Hormone Treatment Therapy

Introduction

Hormone treatment therapy has become a reliable method of improving the development of patients with Turner Syndrome. They can undergo either growth hormone therapy or estrogen replacement therapy. However, both are recommended treatments to ensure that patients with TS age healthily. If you or a loved one were recently diagnosed with TS. It is advised to start hormone treatment therapy as soon as possible, so that the effects of TS can be reduced. Hormone treatment therapy can be expensive, ranging from $10,000 to $60,000 a year for growth hormone treatment alone. However, the Turner Syndrome clinical practice guidelines indicate that due to the medical necessity of hormone treatment in Turner Syndrome, patients who are un-insured or unable to afford the financial costs are entitled to compensation. For more information about reimbursement programs, click here: https://turnersyndromefoundation.org/turner_syndrome/resources/reimburse-assist/

How Can I Prepare My Child for Hormone Therapy?

 When talking about the treatment with your child, always remain calm and patient; yet firm. Explain to your child that this is medicine that must be given to help them grow. For any questions, concerns, or comments you may have, talk with your doctor or case manager. If you can’t do the injections alone, having a support system (friends, neighbors, etc.) is helpful. Ensuring your child has a nighttime routine can also help to make things run more smoothly. To get your family involved in this new process, have them measure their own heights every so often with your child that is taking growth hormone so she can realize she is growing just like your family. For more information about growth treatment strategies, follow the link: https://turnersyndromefoundation.org/turner-syndrome-across-the-lifespan/growth/growth-treatment-strategies/

Growth Hormone Therapy:

Growth Hormone therapy is meant to help patients with TS improve their height. The average height of an adult woman with Turner Syndrome is 4 ft. 8 in, and 95% of all individuals with TS are affected by short stature. It is the most consistent and readily recognizable clinical feature of TS. The overall growth restriction is characterized by the slow growth during infancy, and the delayed onset of growth during childhood, along with a lack of a pubertal growth spurt. Since the rate of growth is reduced, the overall height of a TS patient is on average about 8 inches less than the average female. 

How Does Growth Hormone Therapy Work?

The treatment is given as an injection every night, with an adjusted dose every 3-6 months that is regularly monitored by a physician to ensure that it is functioning properly. Since growth hormones are naturally secreted at night, the injection of synthetic growth hormone is intended to closely mimic the process of normal secretion. If an injection is missed, do not take an additional dose the next day to compensate. This can reduce the potency of the medication. Instead, continue with the normal daily dose again that night. The growth hormone medication, known as somatropin, is a synthetic protein that helps with bone and muscle growth. There are a variety of marketed products that utilize somatropin as the primary ingredient for injections. For more information, consult your healthcare provider to find which medication would be the right choice for you. 

How Will Growth Hormone Therapy Help?

The goal is to increase the rate of childhood growth, or what is known as the “height velocity”, rather than to adjust the final height of the patient. A child with TS will usually take growth hormone until their height velocity decreases to about 2 cm with a bone age of at least 13-14 years. Bone age does not necessarily correlate with the age of the patient, which means it is possible for a child to take growth hormone beyond 14 years of age. There are additional factors that can affect adult height, which can vary based on the individual, whether it be genetics, ethnicity, or general health. The final height for an adult patient will improve if treatment is started at a young age, after the recognizable features of slow growth are caught early.

 When Should Growth Hormone Therapy Start?

It is recommended that GH therapy start as soon as a patient is diagnosed with TS. However, the preferred age to initiate treatment is between 4-6 years of age, and preferably before 12-13 years old to get the most effective level of growth. Additionally, research conducted by The Toddler Study indicates that treatment initiated earlier can have even more substantial effects on childhood growth. It’s important that you seek medical advice for concerns regarding when it is appropriate to begin treatment, and always consider what is comfortable for you and your loved one. 

Side Effects/Risks for Growth Hormone Treatment

An occasional side effect of GH treatment is headaches, which can be caused by an increased pressure on the brain. If frequent headaches occur, the medication can be stopped until the headaches subside. Although rare in children, there is the potential for swelling of the extremities during the initial phases of treatment due to salt and fluid retention. Hip and knee pain can also result from a displacement of the growth plate at the femur, known as Slipped Capital Femoral Epiphyses (SCFE). While these side effects tend to be uncommon, seek medical advice to determine what symptoms you or your loved one may be susceptible to. Alternatively, growth hormone treatment can result in increased weight and bone/muscle mass, increased strength, balance/coordination, and metabolism/appetite, as well as an overall improvement in mood. 

Estrogen Replacement Therapy:

Approximately 16% girls with TS have spontaneous puberty. However, the patients who experience complete pubertal development with menarche, or adequate menstruation, only make up a small portion of that percentage, and have a mosaic karyotype, or a different grouping of cell populations in their genetics. Girls with TS most commonly experience gonadal failure, more specifically ovarian failure. On average, the transition from infancy to adolescence tends to occur around 7 to 8 years old, and menopause begins between 9 and 11 years old for these girls. Gonadotropin, the group of hormones involved in the activity of the ovaries, including estrogen, is significantly reduced in patients with TS. If you or a loved one have been recently diagnosed, estrogen replacement therapy should be an immediate consideration.

What is the Goal of Estrogen Replacement Therapy?

Due to a lack of estrogen hormone, patients with TS tend to lack certain developmental changes in secondary sex characteristics, including breast size/shape, uterine size for reproductive function, ability to reproduce, cardiovascular function, liver function, and a number of other estrogen-dependent processes. The goal is to hopefully minimize the effects of estrogen deficiency in Turner Syndrome, and normalize female growth.

How does Estrogen Replacement Therapy Work?

There are a variety of treatment options available for hormone replacement therapy. However, the ultimate goal is to mimic the normal process of puberty. The therapy process tends to start with progesterone in the early stages of menstruation, and will continue through the adjustment of estradiol levels in the blood for the remainder of the treatment. Dosages may be increased gradually as it would with spontaneous pubertal development. Estradiol is a steroid sex hormone that improves fertility and secondary sexual characteristics. It can also prevent osteoporosis, or bone deterioration. Estradiol can be administered as a gel or a patch through the skin, or it can be taken orally. However, the oral delivery causes part of the medication to metabolize into estrone sulfate, which is essentially a form of estrogen that is stored in the body rather than used actively. Although there isn’t a significant difference between transdermal and oral estradiol, recent studies indicate that the oral counterpart could have the potential to decrease antithrombin III, an enzyme that inhibits coagulation. While the research confirming these side effects is minimal, the goal of this article is to cover all information pertaining to hormone replacement therapy in TS. Without this enzyme, TS patients could be at risk for thrombosis, or a pulmonary embolism. However, these studies have only been carried out on very small control groups of post-menopausal women, and not enough evidence has been applied to adolescents to prove that this is an imminent threat is the application of oral estradiol. 

Consult your healthcare provider to find out the appropriate method of estrogen therapy for you.

How does Estrogen Replacement Therapy Correlate with Growth Hormone Treatment?

Growth hormone treatment is finished following the completion of bone growth in adolescence. At this point, the body can be prompted into beginning puberty, and estrogen therapy can be implemented. However, patients with TS can vary in their lifecycle, and it can be difficult to determine when the growth phase ends, and puberty begins. Although recent clinical guideline studies indicate that newer methods of estrogen therapy do not have an impact on the effects of growth hormone, consult your healthcare provider to find out if the growth hormone treatment provided will have the same benefit. Gonadotropin levels can also be useful for predicting future gonadal function, and the appropriate timing for hormone replacement therapy, but generally most girls with TS will begin the therapy between 11 and 14, as this is this average stage in which the menstrual cycle should start. The priority should be ensuring that the growth hormone therapy has been fully effective, I.e. she has reached her full potential prior to commencing estrogen therapy, which can then be continued until the typical age of menopause (between 45 and 55 years old). 

What Side Effects Can This Have on a Patient with TS?

Common side effects may include bloating, breast tenderness/swelling, nausea, cramps, headaches, indigestion, and vaginal bleeding, but will vary depending on the patient. While these side effects tend to only last a few weeks, they can potentially last longer, in which case an alternative method of estrogen therapy should be considered. However, the benefits of estrogen replacement therapy outweigh the consequences. Not only does estrogen replacement therapy improve physical characteristics, it can also benefit a patient with TS psychologically. It can improve both mental wellbeing, and self-esteem through the process of normalizing sexual development.

White Papers:

Studies on Turner Syndrome Patients and impacts of estrogen replacement therapy:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807900/
https://academic.oup.com/jcem/article/95/4/1487/2596297

Articles on Estrogen Therapy:

https://www.endocrineweb.com/conditions/turner-syndrome/estrogen-replacement-therapy-turner-syndrome
https://www.nhs.uk/conditions/hormone-replacement-therapy-hrt/side-effects/

Clinical Practice Guidelines Pg. 30-31, Pg. 77-84

https://vagifirm.com/uploads_cm/2015/11/women-health-menopause-4-728.jpg
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