The Menstrual Cycle



Beta human chorionic gonadotropin



↓ in HPO suppression

↑ in primary ovarian insufficiency


May see >2:1 in PCOS


↓ in HPO suppression


Thyroid dysfunction


↑ in pituitary tumor


Free testosterone

↑ in PCOS

Dehydroepiandrosterone sulfate (DHEA-S)

↑ in adrenal hyperplasia/tumor


↑ in adrenal hyperplasia

aTo be drawn as an early morning sample

Primary Amenorrhea

It is important to remember that any cause of secondary amenorrhea can be a cause of primary amenorrhea (see Table 3.2). Additionally, one should focus on possible anatomic or chromosomal abnormalities as the cause of primary amenorrhea. Anatomic abnormalities can include imperforate hymen, vaginal agenesis/Mullerian agenesis, or transverse vaginal septum. While some of these findings may be visualized on an external pelvic exam, one may also need to perform a pelvic ultrasound in order to ascertain the pelvic anatomy. Pubertal timing can be key to identifying underlying chromosomal abnormalities. In normally developing adolescents, menarche follows breast development, thelarche, within 2–3 years. If breast development has not begun or if it has occurred greater than 3 years ago, one should consider an underlying chromosomal issue. Chromosomal abnormalities, indicated by an abnormal karyotype, include androgen insensitivity and Turner syndrome.

Table 3.2
Etiologies of primary and secondary amenorrhea


Immaturity of the HPO axis

Eating disorders

Exercise-induced amenorrhea/Female Athlete Triad

Medication-induced amenorrhea

Chronic illness

Stress-induced amenorrhea

Kallman syndrome





Isolated gonadotropin deficiency





Congenital adrenal hyperplasia

Cushing syndrome


Polycystic ovary syndrome

Gonadal dysgenesis (Turner Syndrome)

Primary ovarian insufficiency

Ovarian tumor

Chemotherapy, irradiation



Androgen insensitivity

Uterine adhesions (Asherman syndrome)

Mullerian agenesis

Cervical agenesis


Imperforate hymen

Transverse vaginal septum

Vaginal agenesis

Adapted from Golden NG, Carlson JL. The pathophysiology of amenorrhea in the adolescent. Ann NY Acad Sci 2008; 1135:163-178. With permission from John Wiley & Sons, Inc.

Bolded disorders indicate causes of primary amenorrhea only

Secondary Amenorrhea

In secondary amenorrhea, one is not as concerned about primary anatomic abnormalities since the outflow tract is assumed to be patent given menses have previously occurred. Rather, clinicians should focus on hormonal abnormalities that could be affecting normal menstrual function. These hormonal abnormalities are generally thought to be due to hypothalamic suppression, hyperandrogenism such as PCOS, elevated prolactin levels, or thyroid dysfunction. While several of these etiologies can be suggested by history and physical examination, laboratory evidence is usually required to make the diagnosis. Of clinical note, thyroid levels can be affected by hypothalamic suppression and may not reflect an underlying thyroid disorder. In hypothalamic suppression, one will typically see a low to normal TSH and low triiodothyronine (T3) levels [36].

Treatment of Menstrual Disorders

Treatment of the menstrual dysfunction depends on the underlying issue identified. In athletes with hypothalamic amenorrhea, restoring a normal energy balance is critical to normal hormonal resumption and, ultimately, normal bone accrual and development. As recommended in the International Olympic Committee position stand on the Female Athlete Triad, increasing dietary intake is the first step [37]. If an athlete is unwilling or unable to make appropriate dietary changes, then reducing exercise is another option. Once a more favorable energy balance is obtained, it can still take several months to a year for normal menses to resume [38]. During this time, clinicians can be monitoring serum levels of LH, FSH, and estradiol every 3 months to follow any trends. Low levels of LH, FSH, and estradiol indicate continued hypothalamic suppression. In a study of patients with eating disorders, Golden found that an estradiol level above 30 pg/mL is associated with menstrual resumption within 3–6 months in 90 % of patients [39].

Hormone Therapy in Primary Amenorrhea

In athletes with primary amenorrhea, one may consider the use of hormone replacement therapy (HRT) for the treatment of hypothalamic amenorrhea, as seen with anorexia nervosa, exercise-induced amenorrhea, and premature ovarian insufficiency [40]. The primary goals of HRT are to induce age-appropriate secondary sexual characteristics and to maximize skeletal health, although there is still limited research on the appropriate dosing for optimizing these outcomes [41]. Composed of three main phases, HRT should be individualized for each patient based on her physical and psychological needs and readiness [40]. In Phase 1, lower-dose estrogen monotherapy is used, either in a transdermal or oral preparation, to mimic the early phases of puberty in which estrogen is unopposed. During this phase, breast development and growth are stimulated. In Phase 2 of treatment, the estrogen dosages are increased, as would correspond to the hormonal shifts in a typical pubertal progression. Additionally, progestin therapy is begun to induce and maintain regular menses. Once menses have been established, Phase 3, or maintenance phase, commences in which adult serum levels of estrogen are achieved and maintained. A variety of hormonal preparations may achieve this, including combined estrogen/progesterone products in oral, transdermal, or transvaginal delivery modalities.

Hormone Therapy in Secondary Amenorrhea

The use of oral contraceptive pills to resume menses in athletes with secondary amenorrhea is often recommended by some providers, but has little evidence to support its prescription [30, 4246]. While using oral contraceptive pills may restore regular bleeding episodes, it does not restore the energy and hormonal balance that is critical for maximum bone development. Additionally, since regular periods are an important marker of a healthy weight and body, masking menstrual resumption with pill-induced menses results in a loss of an important clinical tool.


Menstrual irregularity is a common, but not a normal, finding in female athletes that encompasses a range of disorders. A thorough evaluation is warranted to investigate potential etiologies. Recent research is helping to define the underlying mechanisms of menstrual dysfunction with the leading theory being one of an insufficient energy state disrupting the HPO axis. If the Female Athlete Triad is suspected with HPO axis suppression, then restoring an appropriate energy balance is key to restoring menstrual function and maximizing health.



American Academy of Pediatrics Committee on Adolescence, American College of Obstetricians and Gynecologists Committee on Adolescent Health Care, Diaz A, Laufer MR, Breech LL. Menstruation in girls and adolescents: using the menstrual cycle as a vital sign. Pediatrics. 2006;118:2245–50.PubMedCrossRef

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Nov 2, 2016 | Posted by in SPORT MEDICINE | Comments Off on The Menstrual Cycle

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