Androgens are steroid hormones produced in adult female ovaries and male testis and in adrenal gland. It is essential for sexual development and reproduction.

1. University of Chakwal, Pakistan

2. Topic: Androgenic Hormones Disturbances
Department of Zoology
Presented by: Hifza Arif
Reg. No.# UOC-BSZOL-F2020/022
Session: 2020-2024
Course Title: Endocrinology
Instructor Name: Dr. Syeda Nadia Ahmad

3. Contents:
❖Introduction
❖Discovery
❖Types
❖Concentration in body
❖Importance
❖Production
❖Role
❖Genetic Disturbances
❖Excess/Deficiency
❖Recent Approaches
❖Future Direction

4. ❖ Introduction
Androgens are steroid hormones.
Produced in the adult female ovaries and male testes, and in
adrenal glands.
Essential for sexual development and reproduction.
Also modulate other organs including bone, muscle, adipose
tissue, skin, hair , the brain, and the cardiovascular system,
thereby effecting growth, body shape and human behavior
(Elzenaty, 2022).

5. ❖ Discovery
 Term “androgen” is derived from the Greek words “andros”
(meaning, man) and “gen” (meaning, to generate).
 Concept of androgens, male sex hormones, dates back to the 18th
century when scientists began to understand their role in male
sexual development.
 Androgens were first discovered in 1936.
 Later, it is explained, they are also the original anabolic steroids
and the precursor of all estrogens, the female sex hormones.

6. ❖ Types of Androgens
Testosterone: the predominant androgen in all genders
Dihydrotestosterone (DHT)
Dehydroepiandrosterone (DHEA)
Dehydroepiandrosterone-sulfate (DHEA-S)
Androstenedione

7. ❖ Concentration of Androgens in Males and
Females
Conc. in Males:
 In male adults, testosterone is the most abundant androgen produced in testes
that is present in circulation.
 Total testosterone concentrations are about 10-30 nmol/L at age 30 years in
men and decline at an average rate of 1-2% per year with aging.
 Testosterone can be converted to the most potent endogenous androgen,
dihydrotestosterone (DHT).
 DHT has about 5-10-fold greater affinity for androgen receptor compared to
testosterone (Elzenaty, 2022).

8. Conc. in Females:
 In a 30 year old woman, the most abundant androgens in circulation are
dehydroepiandrosterone-sulfate (DHES-S; 1.2-10 nmol/L),
dehydroepiandrosterone (DHEA; 0.1-23 nmol/L) and androstenedione
(0.5-7.9 nmol/L).
 These all are considered weak androgens according to their low affinity
towards the androgen receptor.
 However, these weak androgens can be metabolised to more potent
androgens (such as testosterone or dihydrotestosterone) in peripheral
tissue through multiple pathways (Elzenaty, 2022).

9. Conc. in Menstruating Females:
 In menstruating women, circulating androgens originate in part from
the adrenal cortex ( mainly DHEA and DHEA-S) and more so from the
ovaries (androstenedione).
 Total plasma testosterone levels of a 30 year old woman are about 10 to
15 fold lower than in a same –aged male (0.4-2.1 nmol/L).
 After menopause, when ovarian steroidogenesis has ceased, circulating
androstenedione levels are cut in half and total testosterone levels
decrease by about 25% (Elzenaty, 2022).

10. ❖ Importance of Androgens in both Males and Females
 Testosterone is the primary male sex hormone which is responsible for the development of
male reproductive organs and secondary sexual characteristics such as facial and body hair,
deepening of the voice, and increased muscle mass. It is also crucial for maintaining bone
density and muscle mass in both males and females.
 Dihydrotestosterone (DHT) is derived from testosterone and is vital for the development
of male external genitalia. In females, it is involved in maintaining the health of hair
follicles and sebaceous glands.
 Dehydroepiandrosterone (DHEA) is produced in larger quantities in females and serves
as a precursor to both testosterone and estrogen. It helps in maintaining hormonal balance in
both males and females.
 Dehydroepiandrosterone-sulfate (DHEA-S) acts as a reservoir for DHEA and plays a
crucial role in various bodily functions, including immune response, in both males and
females. It is also essential for normal ovulation and plays a crucial role in initiating and
regulating puberty in females.
 Androstenedione, a precursor to both testosterone and estrogen, has implications for
reproductive and bone health, and also helps in maintaining hormonal balance in the body,
in both males and females.

11. ❖ Production of Androgens
 Production of androgens in adult gonads is controlled by the hypothalamus
pituitary gonadal (HPG) axis, which involves the gonadotropin releasing
hormone (GnRH), luteinizing hormone (LH) and follicular stimulating
hormone (FSH), and comprises of balanced feed-forward and feed-back loops.
This system is sex specific and characterized by the testis or ovary as target
organs.
 Within the testis, leydig cells produce and secrete testosterone abundantly. By
contrast n the ovary, theca cells produce androstenedione, that is mostly
transferred to granulosa cells as precursor for the production of estrogens,
while only small amounts are secreted into circulation (Elzenaty, 2022).

12. Fig. 1: Androgen Biosynthesis
https://images.app.goo.gl/vyJtrcRfuAMx5pcT8

13. Fig. 2: Androgen Secreting and Expressing Tissues
https://images.app.goo.gl/v7f5417eJnK9cvfr5

14. ❖ Role of Androgens
All Genders Males Females
Other body chemicals convert
androgen into estradiol, a
form of “estrogen”. This
hormone:
▪Bone density ▪Deep voice (vocal cord
lengthening)
▪Regulates mensturation
▪Muscle development ▪Hair growth on face, scalp,
chest, underarms, and genitals
▪Aids conception and
pregnancy
▪puberty ▪Sperm development ▪Minimizes bone loss
(osteoporosis)
▪Red blood cells production ▪Stimulates pubic and
underarms hair growth
▪Sexual desire and function

15. ❖ Androgenic Hormones Disturbances
 Males and females need androgens and its action to develop normally and
stay healthy, but the dosage of androgens is highly sex specific.
 Both androgen deficiency and excess may lead to endocrine disorders that
may manifest with a phenotype of disorders of sex development at birth,
disturb pubertal development, and sexual functioning and fertility.
 Both lack and excess of androgen action may also manifest at any time of
life with adverse effects on other organ systems including overall
metabolism, the cardiovascular system, muscles, bones, brain and
psychological system (Elzenaty, 2022).

16. ➢ Manifestations of genetic disorders of gonadal and
adrenal steroidogenesis:
 During fetal development, the liver and the placenta play major roles in this
network.
 The fetal liver, functions to metabolise and inactivate androgens, and while the
placenta is not considered an androgen producing organ, it does express all the
necessary steroidogenic enzymes to convert maternal progesterone to androgens,
including those that can biosynthesise testosterone.
 Notably, placental aromatase would convert androstenedione and testosterone to
estrogens, while other androgens might not be biotransformed to estrogen
derivatives in vivo (Elzenaty, 2022).

17.  As the development of the typical female and male external genitalia relies largely
on the absence or presence of testosterone and dihydrotestosterone, any disturbance
in androgen production may result in apparent virilization of a female fetus or
under-masculinization of a male fetus.
 After birth and minipuberty, gonadal steroidogenesis is quiescent until puberty,
when activation of the hypothalamus pituitary gonadal axis commands to resume
sex steroid production for normal sexual maturation, fertility and reproduction.
 Also, in postnatal/adult life, steroids secreted by the adrenals and gonads are
converted to active and inactive metabolites by peripheral organs, and this complex
peripheral steroid metabolism may then be responsible for the formation of unusual
steroids through alternate pathways in genetic disorders of steroidogenesis
(Elzenaty, 2022).

18. ➢ Specific Monogenetic Defects of Androgen Biosynthesis:
 Pathogenic variants in all genes involved in human androgen biosynthesis and
metabolism may cause androgen deficiency or excess.
 Genetic defects affecting early steps of steroid biosynthesis and cortisol
production in particular are known as congenital adrenal hyperplasia (CAH).
 According to the current disorders of sex development classification, these
disorders may be grouped in defects causing;
1. Male disorders of sex development CAH
2. Female disorders of sex development CAH
3. Disorders of sex development CAH in both chromosomal sexes (Elzenaty, 2022).

19. First group Second Group Third Group
Male disorders of sex development CAH Female disorders of sex development CAH Disorders of sex development CAH in both
chromosomalsexes
Mutations in the genes i.e. StAR,
CYP11A1, CYP17A1
Mutations in the genes i.e. CYP21A2 and
CYP11B1,
These genes are necessary for
glucocorticoids and mineralocorticoid
synthesis, in adrenal cortex.
Genetic mutations in 3b-hydroxysteroid
dehydrogenase type II (HSD3B2) and
cytochrome P450 oxidoreductase (POR)
Lack of androgens Excess of androgen
Individuals are not able to synthesize
cortisol and androgens.
It causes the lack of cortisol, that elevates
adrenocorticotropic hormone (ACTH) and
thus increased adrenal androgen
production.
Manifest with cortisol deficiency
Affected chromosomalmale fetuses are
born with typical female external genitalia
and raised
Affected girls show variable degrees of
external genital virilization at birth
Variable severity of disorders of sex
development at birth in both chromosomal
sexes depending on the specific variants
Affected boys have no disorders of sex
development phenotype but still suffer from
neonatal onset adrenal insufficiency with
severe variants.

20. ➢ Genetic Defects of Androgen Action- Androgen
Insensitivity Syndromes
 Androgen insensitivity syndrome (AIS) is a rare, inherited, sexual
development disorder. People with AIS are genetically male, but don’t
develop male external genitals because their bodies can’t respond to male
sex hormones. AIS can cause problems during puberty, as well as infertility.
 Complete or partial androgen insensitivity syndromes (CAIS/PAIS) are
caused by genetic mutations affecting androgen receptors function. In these
syndromes of male phenotypic under-masculinization, androgen
concentrations are typically elevated (Elzenaty, 2022).

21. AIS Type I
 AIS incidence is reported internationally in 1 in
20,400 live born male infants, with CAIS
occurring at a higher rate than PAIS.
 AR mutations have been described in individuals
with AIS, classified as AIS type I.
 In CAIS, severe hemizygous androgen receptor
mutations cause the loss of androgen receptor
signaling
▪ Affected male individuals show male typical inner
genital organs and undescended gonads with the
prostate, vas deferens and seminal vesicles missing.
External genitalia are typical female with a vaginal
pouch.
▪ Female carriers are phenotypically normal.
 In male PAIS, the phenotypic variability in under-
masculinization is large and depends on the
residual activity of the androgen receptor.
▪ In the mildest form of PAIS, gynecomastia and
male infertility may be the only clinical signs.
AIS Type II
 By contrast, individuals with AIS without
AR mutations are classified as AIS type II.
 In these individuals largely unidentified
regulators or cofactors of the androgen
receptor (AR) are responsible for the
impaired AR signaling as revealed by an
AR-dependent bioassay using genital skin
fibroblasts and the targeted APOD as a
biomarker.
 As AR activity can be regulated at various
levels, the possible mechanisms of AIS
type II are manifold. Thus far, altered DNA
methylation of the AR promoter has been
found in some individuals with PAIS.

22. ❖ Acquired Disorders of Androgen Excess
and Deficiency
Hyperandrogenism
 It is a condition in which the
body produces too much
androgen. It is most common
in women of reproductive age,
but it can also occur in men
and children.
Hypoandrogenism
 It is a condition in which the
body produces too little
androgen. It is most common
in men, but it can also occur in
women and children.

23. ➢ Androgen Excess in Males:
Symptoms Effects Treatment Common Disorder
▪ Increased Body
Hair
▪ Acne
▪ Muscle Mass
▪ Baldness
▪ Reduced
Testicular Size
▪An altered physical
appearance.
▪Potential
psychological effects.
▪LifestyleChanges:
managing weight,
improving diet, and
exercising can help.
▪Surgery: In cases of
tumors, surgical
removal may be
necessary.
▪ProstateCancer:
Prostate cancer
growth and
development critically
dependent on
androgens and
androgen receptor
signaling.

24. ➢ Androgen Excess in Females:
Symptoms Effects Treatment Common Disorder
▪Irregular Menstrual
Periods
▪Hirsutism
▪Acne
▪Male-Pattern Baldness
▪Weight Gain
▪Infertility
▪Emotional distress.
▪Infertility.
▪Metabolic issues like
insulin resistance
▪Medications:
Hormonal medications,
such as birth control
pills or anti-androgen
▪Lifestyle Changes
▪Surgery: In cases of
tumors, surgical
removal may be
necessary.
▪Management: For
conditions like PCOS,
managing insulin
resistance is key.
Polycystic ovary
syndrome (PCOS):
characterized by
hyperandrogenism,
menstrual disturbances
and polycystic ovaries.

25. ➢Androgen Deficiency in Males:
Causes Symptoms Effects Treatment
▪Fatigue
▪Decreased libido
▪Erectile dysfunction
▪Muscle loss
▪Decreased bone
density
▪Mood changes, such
as irritability and
depression
▪Decreased facial and
body hair growth
▪Testicular problems,
such as injury,
infection, or genetic
factors.
▪Age-related: As men
age, their natural
testosterone levels may
decline, leading to
symptoms of androgen
deficiency.
▪Decreased muscle
mass and strength
▪Weaker bones
(osteoporosis)
▪Lower sperm count
and fertility
▪Changes in body
composition, such as
increased fat mass
▪Decreased quality of
life
▪Testosterone
replacement therapy
(TRT) with gels,
injections, or patches
can raise testosterone
levels.
▪Lifestyle changes like
regular exercise, a
balanced diet, and
weight management
may also help.

26. ➢Androgen Deficiency in Females:
Causes Symptoms Effects Treatment
▪Polycystic Ovary
Syndrome (PCOS)
▪Premature Ovarian
Insufficiency
▪Irregular or absent
menstrual periods
▪Excess facial and body
hair (hirsutism)
▪Acne
▪Male-pattern baldness
▪Decreased libido
▪Mood changes
▪Infertility
▪PCOS can lead to
insulin resistance and
an increased risk of
type 2 diabetes.
▪Emotional distress due
to hirsutism and other
visible symptoms.
▪Management of PCOS
may involve birth
control pills, anti-
androgen medications,
or insulin- sensitizing
drugs.
▪Hormone replacement
therapy may be used for
premature ovarian
insufficiency.

27. ❖ Recent Approaches
 Recently, androgen receptor (AR) expression and signaling is widely investigated in
hormone-dependent cancers such as prostate and breast. The incidence and mortality of
these cancers are, however, somewhat related to gender and, specifically, are higher in men
than in women (Sabbatino, 2023).
 Among men, androgens are associated with a decrease in Alzheimer's disease risk.
Research increasingly suggests that changes in estrogen levels during aging may increase
risk for Alzheimer disease, the most common type of dementia. Among women,
genetically determined effects of sex hormones were limited or null. Among men, a higher
concentration of androgens decreased Alzheimer disease risk (Kusters, 2023).
 According to the findings, male patients with COVID-19 infection are at an increased
risk for severe complications than females. This study reveals the role of androgen
receptor in COVID-19 infection (Mjaess, 2020)and (Lott, 2023).

28. ❖ Future Direction
As hormone replacement therapy is treatment for
various hormonal imbalances (excess or deficiency), so,
future researches are concerned about the wide spread
acceptance of the hormone replacement therapy and
development of safe regimes which minimize unwanted
side effects (Vigneswara & Hamoda, 2022).

29. ❖ References
 Elzenaty, R. N., Du Toit, T., & Flück, C. E. (2022). Basics of androgen synthesis and action. Best Practice &
Research Clinical Endocrinology & Metabolism, 36(4),101-665.
 Kusters, C. D., Paul, K. C., Romero, T., Sinsheimer, J. S., & Ritz, B. R. (2023). Among men, androgens are
associated with a decrease in Alzheimer's disease risk. Alzheimer's & Dementia.
 Lott, N., Gebhard, C. E., Bengs, S., Haider, A., Kuster, G. M., Regitz-Zagrosek, V., & Gebhard, C. (2023). Sex
hormones in SARS-CoV-2 susceptibility: key players or confounders?. Nature Reviews Endocrinology, 19(4),
217-231.
 Mjaess, G., Karam, A., Aoun, F., Albisinni, S., & Roumeguère, T. (2020). COVID-19 and the male
susceptibility: the role ofACE2, TMPRSS2 and the androgen receptor. Progrès en urologie, 30(10), 484-487.
 Sabbatino, E., Tutino, V., Licitra, F., Di Donato, M., Castoria, G., Migliaccio, A., & Giovannelli, P. (2023).
Role of the Androgen Receptor in Gender-Related Cancers. Endocrines,4(2), 407-426.
 Vigneswaran, K., & Hamoda, H. (2022). Hormone replacement therapy–Current recommendations. Best
practice & research Clinical obstetrics & gynaecology,81, 8-21.