Why Some Teenage Girls May Never Get Their Periods

Most girls start menstruating by age 16. Primary amenorrhea refers to a female who has never had her first period by the time she is 16 years old. The term "primary" is used to distinguish this form of amenorrhea from secondary amenorrhea in which a woman has had periods but stops menstruating for one of many reasons.

Primary amenorrhea has many causes. However, the reason a teenage girl or young woman has yet to start menstruating can usually be determined with physical exam and a number of specific tests.

The investigation into primary amenorrhea begins with examination for the development of breasts and the presence of the uterus. If a young woman has begun developing breasts it suggests that she has adequate estrogen levels. The presence of the uterus suggests she had normal mullerian development as a fetus.

If breast development is present but the uterus is not:

The lack of a uterus suggests two possibilities. Two tests are required to distinguish between these two causes of primary amenorrhea, determining the karyotype (chromosome analysis) and measuring the testosterone levels.

The first possibility in a girl with breasts but without a uterus is that she is genetically female, 46XX, but had abnormal mullerian development of the reproductive organs. If this is the case, testosterone levels will be normal.

The second possibility is that she is genetically male, 46XY, but her androgen receptors are insensitive to the male hormones that would have caused her to develop male genitalia. This condition is called Complete Androgen Insensitivity Syndrome. Because she has the Y chromosome she will have high levels of testosterone when tested, she is simply insensitive to this hormone.

If breast development is lacking but the uterus is present:

A girl with no breast development and no menstruation either has abnormal ovaries that are not able to make enough estrogen despite appropriate stimulation with follicle stimulating hormone (FSH) from the hypothalamic-pituitary axis, or she has normal ovaries but does not have appropriate FSH stimulation from the brain.

These two situations are easily distinguished by testing the FSH levels. High FSH levels suggest a primary gonadal problem such as ovarian dysgenesis. This points to a problem developing as a fetus which means there is likely a chromosomal issue. Karyotyping is required.

A low FSH level, on the other hand, suggests a central cause. A hormone called Gonadotropin releasing hormone (GnRH) normally stimulates the appropriate release of FSH. Thus, low levels of GnRH can cause primary amenorrhea. Low GnRH could be due to a brain tumor, infection, or high levels of stress, intense exercise, etc.

A suspected GnRH deficiency can be confirmed by a GnRH stimulation test. If the stimulation test is positive, meaning FSH levels increase, then the cause of GnRH deficiency must be determined. An MRI of the brain is often the next step.

If breast development is present, the uterus is present, but there is no menstruation:

If a young woman seems perfectly normally for her age on physical exam, but has simply not started menstruating yet, there are a few causes to consider. The first step is to get a pregnancy test. Though uncommon, a girl can become pregnant before experiencing her first period.

Another medical condition to consider is outflow tract obstruction. She may be menstruating but the blood is unable to leave the genital tract. This may include an imperforate hymen, septae in the vagina, and other less common abnormalities. A pelvic exam and or ultrasound can evaluate these anatomic abnormalities.

Another significant cause for primary amenorrhea in an otherwise normal girl is anovulation (lack of ovulation). There are several reasons a young woman may experience anovulation including exposure to ionizing radiation, chemotherapeutic agents, and many endocrine abnormalities.

Often the first test will be prolactin levels to evaluate for a prolactinoma, the most common of pituitary adenomas. If the prolactin is high in the setting of normal thyroid stimulating hormone levels (which can cause elevated prolactin), an MRI is required. If the prolactin is normal then a progesterone challenge test may be useful to assess the girl's estrogen status. If she menstruates within 2 weeks of adminstering progesterone, she has sufficient estrogen.