Turner Syndrome FoundationPrimary ovarian failure affects the vast majority of females with Turner Syndrome (TS). Estrogen plays an important role in many body functions including supporting bone health, cardiovascular protection, breast and uterus growth and development, and it influences mood and fat distribution amongst others. If estrogen replacement therapy (ERT) is not initiated and maintained during the reproductive years it can have negative impact in these areas. Hence, adequate estrogen replacement is an essential component in the care of girls and women with TS.
The optimal ERT regimen continues to be an area of study. The proper timing, form, dose and route of estrogen replacement in females with TS are all important considerations. Adolescent girls with Turner syndrome should be feminized at the normal physiologic time, preferably using transdermal estradiol which produces a more physiologic milieu in order to achieve normal levels in plasma. Learn more about hormone therapy.
The information on this page was written with contributions by Lournaris Torres-Santiago, MD and Nelly Mauras, MD of Nemours Children’s Health System, Jacksonville, FL.
Delayed Puberty Requires a Timely Intervention
The ovarian cells in females with Turner Syndrome undergo premature cell death. By 20 weeks gestation, 70% of ovarian germ cells were apoptotic in those with Turner Syndrome, compared to 3% in age-matched normal XX ovaries. The ovarian failure manifests itself as both estrogen deficiency as well as a lack of fertilizable ovum.
Girls with Turner Syndrome tend to have normal pubic and axillary hair development, as these are due to adrenal androgens, rather than ovarian estrogens. However, most girls with TS will not have full breast development nor menstrual cycles. Occasionally, there is enough residual ovarian function for breast development and/or menstrual periods. Because of the ovarian failure, natural fertilization is quite rare in women with TS.
The estrogen deficiency is treated with replacement estrogen, either as pills or estrogen patches. Studies show that estrogen patches have the advantage of not causing liver enzyme elevations and promote increased growth factor (IGF-1) levels. There are various estrogen replacement regimens that are used, but the common point among of all of them is to start with low dose estrogen, and slowly increase the dose over a couple of years. This allows for normal uterine and breast development.
Implications of a Delayed Puberty
It is psychologically beneficial for girls to experience puberty along with peer group. Girls who had not transitioned with peer group often experienced being teased and feeling left out. Shyness, social anxiety, and reduced self-esteem generally relate to the premature ovarian failure and fertility issues.
Pubertal Development
Since only a small percentage of girls will go into puberty without intervention, it is essential for the patient to discuss treatment options with their provider to coincide treatment in addition to growth hormone.
Puberty is a series of well defined stages controlled by connections between the hypothalamus, pituitary, and ovaries
• Spontaneous puberty can occur in Turner Syndrome
• More commonly, hormonal induction of puberty is required
• Treatment should be individualized for every girl
• Consideration of height and psychosocial benefits are critical in the decision-making process
• The likelihood of early ovarian failure should be discussed even with women who undergo spontaneous puberty and menarche for timely evaluation and intervention
Supportive papers:
- Pharmacokinetics and Pharmacodynamics of Oral and Transdermal 17 Estradiol in Girls with Turner Syndrome read
- Metabolic Effects of Oral Versus Transdermal17-Estradiol (E2): A Randomized Clinical Trial in Girls With Turner Syndrome read
Resources
- Puberty in Turner Syndrome, Zoltan Antal, MD, Weill Cornell Medical College Slide Presentation
- Menstruation 3 D Animation (Sherring Plough) Video
- Connecticut Children’s Medical Center Multidisciplinary Clinic for Disorders of Sexual Development (DSD) brochure
- Physician’s Referral Guide Fact Sheet
- Accordalliance.org DSD Online Resource
- DSD Resource List Fact Sheet
