Micropenis

Micropenis is usually caused by any disruption to virilization, or development of male characteristics, in infants assigned male at birth, most commonly due to low androgen levels during development. Typical male physical characteristics development occurs during weeks eight to twelve of gestation and continues after birth. Male virilization involves the integration of delicate pathways that are driven by several essential hormones. Human chorionic gonadotropin, or hCG, released from the mother’s placenta, helps stimulate testosterone production in the uterus. Testosterone is the dominant androgen involved in forming the internal male structures. Some of the circulating testosterone is converted into dihydrotestosterone (DHT), a more potent form that further stimulates the growth of male sexual characteristics, including penile growth. After birth, hormones (e.g., gonadotropin-releasing hormone [GnRH], follicle-stimulating hormone [FSH], luteinizing hormone [LH]) are released from the brain’s hypothalamus and the pituitary gland to help maintain and regulate the development of these sexual characteristics.

Micropenis is caused by virilization, a deficiency of one or more hormones. This commonly occurs during various disorders of sexual development, including Kallmann syndrome, 5 alpha-reductase deficiency, and Prader-Willi syndrome; chromosomal abnormalities, like Down syndrome and Kleinfelter syndrome; growth hormone deficiency; and other conditions, such as hypopituitarism, X-linked hypogammaglobulinemia, Carpenter syndrome, and Cornelia de Lange syndrome. 

A micropenis is diagnosed through accurate measurement of the stretched penile length, which is the distance from the pubic symphysis to the tip of the glans penis when the shaft is maximally stretched, and the foreskin retracted as much as possible. A diagnosis can be confirmed if it is less than 2.5 standard deviations from the average penile length of the same age. For example, a micropenis is defined as less than two and a half centimeters in term infants. Multiple measurements may be done to increase accuracy, using the average values for diagnosis. 

In addition, a thorough work-up needs to be conducted to understand if the micropenis is a sign of an underlying syndrome or condition, like a genetic process or a systemic hormonal abnormality. A thorough medical history of the individual and their family is essential. For instance, some medications that may have been taken during pregnancy could have had anti-androgen effects that interfered with the virilization of the fetus. A physical examination typically follows, searching for any signs that may indicate an association with a specific condition. Apart from measuring the stretched penile length, a careful evaluation of the appearance and maturation of other sexual features, such as the scrotal sac, the penile shaft, and the urethral meatus, is performed. To further investigate the underlying cause, laboratory testing of different hormone levels (e.g., testosterone, LH, FSH); radiological imaging, such as pelvic ultrasound to evaluate the gonads and internal genital structures, or brain MRI to assess the pituitary gland; as well as a karyotype to assess for numeral or structural chromosomal abnormalities may also be performed. 

Each case of micropenis is uniquely considered, but treatment typically consists of an initial hormone therapy approach chosen based on the associated syndrome. Testosterone therapy is most commonly given either intramuscularly (IM) or with a topical cream. These treatments aim to establish normal sexual and urinary function and minimize the social shame and discomfort often associated with micropenis. A surgical penile reconstruction is an additional option if medical treatment does not obtain the desired outcomes.