From the Guidelines
The patient's condition suggests primary amenorrhea, and initial laboratory tests should include serum human chorionic gonadotropin (hCG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, thyroid-stimulating hormone (TSH), prolactin, and testosterone levels to determine the underlying cause. The absence of menstruation by age 13 in a girl with complete secondary sexual development (Tanner stage 5) represents primary amenorrhea, which requires evaluation to determine the underlying cause 1.
Possible Causes and Laboratory Tests
The following are possible causes and laboratory tests to consider:
- Hypothalamic dysfunction, which can be caused by stress, vigorous exercise, weight loss, and psychological disorders 1
- Outflow tract obstruction, such as imperforate hymen or transverse vaginal septum
- Ovarian insufficiency, which can be indicated by elevated FSH levels
- Anatomical abnormalities, such as Müllerian agenesis (MRKH syndrome)
- Disorders of sexual development, which may require chromosomal analysis
Initial Evaluation
Initial laboratory tests should include:
- Serum human chorionic gonadotropin (hCG) to rule out pregnancy
- Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to evaluate ovarian function
- Estradiol to assess estrogen levels
- Thyroid-stimulating hormone (TSH) to rule out thyroid disease
- Prolactin to rule out hyperprolactinemia
- Testosterone to evaluate androgen levels Additional testing may include a complete blood count, comprehensive metabolic panel, and pelvic ultrasound to evaluate the reproductive anatomy 1.
Specialist Referral
The evaluation should be conducted by a pediatric gynecologist or pediatric endocrinologist who can provide appropriate management based on the specific diagnosis. Referral to a specialist is crucial to determine the underlying cause of primary amenorrhea and to provide appropriate treatment.
From the Research
Evaluation of Amenorrhea
The patient's condition, characterized by fully developed breasts and pubic hair at 13 years old without menstruation, suggests primary amenorrhea. According to 2, primary amenorrhea is defined as the lifelong absence of menses and requires evaluation if menarche has not occurred by 15 years of age or three years post-thelarche.
Laboratory Tests
To evaluate the underlying cause of primary amenorrhea, the following laboratory tests should be ordered:
- Pregnancy test
- Serum follicle-stimulating hormone (FSH) levels
- Serum luteinizing hormone (LH) levels
- Prolactin levels
- Thyroid-stimulating hormone (TSH) levels Additional testing, such as karyotyping, serum androgen evaluation, and pelvic or brain imaging, may be individualized based on the patient's history and physical examination findings.
Hormonal Regulation
The regulation of FSH and LH is crucial in folliculogenesis and ovulation. As stated in 3, FSH concentrations rise beyond a critical 'threshold' and multiple follicles are recruited to begin pre-ovulatory development. The development-related response to LH shown by the pre-ovulatory follicle raises the possibility that exogenous LH might be used as an adjunct to therapy with exogenous FSH in clinical ovulation induction regimens.
Synergy between FSH and LH
The synergy between FSH and LH is essential for normal follicular growth and ovulation. As discussed in 4, LH plays a complementary role to FSH in regulation of the follicle, and recent studies have facilitated better understanding of the optimal dosage of LH in stimulation and its importance in advanced aged patients.
Molecular Regulation of FSH
The molecular regulation of FSH synthesis, secretion, and action is complex and involves several key players. As explained in 5, FSH is a heterodimeric glycoprotein expressed by gonadotrophs in the anterior pituitary, and its regulation involves post-transcriptional and post-translational mechanisms.
Roles of LH, FSH, and Testosterone
The roles of LH, FSH, and testosterone in spermatogenesis and folliculogenesis are crucial. As reported in 6, FSH regulates the proliferation and maturation of germ cells independently and in combination with LH, and the requirement for high intratesticular testosterone concentration in spermatogenesis remains a topic of discussion.