medicine

1. LECTURE FIVE OVERVIEW
(Lecture 5c)
Reproductive System Development
and Disorders
© 2020. Dr. Joseph K. Choge, PhD

2. Male Reproductive System
Clinical Considerations (Continued)
Other Male RH
Anomalies:
• Klinefelter's Syndrome
• Intersexuality
(Hermaphroditism):
True I.; Male Pseudo-
(MP)
• Complete Androgen
Insensitivity Syndrome
(CAIS)
Other Male RH
Anomalies:
• Trans-Sexuality
• Trans-Genderism
=====================
Participatory Activity 5.9:
What clinically important
psychosocial issues cut across
these anomalies?

3. Male Reproductive System
Clinical Considerations – 58a
 Other Male Anomalies of the
Reproductive System
• Intersexuality
 True intersexuality
 Female pseudo-intersexuality
 Male RH Disorders:
1. Klinefelter’s syndrome*
2. Hermaphrodites* : True H.
Pseudo-H
3. Androgen Insensitivity
Syndrome (AIS)*
 Activity 5.10
1. Concerning ‘Sexual Differentiation
Defects’, what are the common
causes of male and female inter-
sexuality, respectively?
2. Describe ‘female pseudo-
hermaphrodites’; male pseudo-
hermaphrodites’; ‘True
hermaphrodites’and other related
terms.
3. Summarize about the anomalies in
male and female Reproductive
systems (comparing various
information sources and texts)
4. Enumerate male RH disorders.

4. Male Reproductive System
Clinical Considerations – 58b
B: Other Anomalies of the Reproductive System
1. Intersexuality
• c. True intersexuality:
 occurs when an individual has both ovarian and
testicular tissue (ovotestes) histologically, ambiguous
genitalia, and a 46,XX genotype.
• d. True intersexuality is a rare condition whose cause
is poorly understood.

5. Male Reproductive System
Clinical Considerations – 58c
Male RH Disorders:
1. Klinefelter’s syndrome*
2. Hermaphrodites* : True H.
Pseudo-H
3. Complete Androgen
insensitivity syndrome
(CAIS)*
Klinefelter’s syndrome.

6. Urinary System Development
Clinical Considerations – 58d
• Inter-sexuality Clinical Taster
• Read the story herein, which
depicts a typical real life
account in clinical practice*
 Activity 5.11a:
• Inter-sexuality offers a real
challenge to all stake holders .
1. List the stake holders
affected.
2. As a clinician also in the
loop, how will you deal with
the situation if a case landed
in your hands one day?
3. How is inter-sexuality
actually managed
professionally in health
sector?

7. Male Reproductive System
Clinical Considerations - 64
B: Other Anomalies of the
Reproductive System
 2. Female pseudo-
intersexuality (FP):
l. Treatment includes
immediate infusion of
intravenous saline and long-
term steroid hormone
replacement, both cortisol and
mineralocorticoids (9-
fludrocortisone).
m. The photograph in the figure
opposite shows a patient (XX
genotype) with female
pseudointersexuality
due to CYP21A2 deficiency.
Masculinization of female
external genitalia is apparent,
with fusion of the labia majora
and enlarged clitoris [(see
arrow to inset); He turned out
a boy, upon final evaluation]*

8. Male Reproductive System
Clinical Considerations - 65
 B: Other Anomalies of the
Reproductive System
 3. Male pseudo-intersexuality
(MP):
• a. MP occurs when an individual
has only testicular tissue
histologically and various stages
of stunted development of the
male external genitalia.
 These individuals have a 46,XY
genotype.
• b. MP is most often observed
clinically in association with a
condition in which the fetus
produces a lack of androgens
(and MIF).
 B: Other Anomalies of the
Reproductive System
 3. Male pseudo-intersexuality
(MP):
• c. This is caused most commonly
by mutations in genes for
androgen steroid biosynthesis
(e.g., 5-reductase 2 deficiency or
17-hydroxysteroid
dehydrogenase).
• d. Normally, 5-reductase 2
catalyzes the conversion of
testosterone (T) S
dihydrotestosterone (DHT), and
17-hydroxysteroid dehydrogenase
3 catalyzes the conversion of
androstenedione S testosterone.

9. Male Reproductive System
Clinical Considerations - 66
B: Other Anomalies of the Reproductive System
3. Male pseudo-intersexuality (MP):
• e. An increased T:DHT ratio is diagnostic (normal 5; 5-
reductase 2 deficiency 20–60).
• f. The reduced levels of androgens lead to the
feminization of a male fetus.
• g. MP produces the following clinical findings:
underdevelopment of the penis and scrotum
(microphallus, hypospadias, and bifid scrotum) and
prostate gland.
 The epididymis, ductus deferens, seminal vesicle, and
ejaculatory duct are normal.

10. Male Reproductive System
Clinical Considerations - 67
 B: Other Anomalies of the Reproductive
System
 3. Male pseudo-intersexuality (MP):
• h. These clinical findings have led to
inference that DHT is essential in the
development of the penis and scrotum
(external genitalia) and prostate gland in a
genotypic XY fetus.
 At puberty, these individuals demonstrate a
striking virilization.
• i. The photograph in the figure opposite shows a
patient (XY genotype) with male pseudo-
intersexuality.
 The stunted development of male external genitalia is
apparent.
 The stunted external genitalia fooled the parents and
physician into thinking that this XY infant was a girl.
 In fact, this child was raised as a girl (note pigtails). As
this child neared puberty, testosterone levels
increased, and clitoral enlargement ensued.
 This alarmed the parents, and the child was brought
in for clinical evaluation.

11. Male Reproductive System
Clinical Considerations - 68
 B: Other Anomalies of the
Reproductive System
 4. Complete androgen insensitivity
(CAIS; or testicular feminization
syndrome):
• a. CAIS is an X-linked recessive
genetic disorder caused by a loss-of-
function mutation in the AR gene on
chromosome Xq12, which encodes
for the androgen receptor.
 The androgen receptor is a member
of the steroid-thyroid-retinoid
superfamily of receptors.
• b. The lack of androgen receptor
function results in defective
virilization in 46,XY males despite the
presence of bilateral testes and
normal testosterone production.
 B: Other Anomalies of the
Reproductive System
 4. Complete androgen insensitivity
(CAIS; or testicular feminization
syndrome):
• c. Even though the developing male
fetus is exposed to normal levels of
androgens, the lack of androgen
receptors renders the phallus,
urogenital folds, and labioscrotal
swellings unresponsive to androgens.
• d. The testes may be found in the
abdomen, inguinal canals, or the
labia majora.
 The testes are surgically removed to
circumvent malignant tumor
formation.

12. Male Reproductive System
Clinical Considerations - 69
 B: Other Anomalies of the Reproductive System
 4. Complete androgen insensitivity (CAIS; or
testicular feminization syndrome):
• e. CAIS individuals have the following
characteristics: the presenting cause is
primary amenorrhea; there is little of no
axillary or pubic hair; there are normal-
appearing female external genitalia; the
labia and clitoris are normal or slightly
underdeveloped; the vagina is either absent
or short and blind ending; there is absence
or near absence of Müllerian structures in
the urogenital tract (i.e., uterus, uterine
tubes, cervix, superior third of the vagina);
breast development is that of a normal
female; patients are taller and heavier than
normal females; psychosocial orientation is
female; and maternal instincts are present.
• f. The photograph in the figure opposite
shows a patient (XY genotype) with CAIS.
Complete feminization of male external
genitalia is apparent.

13. Male Reproductive System
Clinical Considerations - 70
B: Other Anomalies of the Reproductive System
5. Trans-sexualism:
• This is a condition in which a person with apparently
normal bodily sexual differentiation of one gender is
convinced that he or she is actually a member of the
opposite gender.
• Although trans-sexualism has been traditionally
considered only a psychological issue, the sexual
differentiation of the brain depends on the presence or
absence of androgens, and the bed nucleus of the stria
terminalis in the brain has been implicated in sexual
differentiation of the brain.

14. Male Reproductive System
Clinical Considerations - 71
B: Other Anomalies of the Reproductive System
6. Trans-genderism:
• This is a condition in which a person decides to
have an in-between sex status.
• This type of person wants (1) to rid himself or
herself of their natal sex without seeking
reassignment to the opposite sex or (2) wants
only partial adaptation to the opposite sex.
• There may be a part-time social transition to the
opposite sex.

15. Male Reproductive System
Clinical Considerations [Summary]- 72
Summary Table of Female and Male Reproductive System Development
Adult Female Indifferent Embryo Adult Male
Ovary, ovarian follicles, rete
ovarii
Gonads Testes, seminiferous tubules,
tubuli recti, rete
testes, Leydig cells, Sertoli
cells
Uterine tubes, uterus, cervix
superior one third of vagina
Hydatid of Morgagni
Paramesonephric
duct
—
superior one third of vagina
Hydatid of Morgagni Appendix
testes
----
Appendix vesiculosa,
Gartner’s duct
Mesonephric duct Epididymis, ductus deferens,
seminal vesicle,
ejaculatory duct
Appendix vesiculosa, Gartner’s
duct Appendix epididymis

16. Male Reproductive System
Clinical Considerations [Summary]- 73
Summary Table of Female and Male Reproductive System Development
Adult Female Indifferent Embryo Adult Male
Glans clitoris, corpora
cavernosa clitoris
Phallus Glans penis, corpora cavernosa
penis, corpus
vestibular bulbs
Labia minora Urogenital folds Ventral aspect of penis
Labia majora, mons pubis Labioscrotal
swellings
Scrotum
Ovarian ligament, round
ligament of uterus
Gubernaculum Gubernaculum testes
— Processus vaginalis Tunica vaginalis
N.B: Italics indicate a vestigial structure

17. Summary
True Intersexuality:
(True Hermaphrodite)
 Possession of both ovarian
and testicular tissue
(ovotestes; histologically
evident)
 Ambiguous genitalia
 Having 46, XX genotype
Female Pseudo-Intersexuality (FP)
[Pseudo-hermaphrodite)
 An individual with only
ovarian tissue
(histologically evident)
 Masculinization of female
external genitalia
 Having 46, XX genotype
 Associated with CAH

18. Male Reproductive System
Clinical Considerations - 59
 Activity 5.13:
1. Write short notes about:
 ‘Persistent Müllerian Duct
Syndrome’ (see it’s picture
opposite).
 Hypospadias (types)
1. How do they present
clinically?
2. How are they managed
and what challenges are
anticipated during its
management?*
Persistent Müllerian Duct Syndrome
• Müllerian ducts fail to regress
• Possess both male and female sex organs

19. How to break Bad News
• Examples of 'Bad
News'
• How to break bad
news to patients*
• How to handle
reactions to the
bad news *
Activity 5.12b:
1. Give examples of areas
which consist of ‘bad
news’ to patients/clients. *
2. Outline suggested steps on
how a clinician should
handle such a situation. *

20. SUMMARY
RH Anomalies in Males & Females
Participatory Activity 5.12a:
1. Who are the Stake Holders involved?
2. What are the challenges faced by the stake
holders?
3. How are the challenges managed?
4. Counselling approaches? (Dealing with 'Bad
News')

21. How to break Bad News
Getting started:
Plan the discussion and unless really
unavoidable, don’t delegate this task;
Confirm medical facts of underlying
problem (e.g. cancer, cerebral palsy and side
effects of depo provera); Intersexuality
Create conducive environment for effective
communication;
• Ensure privacy and adequate sitting
arrangement;
• Ensure the affected person(s)/immediate
people of interest (e.g. both husband and
wife) are present for the discussion;
• Prevent interruptions during discussion
(allocate adequate and appropriate time);
Establish starting point
rapport: what the affected
person(s) (e.g. a couple)
know(s) about the underlying
problem, in order to establish
the starting point of the
discussion (e.g. intersexuality,
etc)
 Establish how much the
affected person(s) wants to
know about the problem

22. How to break Bad News
Share the information in a
sensitive but straightforward
manner;
 Do so in bits and not in a single
monologue talk, giving room for
questions and requests for
clarification from the affected
person(s) (e.g. a couple).
 Allow time for response to
feelings from the affected
person(s)
 Allow for expression of emotions (crying, anger,
sadness, love, anxiety, guilt, e.t.c);
Plan for way forward:
E.g:
•Inter-sexuality: Visit specialist for scheduling
surgical operations; appropriate medications
•Cerebral palsy will require occupational therapy,
frequent treatment of recurrent infections, special
schools attention, acceptance of reality by whole
family and friends;
•Secondary Infertility: will require further tests to
confirm irreversibility of fertility or specialized
treatment of the same; Child adoption may be
discussed as an option for the couple if they so wish.
•Cancer diagnosis: Radiotherapy; Chemotherapy;
Combined Chemotherapy and Radiotherapy; Hospice
personnel and counselors involvement in the
management of the patient and the affected family.