Definition: Bleeding intervals longer than 35 days. Oligomenorrhea may be transient during the transition to a normal cycle. Evaluation of the physical status, sexual development, and the bleeding pattern is sufficient in this setting.

But oligomenorrhea may indicate a relevant endocrine disturbance with possible consequences for future life and health. Exploration is indicated if there are signs or symptoms of an endocrinopathy or organic manifestations. If not, a work-up should be initiated if oligomenorrhea persists for longer than 2 years.

In addition, factors such as late menarche and a prolonged interval between beginning of sexual development and menarche are indications for diagnostic evaluation.

Endocrine exploration consists of a basic hormone panel. Levels of FSH, LH, Prl, E2, T and DHEA-S are sufficient to assess the endocrine situation.

If they are all within a physiological range during development, expectant follow-up and reassurance are sufficient. Abnormal levels should be identified and their relevance assessed. Disturbances within the hypothalamus-pituitaryovarian axis as well as hyperprolactinemia and hyperandrogenemia may be detected. These abnormalities are true endocrinopathies (

table 4) and require treatment.

Hypothalamic origin: A variety of physical and psychological stresses can cause oligomenorrhea, particularly during development of the cycle. Stresses can affect the pulsatile secretion pattern of GnRH and, consequently, gonadotropin secretion. Low levels of FSH and LH and relatively low levels of estradiol are characteristic. Low body weight, eating disorders, and heavy exercise and sports are relatively common reasons.

Treatment should be initiated if oligomenorrhea persists over a prolonged period or if the long bleeding interval is disturbing. If estradiol secretion is sufficient, progestins in the second part of the cycle are an option to induce secretory conversion of the endometrium and a regular bleeding pattern. Also this prevents permanent proliferation under the influence of estradiol and thus protects against endometrial hyperplasia and carcinoma.

If estradiol secretion is low, an estrogen-progestogen combination is necessary, either as a biphasic combination of natural hormones as in early postmenopause or as a contraceptive pill. The result is a regular bleeding pattern and the correction of an estrogen deficit. Also, bone mass is preserved and osteoporosis prevented.

Pituitary origin: From a functional situation, oligomenorrhea of pituitary origin is similar to the hypothalamic form. The management is the same. Low levels of gonadotropins and estradiol are characteristic. Secondary oligomenorrhea may be a sign of an organic lesion such as a brain tumor.

The work-up should include evaluation for pituitary tumors and beginning hydrocephalus.

Hyperprolactinemic origin: Hyperprolactinemia is rare in adolescence. An elevated Prl level is diagnostic. Treatment consists of Prl inhibitors to normalize the Prl concentration and GnRH secretion and to induce a normal cycle.
Another possible reason is a cerebral tumor or pituitary adenoma.

Hyperandrogenemic origin: Hyperandrogenemia is a frequent cause of oligomenorrhea in adolescence. The increasing production of androstenedione, testosterone, dehydroepiandrosterone and DHEA-S during the development of the adrenal axis in puberty causes a transient hyperandrogenic state. Persistent hyperandrogenemia is characterized by elevated androgens; in routine assays, T and DHEA-S levels are increased. The most common form is the syndrome of polycystic ovary (PCO-S). A possible reason is late-onset AGS, which can be detected by secondary oligomenorrhea. The characteristic parameter for diagnosis is the elevated 17α-hyroxyprogesterone level.

Oligomenorrhea with PCO-S should be treated to induce regular bleeding with transformation of the endometrium to protect against hyperplasia.

The best option is a monophasic combined micropill (Ee 20 - 35μg) because the characteristic hormonal pattern is normalized by suppression of the gonadotropins and lowering of the androgens (

fig. 3). If there are symptoms of androgenization such as hirsutism, seborrhea and acne, the combination of Ee 35μg + cyproterone acetate 2mg (Diane mite) is useful because of the antiandrogenic effect of this progestin (

table 3).

Signs of androgenization can be very distressing for adolescent girls and may be an indication for the pill even if contraception is not required. Lateonset AGS is treated with corticosteroids.

Fertility later in life is reduced, particularly in patients with persistent forms of PCO-S. Weight reduction and contraceptive pill therapy may improve the prognosis for future fertility. Patients with treated AGS can become pregnant.

Ovarian origin: Oligomenorrhea caused by primary ovarian insufficiency may announce the beginning or partial damage of ovarian function. The end result may be ovarian failure with estrogen deprivation as in post-menopause and loss of fertility. Elevated levels of FSH and LH and low amounts of estradiol are characteristic. Chromosomal analysis should to be performed to exclude an abnormal karyotype. Other reasons are ovarian hypoplasia and oncologic chemotherapy with the consequence of damage of the ovarian function.

Patients with low estrogen levels are treated with an estrogen/progestogen combination in a cyclic form to induce regular bleeding and correct the estrogen deficit. Future fertility is an important aspect. Possibly ovarian function in patients at risk of ovarian failure in the future can be protected or preserved by suppressing ovarian function with an oral contraceptive or GnRH analogue.
Ovarian tissue banking may become an option in the future.