Clinical Pathology

1. Primary and Secondary
Hypogonadism
K. P. Adewole
UJ/2017/MD/0210

2. Outline
• Introduction
• Definition
• Types
• Primary Hypogonadism
• Definition
• Aetiology
• Pathophysiology
• Clinical Features in Males
• Clinical Features in
Females
• Investigations
• Treatment in Males
• Treatment in Females
• Secondary
Hypogonadism
• Definition
• Aetiology
• Pathophysiology
• Clinical Features in Males
• Clinical Features in
Females
• Investigations
• Treatment in Males
• Treatment in Females
• Conclusion
• References

3. INTRODUCTION
• A failure of the gonads, testes in men and ovaries in
women, to function properly.
• Production of a man's testosterone and a woman's
oestrogen are inhibited.

4. DEFINITION
• Hypogonadism refers to a condition where the
body produces insufficient amounts of sex
hormones, particularly testosterone in males and
estrogen in females.

5. TYPES OF HYPOGONADISM
• Primary Hypogonadism
• Secondary Hypogonadism

6. PRIMARY HYPOGONADISM
• Primary hypogonadism occurs when there is a
dysfunction in the gonads, which are the
reproductive organs responsible for producing sex
hormones.
• In males, the gonads are the testes, and in females,
they are the ovaries.

7. PRIMARY HYPOGONADISM
Aetiology
• Genetic Conditions
• Infections
• Trauma
• Autoimmune Disorders
• Tumors
• Radiation or Chemotherapy
• Aging
• Environmental Factors

8. PRIMARY HYPOGONADISM
Pathophysiology
• Genetic Factors: In cases of genetic conditions (e.g.,
Klinefelter syndrome), there may be abnormalities in
the chromosomes affecting gonadal development and
function.
• Infections and Inflammation: Infections such as
mumps can cause inflammation of the testicles
(orchitis) or ovaries, disrupting normal tissue function
and hormone production.
• Autoimmune Disorders: Autoimmune reactions can
lead to the immune system mistakenly attacking and
damaging gonadal tissues, impairing hormone
synthesis.

9. PRIMARY HYPOGONADISM
Pathophysiology
• Tumors: Tumors in the gonads may interfere with
normal cellular processes, either directly affecting
hormone-producing cells or disrupting the organ's
overall function.
• Trauma: Physical trauma to the testes or ovaries
can result in structural damage, impacting their
ability to produce hormones.
• Toxins and Environmental Factors: Exposure to
certain toxins or environmental factors might
contribute to gonadal damage and dysfunction.

10. PRIMARY HYPOGONADISM
Clinical Features in Males
• Reduced Libido
• Erectile Dysfunction
• Infertility
• Fatigue Muscle Weakness
• Gynecomastia
• Decreased Facial and Body Hair Growth

11. PRIMARY HYPOGONADISM
Clinical Features in Females
• Irregular Menstrual Cycles
• Reduced Fertility
• Hot Flashes
• Vaginal Dryness
• Decreased Breast Size
• Reduced Bone Density

12. PRIMARY HYPOGONADISM
Investigations
• Hormone Levels:
• Testosterone Levels (in Males): Measurement of total and free
testosterone to assess the primary male sex hormone.
• Estrogen and Progesterone Levels (in Females): To evaluate female sex
hormone levels.
• Gonadotropin Levels:
• Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH):
Elevated or decreased levels can provide insights into the type of
hypogonadism (primary or secondary) and potential causes.
• Prolactin Levels: Elevated levels may impact reproductive
function and can be associated with certain types of
hypogonadism.
• Thyroid Function Tests: Hypothyroidism can sometimes coexist
with hypogonadism, and thyroid function should be assessed.

13. PRIMARY HYPOGONADISM
Investigations
• Genetic Testing: In cases of suspected genetic disorders
affecting gonadal function.
• Imaging Studies:
• Ultrasound: To assess the structure of the gonads (testes or
ovaries).
• MRI or CT Scan: To identify any abnormalities in the hypothalamus
or pituitary gland (for secondary hypogonadism).
• Bone Density Measurement: Assessing bone health, as
hormonal imbalances can affect bone density.
• Karyotype Testing: Particularly in cases of suspected
chromosomal abnormalities affecting gonadal development.

14. PRIMARY HYPOGONADISM
Treatment in Males
• Testosterone Replacement Therapy (TRT):
Administering testosterone to bring hormone levels
back to normal.
• Intramuscular Injections, Transdermal Patches, or
Gels: Different forms of testosterone replacement
can be prescribed based on individual preferences
and needs.
• Regular Monitoring: Periodic blood tests to assess
hormone levels and adjust treatment if necessary.

15. PRIMARY HYPOGONADISM
Treatment in Females
• Estrogen and Progesterone Replacement Therapy:
To restore hormonal balance and alleviate
symptoms.
• Hormone Replacement Products: Oral or
transdermal estrogen and progesterone
preparations, depending on the specific needs of
the individual.
• Regular Follow-Up: Monitoring hormone levels and
adjusting treatment as needed.

16. SECONDARY HYPOGONADISM
• Secondary hypogonadism is a condition where the
testes (in men) or ovaries (in women) don't
function properly due to a problem with the
pituitary gland or hypothalamus.

17. SECONDARY HYPOGONADISM
Aetiology
• Hypothalamic Dysfunction
• Pituitary Disorders
• Systemic Illnesses
• Medications
• Nutritional Deficiencies
• Genetic Conditions

18. SECONDARY HYPOGONADISM
Pathophysiology
• Hypothalamic Dysfunction: Conditions affecting the
hypothalamus, such as tumors, trauma, or inflammation,
can disrupt the release of gonadotropin-releasing hormone
(GnRH). GnRH is essential for signaling the pituitary gland to
release luteinizing hormone (LH) and follicle-stimulating
hormone (FSH).
• Pituitary Disorders: Disruptions in the pituitary gland, often
due to tumors, surgery, or radiation, can impair the
secretion of LH and FSH. These hormones are crucial for
stimulating the gonads (testes in men, ovaries in women) to
produce sex hormones (testosterone in men, estrogen in
women).

19. SECONDARY HYPOGONADISM
Pathophysiology
• Reduced Gonadal Stimulation: With decreased LH and
FSH, the gonads receive less stimulation. In men, this
results in reduced testosterone production, leading to
symptoms like low energy, decreased libido, and
fertility issues. In women, it can cause menstrual
irregularities and reduced estrogen levels.
• Impact on Feedback Mechanism: Normally, sex
hormones provide feedback to the hypothalamus and
pituitary to regulate their own production. In secondary
hypogonadism, this feedback loop may be disrupted,
further contributing to hormonal imbalance.

20. SECONDARY HYPOGONADISM
Clinical Features in Males
• Reduced Libido
• Erectile Dysfunction
• Fatigue and Low Energy
• Infertility
• Decreased Muscle Mass
• Increased Body Fat
• Mood Changes

21. SECONDARY HYPOGONADISM
Clinical Features in Females
• Irregular Menstrual Cycles
• Hot Flashes
• Vaginal Dryness
• Reduced Libido
• Bone Density Loss
• Mood Changes

22. SECONDARY HYPOGONADISM
Investigations
• Hormone Testing: Blood tests to measure hormone
levels, including testosterone (in men), estrogen and
progesterone (in women), luteinizing hormone (LH),
and follicle-stimulating hormone (FSH). Abnormal levels
can indicate dysfunction in the hypothalamic-pituitary-
gonadal (HPG) axis.
• Prolactin Levels: Elevated levels of prolactin can
interfere with the normal functioning of the HPG axis.
• Thyroid Function Tests: Thyroid dysfunction can
contribute to reproductive hormone imbalances

23. SECONDARY HYPOGONADISM
Investigations
• Imaging Studies: MRI or CT scans may be performed to
evaluate the hypothalamus and pituitary gland for any
structural abnormalities, such as tumors.
• Bone Density Test (DEXA Scan): Especially in women,
assessing bone density can provide insights into the
impact of hormonal deficiencies on bone health.
• Genetic Testing: In some cases, genetic testing may be
recommended to identify underlying genetic conditions
affecting the reproductive system.

24. SECONDARY HYPOGONADISM
Treatment in Males
• Testosterone Replacement Therapy (TRT): This involves
administering testosterone to bring levels back to normal.
Various forms are available, including injections, patches,
gels, and pellets. The choice depends on individual
preferences and medical considerations.
• Monitoring and Adjustments: Regular monitoring of
testosterone levels and symptoms is crucial. Dosage
adjustments may be needed to maintain optimal hormone
levels and address any side effects.
• Fertility Preservation: For those concerned about fertility,
alternative treatments such as human chorionic
gonadotropin (hCG) or selective estrogen receptor
modulators (SERMs) might be considered to stimulate
natural testosterone production.

25. SECONDARY HYPOGONADISM
Treatment in Males
• Lifestyle Modifications: Encouraging a healthy lifestyle with
regular exercise, a balanced diet, and adequate sleep can
complement hormone therapy and improve overall well-
being.
• Management of Underlying Causes: Addressing any
underlying causes, such as pituitary tumors or other medical
conditions, is essential for comprehensive treatment.
• Patient Education and Counseling: Providing information
about treatment options, potential side effects, and the
importance of adherence is crucial. Counseling may also
address psychological aspects related to the condition.

26. SECONDARY HYPOGONADISM
Treatment in Females
• Hormone Replacement Therapy (HRT): Estrogen replacement
therapy is often used to address low estrogen levels. It can be
administered through oral pills, patches, creams, or vaginal
rings. Progestin may be included if a woman has an intact
uterus to prevent the risk of endometrial hyperplasia.
• Fertility Treatments: For women desiring fertility,
interventions such as gonadotropin therapy or in vitro
fertilization (IVF) may be considered, depending on the specific
hormonal imbalances.
• Bone Health Management: Since estrogen plays a role in
maintaining bone density, calcium and vitamin D supplements,
along with weight-bearing exercises, may be recommended to
support bone health.

27. SECONDARY HYPOGONADISM
Treatment in Females
• Management of Menopausal Symptoms: For women
experiencing menopausal symptoms such as hot flashes
or vaginal dryness, HRT can be tailored to address these
specific symptoms.
• Lifestyle Modifications: Encouraging a healthy lifestyle,
including regular exercise, a balanced diet, and stress
management, can contribute to overall well-being.
• Monitoring and Adjustments: Regular follow-up visits
are crucial to monitor hormone levels and adjust
treatment as needed. This ensures that hormonal
balance is maintained while minimizing potential risks.

28. CONCLUSION
• Hypogonadism occurs when the sex glands produce
little to no sex hormones.
• The sex glands, also called gonads, are primarily the
ovaries in females and the testes males.
• Symptoms can include fatigue, reduced libido, and
reproductive issues.
• Treatment options vary and may involve hormone
replacement therapy.

29. REFERENCES
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Testosterone therapy in men with androgen deficiency
syndromes: an Endocrine Society clinical practice guideline.
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(2016) Williams Textbook of Endocrinology. 13th ed.
Philadelphia, PA: Elsevier; 2019.
• Rosenfield RL, Wernze H. (2018) Hypogonadism in the male
and female. In: Kliegman RM, Stanton BF, St. Geme JW,
Schor NF, Behrman RE, eds. Nelson Textbook of Pediatrics.
21st ed. Philadelphia, PA: Elsevier; 2019:chap 583.
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