Phallic Development Research Articles

Disorders of Sex Development.

Disorders of Sex Development.

Commentary on Federica Melandri’s “Milk and Tears”

ABSTRACTDr. Melandri’s use of the 2001 Revised Diagnostic Profile to assess 5-year-old Leo brought forth different emphases than Anna Freud’s original Diagnostic Profile (1965). Dr. Melandri’s explicit sharing of how she reacted to and felt in Leo’s presence is far more explicit. Another difference is how fluently Dr. Melandri integrates metapsychology with diverse clinical theories to describe Leo’s development. Had the original Diagnostic Profile been used, there would have been greater emphasis on libidinal phase development, such as orality, anality, phallic, and oedipal development, not to mention dynamic and structural achievements. This essay asks: “what’s at stake?” regarding these different emphases. The author concludes with a few remarks in general about the 2001 Revised Profile, including comments about the fate of Freud’s and Anna Freud’s radical vision.

Aphallia in an adult

Aphallia or penile agenesis is complete absence of the penis due to complete or partial failure in the phallic development of the genital tubercle. It is a rare form of genital ambiguity with an estimated incidence of 1 in 10-30 million births and <100 cases reported till date. Very few cases have survived to adulthood. We report a case of aphallia, who presented to us at the age of 45. Clinical presentation in an adult is the absence of the penis with a normal scrotum, normally descended testis and well developed secondary sexual characters. This is best evaluated by magnetic resonance imaging while treatment options vary from gender reassignment during infancy to phalloplasty and urethral transposition in adulthood. Preservation of urinary continence and maintenance of urinary outlet should be the primary aim of treatment of aphallia in an adult.

Virilization in two pre-pubertal children exposed to topical androgen

Androgen replacement therapy for male hypogonadism may be prescribed utilizing intramuscular, oral or more recently, topical formulations. With topical formulations, there is a risk of person-to-person transmission if appropriate precautions are not taken. We describe two cases of virilization in pre-pubertal children following passive transfer of paternal topical testosterone. A 21 month old male was referred with a 6 week history of pubic hair, phallic growth, and linear growth spurt. Genital examination revealed Tanner stage 2 pubic hair and Tanner stage 3 phallic development, which was discordant with the pre-pubertal testicular size (2 mL bilaterally). A 3 year 8 month old girl was referred for a 2 month history of increasing pubic hair development. Examination revealed Tanner stage 2 pubic hair and Tanner stage 1 breast development. Both of these patients had fathers who had been diagnosed with hypogonadism and were being treated with topical androgen gel therapy, which they applied to their arms and chest before bed. In addition, both patients often slept with their parents resulting in skin-to-skin contact. Investigations were consistent with gonadotropin independent virilization with both patients demonstrating elevated testosterone levels. Testosterone levels returned to normal pre-pubertal levels with no further development of secondary sexual characteristics following discontinuation of exposure to topical testosterone. Precautions must be taken to prevent person-to-person transfer of topical steroids. With the increasing popularity of topical steroids for the treatment of low testosterone, it is imperative that these therapies be prescribed and utilized judiciously to prevent harm, specifically gonadotropin-independent virilization.

Congenital Aphalia associated with Thoracic Hemivertebrae -A Case Report

While one in 1000 to 2000 neonates are born with anatomically ambiguous genitalia, penile agenesis or aphallia, is an extremely rare phenomenon for there are approximately only 60 reported cases as of 1989, and 75 cases as of 2005.1 It usually coexists with other anomalies which may be compatible or incompatible with normal life. Aphallia or absence of phallus ((penis or clitoris) is a very rare congenital anomaly that can occur in both males and females. A two month year old baby, born out of an uncomplicated pregnancy and with no family history of any other congenital anomalies or consanguinity was brought to our hospital, with complaints of absence of penis by the mother. Examination revealed a healthy child, with normal scrotum, bilaterally descended testis, with an anteriorly placed ectopic anus but with an absent penis. There was absence of a urethral meatus in the perineum, the urethra was later diagnosed as opening to the anterior part of the rectum. Ultrasonography revealed bilaterally normal kidneys. Radiological examinations revealed associated multiple thoracic hemivertebrae. Agenesis of the penis is a result of complete or partial failure in phallic development of the genital tubercle and failure in caudal migration of the urogenital sinus during the embryonic development. Infants with aphallia are usually raised as female so the aim of treatment in such cases is an early female gender assignment and feminizing reconstruction of the perineum, followed by oestrogen therapy to promote secondary sexual characters. The occurrence of hemivertebrae in cases of aphalia is very uncommon and not yet reported so far. So careful neonatal radiologic evaluation is essential to detect the association of such extremely rare skeletal anomalies which if not treated promptly may manifest in severe deformities in later life.

Endocrine differentiation of fetal ovaries and testes of the spotted hyena (Crocuta crocuta): timing of androgen-independent versus androgen-driven genital development

Female spotted hyenas (Crocuta crocuta) have an erectile peniform clitoris and a pseudoscrotum but no external vagina, all established by day 35 of a 110-day gestation. Recent studies indicate that these events are androgen-independent, although androgen secretion by fetal ovaries and testis was hypothesized previously to induce phallic development in both sexes. We present the first data relating to the capacity of the ovaries and testes of the spotted hyena to synthesize androgens at different stages of fetal life. Specifically, spotted hyena fetal gonads were examined by immunohistochemistry at GD 30, 45, 48, 65, and 95 for androgen-synthesizing enzymes, as related to the morphological development. Enzymes included 17alpha-hydroxylase/17,20-lyase cytochrome P450 (P450c17), cytochrome b5, 3beta-hydroxysteroid dehydrogenase (3betaHSD), and cholesterol side-chain cleavage cytochrome P450 (P450scc). Anti-Müllerian-hormone (AMH) expression was also examined. AMH was strongly expressed in fetal Sertoli cells from GD 30 and after. P450c17 expression was detected in Leydig cells of developing testes and surprisingly in Müllerian duct epithelium. Fetal ovaries began to organize and differentiate by GD 45, and medullary cells expressed P450c17, cytochrome b5, 3betaHSD, and P450scc. The findings support the hypothesis that external genital morphology is probably androgen-independent initially, but that fetal testicular androgens modify the secondary, male-specific phallic form and accessory organs. Fetal ovaries appear to develop substantial androgen-synthesizing capacity but not until phallic differentiation is complete, i.e. after GD 45 based on circulating androstenedione concentrations. During late gestation, fetal ovaries and testes synthesize androgens, possibly organizing the neural substrates of aggressive behaviors observed at birth in spotted hyenas. These data provide an endocrine rationale for sexual dimorphisms in phallic structure and reveal a potential source of androgenic support for neonatal aggression in female and male C. crocuta.

Consultation with the specialist: hypospadias.

1. Warren T. Snodgrass, MD* 1. *Department of Urology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX After completing this article, readers should be able to: 1. Describe the incidence and cause of hypospadias. 2. Determine when evaluation for intersexuality should be considered in a child who has hypospadias. 3. Delineate when boys who have hypospadias should undergo surgical correction. A term baby is found on initial newborn examination to have penoscrotal hypospadias. The family is distressed and asks several questions: 1. Does he have any other problems, and is this an intersex condition? 2. Does he need other tests? 3. Can he urinate the way he is? 4. Why did this happen, and since we never heard of it before, how common is it? 5. Can it be fixed, and if so, when? Who should do the surgery? 6. We planned to have you circumcise him; can you still do that? Hypospadias refers to incomplete urethral development that results in a meatus located anywhere from the proximal glans to the perineum. The condition occurs in approximately 1 in 150 to 1 in 300 males, making hypospadias the second most common birth defect in boys after cryptorchidism. Recent surveys suggest that the incidence of hypospadias is increasing in industrialized countries, possibly due to environmental estrogens or antiandrogens. The external genitalia are initially indifferent and, in the absence of androgen, inherently develop the female phenotype. The critical timeframe for phallic development is from 8 to 12 weeks’ gestation, when the genital tubercle elongates and the urethral plate on its ventral surface tubularizes from proximally to the tip of the glans. During this phase, the penis is curved ventrally because the corpora cavernosa, as well as shaft skin and prepuce, develop faster on the dorsal than the ventral aspect. After 12 weeks’ gestation, androgen stimulation increases the size of the phallus. Hypospadias results from an arrest in these normal processes. The incompletely tubularized urethra opens on the undersurface, …

Unsolved problems in male physiology: studies in a marsupial

Testicular androgens induce formation of the male urogenital tract in all mammals. In marsupials male development occurs after birth and over a prolonged period. For example, in the tammar wallaby virilization of the Wolffian ducts begins by day 20, prostate formation begins about day 25, and phallic development starts after day 80 of pouch life. Between days 20 and 40 5α-androstane-3α,17β-diol (5α-adiol) is formed in tammar testes and secreted into plasma. Administration of 5α-adiol to pouch young females induces urogenital sinus virilization by day 40 and formation of a mature male prostate and phallus by day 150. 5α-Adiol is synthesized in pouch young testes by two pathways, one involving testosterone and dihydrotestosterone and the other 5α-pregnane-3α,17α-diol-20-one and androsterone as intermediates, both utilizing steroid 5α-reductase. In target tissues 5α-adiol acts via the androgen receptor after conversion to dihydrotestosterone but may have other actions as well. Whether 5α-adiol plays a role in male development in placental mammals is uncertain.

URETHRAL DEVELOPMENT IN THE FETAL RABBIT AND INDUCTION OF HYPOSPADIAS: A MODEL FOR HUMAN DEVELOPMENT

To determine whether the development of the rabbit phallus would be an appropriate model of human phallic development, we evaluated the formation of the fetal rabbit phallus and attempted to induce hypospadias pharmacologically. New Zealand rabbit fetuses were obtained on gestational days 20 to 24, 26, 28 and 31. Sex was determined by gonadal morphology, and 6 fetuses were obtained at each age. The perineum was dissected, fixed, sectioned and stained with hematoxylin and eosin, and monoclonal antibodies against neuronal specific enolase. Two pregnant rabbits were treated with 10 mg./kg. finasteride orally daily between gestational days 19 and 28. The development of the external genitalia was compared in treated and untreated control rabbits. The rabbit phallus contains 2 corpora cavernosa and dorsolateral nerves similar to the human. In male and female fetuses fusion of the urethral folds progressed in a proximal to distal sequence forming a seam at the point of ventromedial fusion. In male fetuses urethral fold and ventral preputial fusion continued more distally toward the glans compared to females. Thus, in mature males the urethral meatus and ventral prepuce extended to the tip of the phallus, whereas in females the urethral meatus opened on the proximal phallus and the prepuce was deficient ventrally forming a dorsal hood. Male offspring had a significantly larger anogenital distance postnatally than female offspring. In male fetuses exposed to finasteride urethral fusion did not extend distally and the prepuce was deficient ventrally. Also, male offspring exposed to finasteride in utero had a significantly shorter anogenital distance than females and untreated control males at all ages (p <0.05). Fetal development of the rabbit phallus and urethra is homologous to the human. Although the gestational period is significantly shorter, the temporospatial pattern of external genitalia development is analogous in these species. Feminization of the rabbit urethra, hypospadias, can be induced by inhibiting 5alpha-reductase. Use of this animal model will allow further study of molecular mechanisms involved in urethral fusion and the evaluation of the pathophysiological processes of hypospadias.

Prenatal Diagnosis of Cloacal Dysgenesis Sequence: Differential Diagnosis from Other Forms of Fetal Obstructive Uropathy

Cloacal dysgenesis sequence (CDS) is a rare cause of fetal obstructive uropathy (FOU). The prenatal differentiation of CDS from other FOU is important because CDS is not amenable to in utero surgical intervention in the form of vesicoamniotic shunts. We evaluated the prenatal characteristics of 8 fetuses with CDS, including a pair of monozygotic twins concordant for CDS, in order to identify features that would enable differentiation from other forms of FOU. Pathologic examination in each of the 8 fetuses confirmed characteristic features of absent anal, genital, and urinary orifices associated with a smooth perineum and abnormal phallic development. Associated abnormalities included dysplastic kidneys in 6, hydroureters in 5, intraluminal colonic calcifications in 2, and hypoplastic lungs in 5. Five of these fetuses initially presented as posterior urethral valve syndrome. Six fetuses had megacystis, and 4 underwent vesicocenteses to evaluate urinary electrolytes, all of which were in the ‘poor-risk’ category. Six fetuses were male and 2 female, contradicting earlier claims that CDS occurs only in females. Evaluation of candidates for in utero surgical intervention should include fetal karyotype, and CDS should be suspected in cases of FOU in whom the karyotype reveals a male fetus and sonographic evaluation demonstrates colonic calcifications or abnormal phallic development. Diagnostic microendoscopy may be of benefit in such cases.

Congenital Adrenal Hyperplasia: Is there an Effect on Penile Growth?

Purpose Experimental evidence in rodents suggests that prepubertal exposure to excess androgens may prematurely down regulate the penile androgen receptor and cause micropenis in adulthood. To evaluate the effect of prepubertal androgens on human penile growth we reviewed phallic development in male patients with congenital adrenal hyperplasia. Materials and Methods We retrospectively reviewed the records of 12 patients with hydroxylase deficiency. Stretched penile length was recorded at diagnosis and at last followup. Bone age, height and weight were recorded at each visit. Results At diagnosis mean z-score for stretched penile length (z-score equals the number of standard deviations above or below the mean, that is z-score for micropenis equals -2.5) was 2.95 (1.23 to 4.88). Final mean z-score for stretched penile length in adulthood was -1.70 (-2.96 to 1.87). Mean decrease in z-score from diagnosis until the last followup was -4.68 (-1.08 to -6.82). Only 2 of the 12 patients (17 percent) had micropenis in adulthood. Notably excessive adrenal androgen production resulted in diminutive stature with median height in adulthood in the 10th percentile. Conclusions These findings suggest that excessive prepubertal androgen exposure due to congenital adrenal hyperplasia is associated with a reduction in adult somatic height but it does not routinely result in micropenis.

Pathogenesis of hypospadias—More questions than answers

Most researchers believe that hypospadias arises from malformation of the penile urethra. However, this concept has been recently rejected, and it has been suggested that the opening of the urethra is "pushed forward" by growth of the perineum. In order to obtain more information on the development of the urethra, late stages of phallic development were studied in 220 rat embryos with scanning electron microscopy (SEM). In our study, signs of rupture of the urogenital membrane or fusion of the urethral folds could not be found. Therefore, we could not confirm the traditional concept for the development of the phallic urethra. A new concept of urethral development is suggested and the pathogenesis of hypospadias is discussed.

Diagnosis of the Partial Androgen Insensitivity Syndrome During Infancy

WHEN a child is born with ambiguous genitalia, the sex of rearing becomes of preeminent importance. Androgen insensitivity must be recognized in those genetic males with borderline phallic development if appropriate assignment as females is to be made. The androgen insensitivity syndrome (AIS) may occur in the complete form (CAIS), in which no masculinization of the external genitalia occurs during fetal development and rearing clearly should be female, and the partial form (PAIS), in which varying degrees of virilization of the external genitalia occur. The latterform presents at birth with ambiguous genitalia and must be differentiated from other forms of male pseudohermaphroditism. If CAIS is diagnosed during infancy, the clinical presentation may include the presence of palpable inguinal gonads, inguinal herniae, or both.¹Partial androgen insensitivity syndrome may be diagnosed in infants with ambiguous genitalia and a 46,XY genotype. The defect in CAIS may be caused by absent

Partial impulse erogeneity as a function of fixation and object relations

The psychoanalytic theory of adult erogeneity is analyzed with respect to differential sexual and foreplay activities. Psychosexual fixation within any of the basic stages of oral, anal, or phallic development was hypothesized to correlate negatively with adult erogeneity in that respective area. The overall investment in sexuality across the erogenous areas was expected to be a function of the general level of development within the object relations domain, so that the less narcissistic and more other‐oriented a person is, the more investment is to be expected in interpersonal sexuality. Utilizing recently developed psychometric instruments measuring these analytic constructs, self‐report erogeneity data from 56 women were analyzed and compared with fixation and object relations variables. Results confirmed the object relations hypothesis. A comparison of the intercorrelations of the erogeneity and fixation variables showed that although the pattern is in line with the hypothesis, statistical significanc...

Phallic Integration and Male Identity Development

Phallic Integration and Male Identity Development

Supportive testosterone treatment in surgical repair of hypospadias

Hypoplastic development of the phallus renders repair of hypospadias more difficult and very often limits functional and cosmetic results. We therefore tried to simplify surgery and to improve results by perioperative low-dose intramuscular testosterone treatment. 9 children with hypospadias of varying degree were treated with testosterone enantate 25-250 mg x 3 (2 injections at 3 weeks intervals preop. and 1 injection postop). Bone age, growth and phallic development were followed up to 2 years. While there was a reliable degree of phallic growth in most of the boys, in only 3 of the children we observed a slight transitory acceleration of skeletal development, in 7 a transitory increase of growth rate. No signs of virilisation were noted. We believe that in selected cases of hypospadias a short-term low-dose testosterone treatment may be an acceptable means to simplify and improve repair.

Effects of testosterone propionate administered perinatally on sexual behavior of female ferrets.

Female ferrets that received injections of testosterone propionate (TP) early in postnatal life displayed significantly more masculine behavior than did control females when gonadectomized and administered either TP or estradiol benzoate in adulthood. This increased masculine response potential was not correlated with the effects of early TP treatment on phallic development. In contrast to results obtained in most other species, perinatal administration of TP to female ferrets failed to disrupt their ability to display the behavior that is characteristic of the sexually receptive animal in estrus. When estrogenic stimulation was provided in adulthood, the receptive behavior of three groups of perinatally androgenized females was indistinguishable from that of both male and female controls. However, after gonadectomy and administration of TP, control males and females that had received TP prenatally plus on Day 3 were significantly more receptive than were control females. The induction of receptivity by TP was significantly inhibited by simultaneous administration of the antiestrogen MER-25.

Inhibition of lordosis in female rats by subcutaneous implants of testosterone, androstenedione or dihydrotestosterone in infancy

Female rats were implanted on the day of birth with Silastic capsules containing nonesterified testosterone, androstenedione, or dihydrotestosterone. The date of vaginal opening was assessed until sacrifice. The animals were ovariectomized, treated with estradiol benzoate and progesterone, and tested for the display of lordosis. The animals were then administered testosterone propionate and the size of the phallus was taken. Testosterone and dihydrotestosterone completely inhibited vaginal opening; androstenedione was partially effective. Testosterone almost completely inhibited lordosis behavior; androstenedione was partially effective and dihydrotestosterone was ineffective. All three androgens facilitated phallic development.

The effects of castration at different intervals after birth on the copulatory behavior of male hamsters ( Mesocricetus auratus)

The copulatory behavior of 24 male hamsters castrated either 1, 5, or 10 days postpartum was investigated. As adults, the males were given four tests for female behavior after injections of estrogen and progesterone. One month after the last test for female behavior, males were injected with 200 μg testosterone propionate per day for 28 days and tested for male behavior on Days 7, 14, 21, and 28 of treatment. The hormone dose was then increased to 400 μg testosterone propionate per day for 7 days followed by testing for male behavior. Female copulatory behavior (lordosis duration) and several components of the male copulatory pattern were significantly but differentially affected by the timing of postnatal castration. Only the frequency of intromission and ejaculation covaried with the amount of phallic development.

Manipulation of neonatal androgen: Effects on sexual responses and penile development in male rats

Male rats castrated at four days of age were given fluoxymesterone (FM) or testosterone (TP) for the next seven days. As adults they were given exogenous testosterone and tested for mating behavior. Most FM animals intromitted frequently but were incapable of ejaculation, whereas all TP animals showed the complete mating sequence. Since phallic development in FM animals was equal to that of TP animals, this behavioral difference was attributed to some difference in development in the central nervous system. After a spinal transection was performed on the same animals, tests for penile reflexes revealed no differences between FM and TP animals, indicating that this differential development was in the brain. In another experiment male rats were castrated at 7 days of age, given exogenous testosterone in adulthood, and tested for mating behavior; about half of these animals were capable of ejaculation. There did not seem to be sufficient differences in phallic development between the ejaculators and nonejaculators to account for the ability or inability to ejaculate. These results and other observations from the two experiments are consistent with the concept that although the neural basis for mounting and intromission behavior in rats may be organized independently of neonatal androgen, the neural substrate controlling ejaculation behavior does require the influence of neonatal gonadal androgen for complete development.