to start with, gradually increasing doses.
  • There are testosterone gels and creams that can be used, but Dr. Stafford does not use them because of worrying about contact with other people and the potential of spreading testosterone into the rest of the world where it is not supposed to be.
  • Testosterone patches are no longer on the market, but there is an oral testosterone now approved for use in the U.S.
  • Important thing is discussing with your endocrinologist. 
  • It’s not about periods, body hair, or breast development; it’s about bone health and cardiovascular health and other things that are really important in children that are likely to have lower bone mass from low muscle mass. 
  • We don’t want to put them at another disadvantage.

32: 56 Anti-Obesity Medications

  • Most of the medications discussed here are off-label use as anti-obesity drugs, so Dr. Stafford is clear that these are not approved for obesity. 
  • Topiramate:
    • Medication for migraines and seizures with off-label use for binge eating disorder, mood stabilization, and weight loss.
    • Common side effects: fatigue, dizziness, mood changes.
    • Studies in 2019 and 2003 showed trends in decreased BMI and dose-dependent improvement in hyperphagia, demonstrated weight loss and improved mood.
  • Metformin:
    • Classically used in type 2 diabetes for glycemic control without weight gain and possible weight loss.
    • Decreased glucose production in the liver and glucose absorption in the intestine, increased insulin sensitivity.
    • Side effects: abdominal discomfort, diarrhea, nausea, vomiting.
    • 2014 pilot study showed children with PWS had less food-related distress and anxiety, increased satiety but no significant weight loss. 
  • Phenteremine
    • Thought to release norepinephrine in the hypothalamus, reducing hunger.
    • Side effects: dizziness, dry mouth, gastrointestinal symptoms, tachycardia, hypertension, and difficulty sleeping.
    • Currently FDA approved for obesity management in patients 16 years and up.
    • No studies of people with PWS.
  • Glucagon-Like Peptide-1 (SLP-1) Receptor Agonist
    • Stimulates insulin release, inhibits glucagon secretion, slows gastric emptying, and increases satiety after eating.
    • Side effects: primarily gastrointestinal.
    • Liraglutide (daily) and Semaglutide (weekly)
    • FDA approved for obesity management for patients 12 years and up. 
    • Multi-center, placebo-controlled trials showed hyperphagia and drive scores were lower in adolescents treated with liraglutide vs. no treatment. 
    • No significant change in BMI with liraglutide vs. no treatment. 
  • Huge variability in response among people with PWS, so we need further investigation, some kind of large, multi-center trial on the use of these medications in pediatrics generally and PWS specifically.
  • Not all drugs used for obesity are FDA-approved for this indication or in those less than 10-12 years.

41:00 Co-Morbidities: Type 2 Diabetes

  • Data from insurance databases shows that there is a hefty rise of type 2 diabetes among people with PWS. 
  • Significant rate (27%) have type 2 diabetes by mid- to late-20s.
  • There is also an increase in cardiovascular disease; hypertension and hyperlipidemia in younger ages.
  • Increased risk of sleep apnea.

43:17 Need for Multidisciplinary Care

  • Genetics
  • Endocrinology
  • Pulmonary/sleep medicine
  • Gastroenterology/Nutrition
  • Orthopedics
  • Physical Therapy/Occupational Therapy/Speech Therapy
  • Behavioral Medicine/Neuropsychology
  • Neurology
  • Cardiology

44:00 Recommendations for 5-14 Years

  • Evaluation
  • Medical referrals
  • Laboratory evaluation
  • Diagnostics
  • Medications/Supplements

46:01 Continued Monitoring Is Key

  • Pre-adolescents and adolescents with PWS require close monitoring of growth, pubertal status, and obesity and related co-morbidities.
  • Don’t be afraid of puberty; it is a necessity, not because you need breasts or body hair but because bones and cardiovascular health need it.
  • Multidisciplinary care is key to the long-term health for people with PWS.

46:54: Q & A

FPWR Enewsletter

Topics: Parents, Adults, Children 12-18

Susan Hedstrom


Susan Hedstrom is the Executive Director for the Foundation for Prader-Willi Research. Passionate about finding treatments for PWS, Susan joined FPWR in 2009 shortly after her son, Jayden, was diagnosed with Prader-Willi Syndrome. Rather than accepting PWS as it has been defined, Susan has chosen to work with a team of pro-active and tireless individuals to accelerate PWS research in order to change the future of PWS. Inspired by her first FPWR conference and the team of researchers that were working to find answers for the syndrome, she joined the FPWR team in 2010 and led the development of the One SMALL Step walk program. Under Susan’s leadership, over $15 million has been raised for PWS related research.