Wow!! one time use of testosterone in early fetal and late fetal stages!! How do they know the boy has a micropenis before being born? Is ultrasound that accurate?
I just posted the full paper (pdf)!
The diagnosis would be made in the newborn and during the early stages, one course of testosterone would be given.
EARLY FETAL/LATE FETAL
A.
For micropenis, in neonates/children
(one course):
1. Testosterone enanthate/cypionate IM
2. Testosterone cream/gel locally
3. DHT gel locally
Figure 2. Clinical presentation of male hypogonadism according to the period of life when it is established. The testes differentiate in the first trimester of fetal life, independently of LH and FSH, the pituitary gonadotropins. Testicular hormones drive the internal and external genitalia through the male differentiation pathway. Hypogonadism established in early fetal life leads to the existence of ambiguous or female genitalia in XY newborns. In later fetal life, androgens induce testicular descent and has a trophic effect on the external genitalia. Primary and central hypogonadisms established in this period result in a male newborn with micropenis, micro-orchidism, and/or cryptorchidism. During childhood, gonadotropins and androgens are very low or undetectable; thus, hypoandrogenism is physiological. At pubertal age, the gonadal axis is reactivated, and secondary sex characteristics develop. Hypogonadism may result in absent or incomplete pubertal development, infertility, and/or sexual dysfunction. Modified, with permission, from Grinspon et al. (2019). © 2019 Elsevier Limited. This figure was created using BioRender (Home). HPG: hypothalamic-pituitary-gonadal.
In Newborns and During Infancy and Childhood.
Newborns and untreated infants and children with signs of congenital hypoandrogenism due to primary hypogonadism leading to DSD or to primary or central hypogonadism leading to micropenis and cryptorchidism in the context of male genitalia may require transient androgen therapy (Hatipoğlu & Kurtoğlu, 2013; Ladjouze & Donaldson, 2019; A. D. Rogol, 2005a,b; Wisniewski et al., 2019).
The main aims are penile enlargement and the enhancement of scrotal trophism.
The most usual practice is to give three IM doses of testosterone enanthate 25 mg every 3–4 weeks (Hatipoğlu & Kurtoğlu, 2013; Ladjouze & Donaldson, 2019; A. D. Rogol, 2005a,b; Wisniewski et al., 2019). It should be stressed that this may prove difficult, given that these oil preparations contain 200 or 250 mg in 1–2 ml. Side effects are pain and infections in the injection site, erections, and acne. These low doses of testosterone for short periods do not result in advancement of bone age or development of pubic hair.
Whether testosterone replacement should be performed during the first 6 months of life to mimic the neonatal activation of the gonadal axis is unclear; in any case, replacement would better be done with gonadotropins to promote testicular effects (Bouvattier et al., 2012; Young et al., 2019).
Percutaneous treatment has been described in infants and children with micropenis: For 30 days, 10 mg (0.2 g of 5% testosterone cream) applied daily onto the phallus at night resulted in a significant increase of approximately 9 mm in penile length without changes in bone age (Arisaka et al., 2001).
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Spreading the clinical window for diagnosing fetal-onset hypogonadism in boys
In early fetal development, the testis secretes – independent of pituitary gonadotropins – androgens and anti-Müllerian hormone (AMH) that are essential for ...
www.frontiersin.org
In early fetal development, the testis secretes – independent of pituitary gonadotropins – androgens and anti-Müllerian hormone (AMH) that are essential for male sex differentiation. In the second half of fetal life, the hypothalamic–pituitary axis gains control of testicular hormone secretion. Follicle-stimulating hormone (FSH) controls Sertoli cell proliferation, responsible for testis volume increase and AMH and inhibin B secretion, whereas luteinizing hormone (LH) regulates Leydig cell androgen and INSL3 secretion, involved in the growth and trophism of male external genitalia and in testis descent. This differential regulation of testicular function between early and late fetal periods underlies the distinct clinical presentations of fetal-onset hypogonadism in the newborn male: primary hypogonadism results in ambiguous or female genitalia when early fetal-onset, whereas it becomes clinically undistinguishable from central hypogonadism when established later in fetal life.
The assessment of the hypothalamic–pituitary–gonadal axis in male has classically relied on the measurement of gonadotropin and testosterone levels in serum. These hormone levels normally decline 3–6 months after birth, thus constraining the clinical evaluation window for diagnosing male hypogonadism. The advent of new markers of gonadal function has spread this clinical window beyond the first 6 months of life. In this review, we discuss the advantages and limitations of old and new markers used for the functional assessment of the hypothalamic–pituitary–testicular axis in boys suspected of fetal-onset hypogonadism.
The concept of male hypogonadism is usually associated with the adult patient, and rarely thought of as a condition in the prepubertal boy. Furthermore, male hypogonadism is most frequently equated to hypoandrogenism. Androgens are the dean of testicular hormones, and the normal testis produces very little or no testosterone during most of infancy and childhood. It is therefore easy to understand why the term hypogonadism is almost absent from the pediatrician’s terminology.
However, many hypogonadal states in the male bear their origin in fetal life. With the advent of direct markers of Sertoli cell function, hypogonadism can be identified in boys beyond the early post-natal critical window of pituitary–gonadal activation (1) – called “mini-puberty” by some authors – and before pubertal age. In this review, we address the diagnostic approaches of fetal-onset male hypogonadism based on the physiology and pathophysiology of the hypothalamic–pituitary–testicular axis ontogeny.
Concluding Remarks
Fetal hypogonadism of the first trimester is primary and results in dysgenetic or cell-specific forms of DSD. In the second and third trimesters, primary and central hypogonadism share signs of hypoandrogenism and defective INSL secretion – i.e., micropenis, hypoplastic scrotum and cryptorchidism – and of Sertoli cell hypoplasia – i.e., microorchidism. In prepubertal patients, classical serum markers, like gonadotropins and testosterone, are helpful essentially during the first 3–6 months of life. With the advent of AMH and inhibin B, a biochemical diagnosis can also be envisaged during the rest of childhood. Clinical findings may also help in the diagnosis beyond early infancy. Finally, the pediatrician should not expect elevated gonadotropin levels during childhood to foresee a primary hypogonadism.