Because the intent is to mimic normal pubertal development, therapy with low-dose estrogen alone (such as 0.025 mg per day transdermal estradiol or 0.3–0.625 mg conjugated estrogens orally each day) should be initiated.
3.
Progestins (5–10 mg medroxyprogesterone acetate or 200 mg micronized progesterone orally for 12 to 14 days every 1 to 2 months) can be added to prevent endometrial hyperplasia after the patient first experiences vaginal bleeding or after 6 to 12 months of unopposed estrogen use if the patient has not yet had any bleeding.
4.
The dose of estrogen is increased slowly over 1 to 2 years until the patient is taking about twice as much estrogen as the amount administered to postmenopausal women.
5.
Girls with gonadal dysgenesis must be monitored carefully for the development of hypertension with estrogen therapy.
6.
The patients and their parents should be counseled regarding the emotional and physical changes that will occur with therapy.
7.
It is important to educate the patient that hormone replacement therapy is usually required until the time of normal menopause to maintain feminization and prevent osteoporosis (47).
Mosaic Forms of Gonadal Dysgenesis Individuals with rare mosaic forms of gonadal dysgenesis may develop normally at puberty. The decision to initiate therapy with exogenous estrogen should be based mainly on circulating FSH levels. Levels in the normal range for the patient’s age imply the presence of functional gonads.
These individuals can become pregnant, with success rates of more than 50% using donor oocytes (48). The increased risk of sudden death during pregnancy resulting from aortic rupture should be assumed to be similar to that of other women with the Turner phenotype (40).
Pure Gonadal Dysgenesis The term pure gonadal dysgenesis refers to 46,XX or 46,XY phenotypic females who have streak gonads. This condition may occur sporadically or may be inherited as an autosomal recessive trait or as an X-linked trait in XY gonadal dysgenesis (Fig. 29.11). Affected girls typically are of average height and have none of the stigmata of Turner syndrome, but they have elevated levels of FSH because the streak gonads produce neither steroid hormones nor inhibin. When gonadal dysgenesis occurs in 46,XY individuals, it is sometimes termed Swyer syndrome. Surgical extirpation is warranted in individuals with a 46,XY karyotype to prevent development of germ cell neoplasms.
Both 46,XX and 46,XY forms of gonadal dysgenesis benefit from exogenous estrogen and are potential candidates for donor oocytes.
In early gonadal failure, the ovaries apparently develop normally but contain no oocytes by the expected age of puberty. These disorders are considered further in the discussion delineating the evaluation of amenorrhea (see Chapter 30).
Hypothalamic–pituitary disturbances are usually associated with low levels of circulating gonadotropins (with both LH and FSH levels less than or equal to 10 mIU/mL) (49). There are both sporadic and familial causes of hypogonadotropic hypogonadism, and the differential diagnosis is extensive. Mutations in several genes cause hypogonadotropic hypogonadism in humans (50). This condition can arise from abnormalities in hypothalamic GnRH secretion, impaired release of gonadotropins from the pituitary gland, or both.