A 16-old ballet dancer girl is brought to you by her mother because she is concerned of her daughter’s delayed periods. On examination, the girl has a body mass index (BMI) of 16, and breasts at Tanner II stage. No axillary or pubic hair is present. Which one of the following should come next in management?

A. Reassurance.
B. Hormonal assays.
C. Abdominal pelvic ultrasound.
D. Combined oral contraceptive pills (COCPs)
E. Referral to adolescent health centre.

Puberty in girls starts with breast development. Growth spurt then occurs and is followed by axillary and pubic hair development. Menstruation often does not take place until two years after the onset of puberty.

There are a few points in the history that can narrow down the diagnosis. Firstly, this girl has Tanner II breast at the age of 16 which shows lack of breast development as the first sign of puberty (Tanner II breasts after the age of 13 means absence of breast development).

Another point to consider is the fact that this girl has no pubic or axillary hair. This finding can be either due to arrested or delayed progression of puberty, or androgen insensitivity presented with breast development, but absence of a uterus and axillary and pubic hair. In this girl, who is a professional ballet dancer with a BMI of 16, the former is more likely.

In approaching the female patients with primary amenorrhea, the diagnostic approach depends on the presence or absence of secondary sexual characteristics. In patients with absence of such characteristics, hormonal studies including FSH, LH, TSH, prolactin is the most appropriate next step in investigations, while in the presence of such characteristics, a pelvic ultrasound for uterine or menstrual outflow abnormalities come first.

This girl has amenorrhea and absence of secondary sexual characteristics; therefore, hormonal assay is the most appropriate next step in management.

Low body weight, excessive physical exercise, and starvation are associated with hypogonadotropic hypogonadism (central hypogonadism). This is frequently observed in patients with anorexia nervosa or bulimia nervosa, but also can be seen in female athletes. Hypogonadotropic hypogonadism may result in primary or secondary amenorrhea. If it occurs during puberty, it could impede puberty from normal progression.

Although a decreased serum FSH will be the expected finding associated with the condition, with breast buds present, the most appropriate next step in management is a pelvic ultrasound. Along with physical examination, a pelvic ultrasound is always the very first initial assessment of patients with primary amenorrhea who have secondary sexual characteristics (evident by Tanner II or higher stages of breast development). Ultrasound helps to check for the presence of a uterus, mullerian agenesis, imperforated hymen, etc. as the potential causes of primary amenorrhea. Ideally, both transvaginal and transabdominal pelvic ultrasound should be performed unless virginity precludes transvaginal ultrasound.

(Option A) This girl lags behind normal puberty and cannot be reassured unless the cause is ensured to be constitutional delay of puberty.

(Option C) Pelvic ultrasound would be the correct answer if secondary sexual characteristics were present.

(Option D) Combined oral contraceptives (COCs) have no role in diagnosing or treatment of this girl.

(Option E) Referral to adolescent health center may be indicated later once other causes of primary amenorrhea other than those related to excessive exercise, weight loss, and eating disorders are excluded with high certainty. It is not appropriate at this stage when other probable causes of primary amenorrhea are not yet fully investigated.

The following are characteristic features of some important conditions associated with primary amenorrhea:

Mullerian agenesis

1-Normally developed breast (Tanner II or higher)
2-Normally developed axillary and pubic hair
3-Absent uterus

Gonadal dysgenesis (including Turner syndrome)

1-No or abnormally developed breasts 
2-Present uterus (but streak ovaries)
3-Often normally developed axillary and pubic hair
4-Increased serum FSH

Androgen insensitivity

1-Normally developed breasts (Tanner II or higher)
2-Absent uterus 
3-Absent axillary and pubic hair

Hypothalamic-pituitary failure

1-No or abnormally developed breasts (Tanner stage inconsistent with predicted age)
2-Present uterus
3-Decreased serum FSH

Mullerian dysgenesis

1-Normal breast development 
2-Normal axillary and pubic hair 
3-Normal hormonal assay (including FSH, LH, prolactin, TSH)
4-Absent uterus (and upper part of vagina)

Transverse vaginal septum/imperforated hymen

1-Normal breast development Tanner II or higher)
2-Normal axillary and pubic hair
3-Normal hormonal assay (including FHS, LH, prolactin, TSH)
4-Cyclical pelvic pain and/or suprapubic mass