Nweke Favour

Edo State College of Nursing Sciences,

Godwin Abbey Way,
Off Sapele Road,
Benin City.
20th October, 2024.

Osagie Lucky
14 Goodnews Avenue,
Off Upper Mission Road,
Benin City.
Dear Mr.Lucky
LETTER OF ENQUIRY RESPONSE
Thank you for your enquiry regarding our Nursing Program at Edo State College Of
Nursing sciences, dated 01 June 2024 at 10:05am. We appreciate your interest in
our institution.
We offer the following nursing program such as bachelor of Science in Nursing
(BSN), Associate Degree in Nursing (ADN), Lincensed Practical Nurse (LPN) and
National Diploma Nursing (NDN).
These are the admission requirement: Provide official transcripts, submit letter of
Recommendation and sponsorship and meet the minimum GPA of 2.5. Application
process, visit the school website at edocns.ng.com, fill the online application form
and upload your require documents.
If you have any further questions or concerns, please do not hesitate to contact us.
THANK YOU.
Sincerely,
Nweke Favour.
Nweke Favour
14b Goodnews Avenue,
Off Upper Mission Road,
Benin City,
Favourcosta14@gmail.com
08101245576
20th October, 2024.

The Facility Officer,

University of Benin Teaching Hospital,
Ugbowo Lagos Road,
Benin City.
Dear Sir/ma
LETTER OF ENQUIRY TO HEALTH CARE AGENCY
I am writing this letter with the intention to get some information about your health
care agency. Recently, I have heard about your health care agency, and I came to
know that you are providing good quality services here. So, I want to know some
more details about it.
It will be very kind of you if you provide me the details about health care package.
I will love to ask few question, what are the best facilities your agency provides to
common people? Diseases conditions which are treated in your agency? How much
it costs to get the treatment in your health care agency? Does this agency provide
health insurance?
I will be expecting your quick response. Please contact me through the listed phone
number or email address. THANK YOU.
Sincerely,
Nweke Favour
Nweke Favour
14b Goodnews Avenue,
Off Upper Mission Road,
Benin City,
20th October, 2024.

Edo Specialist Hospital,

The Director of Nursing,
Sapele Road,
Benin City.
Dear Director
LETTER OF RECOMMENDATION
It is with pleasure that I write to letter of recommend Ms. Debbie Hughes, who has
served with me in my role as Medical Director at Ohio Department of Mental Health
on the Department's All Hazards Leadership Initiative in the Integrated Behavioral
Healthcare Systems division.
Debbie is a conscientious and dependable employee. She is professional in her
work and gets along well with coworkers and others. Debbie's position requires an
understanding of numerous All Hazards Preparedness entities and partnerships.
She has consistently performed well, has demonstrated leadership in this role and
thrives on new challenges, she is a team player.
At Ohio Department Mental Health, she has participated in several projects and
team tasks with good results. I feel strongly that you will find Debbie to be a valued
employee who can contribute to your agency.
I look forward to receive a respond from you. THANK YOU.
Sincerely,
Nweke Favour.
Nweke Favour
14b Goodnews Avenue,
Off Upper Mission Road,
Benin City,
20th October, 2024.

The Manager,
Nadia Bakery,
Ugbowo Lagos Road,
P.O Box 300103.

Dear Sir/ma
LETTER OF COMPLAINT
I am writing to express my extreme dissatisfaction and frustration with the services
at your company, I brought meat pie from Nadia Bakery dated 12th October 2024
on my birthday and sad to say, I am not content with the meat pie given to me.
This is the first time that I came across such trouble from your company, so I believe
that this is a one-time event, and that it is not a representation of your company's
quality. I hope you will address this matter seriously.
Due to this, I am hoping for an intervention from your good office, and sort out this
issue immediately. I have already been inconvenienced enough as it is, and I want
this matter to be resolved as quickly as possible. I am hoping to receive a good meat
pie on my next visit. THANK YOU

Sincerely,
Nweke Favour.
Nweke Favour
14b Goodnews Avenue,
Off Upper Mission Road,
Benin City,
20th October, 2024.

Edo Specialist Hospital,

The Director of Nursing,
Sapele Road,
Benin City.
Dear Ms Martha
LETTER OF RESIGNATION
I am writing to you this letter as notice of resignation as Staff Nurse of Edo Specialist
Hospital, effective 05/11/2024. This decision isn't easy for me to make.
I will be travelling the country to Canada by December 2024 my visa is out, I have
decided to advance my studies over there and have gotten a new job which will
require my full attention and for completion in the university that I have chosen.
I enjoyed my time at Edo Specialist Hospital, During my tenure, I have learned a
tremendous amount of knowledge and skills to work efficiently in my position. I
know as well that these skills can be utilized in my future endeavors. I will forever
appreciate the opportunity given to me here and I want to thank you for it.
With my remaining days in Edo Specialist Hospital, I will gladly help in any way I
could be of help to make the transition easier. If there is anything I can do to be of
assistance, please let me know. I look forward to staying in contact with you in the
future. THANK YOU
Sincerely,
Nweke Favour
Nweke Favour
14b Goodnews Avenue,
Off Upper Mission Road,
Benin City,
20th October, 2024.

The Gynecologist,
Edo Specialist Hospital,
Sapele Road,
Benin City.

Dear Doctor Nosa

LETTER OF APPRECIATION
I am writing to express my sincere gratitude and appreciation for the care and
attention you and your team have render to me during this difficult time. You have
gone above and beyond to ensure my good health and well-being throughout this
difficult period.
From the initial diagnosis to the follow-up treatments and beyond, you have always
been able to provide me with the utmost level of care and compassion.
Your attention to detail and dedication to my health is something I will always be
thankful for. No matter the hour, you have always ensured that I was taken care of,
and nothing has been overlooked.
On behalf of myself and my family, I would like to thank you for all the work you
have done. Your efforts have been instrumental in my recovery and I
wholeheartedly appreciate everything you have done. THANK YOU.
Sincerely,
Nweke Favour.
Nweke Favour
14b Goodnews Avenue,
Off Upper Mission Road,
Benin City,
20th October, 2024.

The Manager,
Nadia Bakery,
Ugbowo Lagos Road,
P.O Box 300103.

LETTER OF INCIDENT REPORT

On October 20,2024, at approximately 14:45, Jane Smith slipped and fell on the wet
floor in the break room. The incident occurred when Jane was walking to the
vending machine and lost her balance due to the slippery surface.
Jane suffered minor injuries, including bruises on her left arm and right knee. First
aid was administered by the onsite medical staff, the area was secured and cleaned
to prevent further complications. She was taken to hospital close to the office for
further medical evaluation.
The incident has been documented and investigated, recommendations have been
made to prevent similar incidents from occurring in the future. A follow up meeting
will be held on second week of November to review the status of the active plan.
THANK YOU.
Sincerely,
Nweke Favour.
Nweke Favour
14b Goodnews Avenue,
Off Upper Mission Road,
Benin City,
20th October, 2024.

17 Goodnews Avenue,
Off Upper Mission Road,
Benin City.

Dear Mr Monday
LETTER OF INVITATION
I am writing to invite you personally to take part in the work of a new Group that
the Commission is bringing together. The aim is to improve top-level official
coordination among EU members on a broad range of health issues. I have been
asked by Commissioner Byrne to chair the process, and I would be very pleased if
you would join me in launching our work, in Brussels on 30th November.
In order for cooperation to be effective and to respect the responsibilities of the
Member States for health services and medical care, this Group will depend on the
active engagement of the senior officials responsible for these issues from Member
States.
The Group should, with your support, be able to bring two important changes to
what we have done together so far: first, to raise the level of our cooperation on a
sustained basis, and second to ensure that we are all working together on a broader
set of issues than in the past. I will really appreciate your presence, hope to see you
soon. THANK YOU
Sincerely,
Nweke Favour.
Nweke Favour
14b Goodnews Avenue,
Off Upper Mission Road,
Benin City,
Favourcosta14@gmail.com
20th October, 2024.

Dr. Liam Troy,

Specialist Hospital,
Sapele Road,
Benin City.

Dear Dr. Troy,

LETTER OF REQUEST
I am writing to request a medical certificate on behalf of an employee. The
employee, Kenneth Earl, who is currently under my care, requires the certificate
for medical leave documentation purposes. It would be greatly appreciated if you
could kindly provide the necessary medical certificate.
I understand the importance of such certificates in ensuring the proper
documentation and support for the employee's medical condition. Your kind
assistance in this matter is valuable and highly appreciated. THANK YOU
Sincerely,
Nweke Favour.
Nweke Favour
14b Goodnews Avenue,
Off Upper Mission Road,
Benin City,
Favourcosta14@gmail.com
20th October, 2024.

Edo Specialist Hospital,

The Director of Nursing,
Sapele Road,
Benin City.
Dear Madam
LETTER OF APPLICATION

I am writing to apply for the post of a staff nurse staff in Edo Specialist Hospital
which was advertised on ITV and NTA dated 20th October 2024.
With my 5 years of experience in medical and surgical nursing which give me the
proper knowledge of patient evaluation and intervention at a minimal time, I am
an expert in supporting licensed pharmacists in a fast-paced environment,
preparing and packaging medication orders, maintaining customer records, and
handling the medication inventories.
I felt the position suit me as I will add a great value to your already established
team. Below is my attached CV which you can take your time to go through. I am
looking forward to get a response from you and working with your great team.
THANK YOU.
Sincerely,
Nweke Favour.
 SPERMATOGENESIS

Spermatogenesis is a process of developing male gametes, known as sperm within the

male reproductive organs, the testes. In this process, each sperm (haploid,
containing a single copy of each chromosome. In order to create the haploid gamete, a
cell undergoes the process of meiosis in which the genome is replicated and divided twice
to produce four haploid gametes.
This process generally occurs in the seminiferous tubules of the testes following different
stages. It is followed by maturation in the epididymis where they are secreted in the form
of semen along with glandular secretions. This process begins during puberty and ends
only when the individual dies. The complete process of spermatogenesis in males are
carried out by the actions of Leydig cells, hypothalamus, and pituitary gland The quantity
of these sperms gradually reduces with the age and finally leads to infertility.

Spermatogenesis is the complex process by which immature cells (spermatogonia)

develop into mature sperm cells (spermatozoa) in the male reproductive system. This
process is essential for male fertility and reproduction.
Spermatogenesis is the process by which immature cells (spermatogonia) develop into
mature sperm cells (spermatozoa) in the male reproductive system.
STAGES OF SPERMATOGENESIS

Spermatogenesis is divided into three main stages:

Stage 1: Spermatocytogenesis (Proliferation)

1. Spermatogonia (diploid) proliferate and differentiate into:

2. Primary spermatocytes (diploid)

3. Occurs in seminiferous tubules

Stage 2: Meiosis (Reduction Division)

1. Primary spermatocytes undergo meiosis I, resulting in:

2. Secondary spermatocytes (haploid)

3. Secondary spermatocytes undergo meiosis II, resulting in:

4. Spermatids (haploid)

Prophase I → Metaphase I → Anaphase I → Telophase I

Prophase II → Metaphase II → Anaphase II → Telophase

MEIOSIS

DEFINITION: Meiosis is a specialized type of cell division that reduces the chromosome
number by half, resulting in the production of gametes (sperm or egg cells) with unique
combinations of genetic traits.

TYPE OF MEIOSIS

1. Meiosis I (Reduction Division)

2. Meiosis II (Equational Division)

Meiosis I:

1. Prophase I: Chromosomes condense, homologous pairs form, and crossing over

occurs.

2. Metaphase I: Homologous pairs align at the equator.

3. Anaphase I: Homologous pairs separate.

4. Telophase I: Nuclear envelope reforms.

Meiosis II:

1. Prophase II: Chromosomes condense.

2. Metaphase II: Sister chromatids align at the equator.

3. Anaphase II: Sister chromatids separate.

4. Telophase II: Nuclear envelope reforms.

Key features

1. Reduction of chromosome number (diploid to haploid)

2. Crossing over (genetic recombination)

3. Independent assortment (random alignment of chromosomes)

4. Unique gametes produced

Importance:

1. Genetic diversity

2. Increased variability

3. Evolutionary adaptation

4. Fertility and reproduction

Errors in Meiosis:

1. Nondisjunction (failure of chromosome separation)

2. Aneuploidy (abnormal chromosome number)

3. Genetic disorders (e.g., Down syndrome)

Meiosis in Humans:

1. Occurs in reproductive cells (sperm and egg cells)

2. 23 pairs of chromosomes reduced to 23 haploid chromosomes

3. 46 chromosomes in diploid cells reduced to 23 in haploid gamete

Stage 3: Spermiogenesis (Differentiation)

1. Spermatids undergo differentiation, acquiring:

2. Acrosome (enzyme-containing vesicle)

3. Flagellum (tail)

4. Nuclear condensation

5. Spermatozoa formation.

Stage 4: Maturation

1. Spermatozoa mature in epididymis

2. Acquire motility and fertilization ability

3. Final shaping and maturation of spermatozoa

DEFINITION

Maturation is the final stage of spermatogenesis, where spermatozoa acquire motility,

fertilization ability, and mature morphology.

Stages of Maturation

1. Spermatozoa formation

2. Nuclear condensation

3. Acrosome formation

4. Flagellum development

5. Cytoplasmic reduction

6. Maturation in epididymis
Epididymal Maturation

1. Spermatozoa migrate to epididymis

2. Acquire motility and fertilization ability

3. Undergo capacitation (pre-fertilization changes)

Changes During Maturation

1. Nuclear shape and size

2. Acrosome formation and stabilization

3. Flagellum development and motility

4. Cytoplasmic reduction and elimination

5. Plasma membrane changes

Importance of Maturation

1. Fertilization ability

2. Motility and movement

3. Sperm-egg interaction

4. Embryonic development

Factors Affecting Maturation

1. Hormones (testosterone, FSH)

2. Temperature

3. pH and ionic balance

4. Oxidative stress

5. Epigenetic regulation

Detailed Stages of Spermatogenesis:

1. Spermatogonial proliferation
2. Spermatogonial differentiation

3. Meiosis I

4. Meiosis II

5. Spermiogenesis

6. Acrosome formation

7. Flagellum formation

8. Nuclear condensation

9. Spermatozoa formation

10. Maturation

Regulation of Spermatogenesis

- Hypothalamic-pituitary-gonadal axis.

- Testosterone and follicle-stimulating hormone (FSH).

- Inhibin and activin.

Factors Affecting Spermatogenesis

- Age

- Hormonal imbalances

- Temperature (heat, radiation)

- Toxins (chemicals, pesticides)

- Genetic disorders

- Infections (epididymitis, orchitis)

- Trauma or surgery

Disorders Related to Spermatogenesis

- Male infertility
- Azoospermia (no sperm)

- Oligospermia (low sperm count)

- Asthenospermia (reduced motility)

- Teratospermia (abnormal morphology)

Diagnostic Tests

- Semen analysis

- Hormone testing (FSH, LH, testosterone)

- Genetic testing (karyotyping, Y-chromosome microdeletion)

- Imaging studies (ultrasound, MRI)

Treatment Options

- Hormone therapy

- Medications (clomiphene, letrozole)

- Assisted reproductive technologies (ART)

- Surgery (varicocele repair, vasectomy reversal)

Conclusion

Spermatogenesis is a complex process essential for male fertility. Understanding the

stages, regulation, and factors affecting spermatogenesis can aid in diagnosis and
treatment of related disorders
 MENOPAUSE
Menopause is a point in time when you’ve gone 12 consecutive months without
a menstrual period. It happens, on average, at age 52. It’s a natural process that occurs
when your ovaries stop producing reproductive hormones. When menopause happens
due to surgery or medical treatment, it’s called induced menopause.

Menopause is the permanent ending of menstruation. If it doesn’t happen because of any

type of medical treatment or surgery, the process is gradual and happens in three stages:

STAGES OF MENOPAUSE

Perimenopause or “menopause transition:” Perimenopause can begin eight to

10 years before menopause when your ovaries gradually produce less and less
estrogen. It usually starts when you’re in your 40s. You can be in perimenopause
for several months or several years. Many people begin feeling symptoms like
irregular periods, hot flashes and mood swings in perimenopause.

Menopause: Menopause is the point when you no longer have menstrual periods.
At this stage, your ovaries don’t release eggs, and your body doesn’t produce
much estrogen. A healthcare provider diagnoses menopause when you’ve gone
without a period for 12 consecutive months. Unlike the other stages, menopause
itself is a defined moment, so you don’t stay in this stage.

Postmenopause: This is the time after menopause. You stay in postmenopause

for the rest of your life. While most symptoms of menopause ease up in
postmenopause, you can continue to have mild menopausal symptoms for several
years in postmenopause. People in the postmenopausal phase are at an increased
risk for osteoporosis and heart disease due to low estrogen levels.

SIGNS AND SYMPTOMS

 Irregular periods or periods that are heavier or lighter than usual.
 Hot flashes, also known as vasomotor symptoms (a sudden feeling of warmth that
spreads over your body).
 Night sweats and/or cold flashes.
  Vaginal dryness that causes discomfort during sex.
 Urinary urgency (a pressing need to pee more frequently).
 Difficulty sleeping (insomnia).
 Emotional changes (irritability, mood swings or depression).
 Dry skin, dry eyes or dry mouth.
 Worsening premenstrual syndrome (PMS).
 Breast tenderness.
 Racing heart.
 Headaches.
 Joint and muscle aches and pains.
 Changes in libido (sex drive).
 Difficulty concentrating or memory lapses (often temporary).
 Weight gain.
 Hair loss or thinning.

CAUSES OF MENOPAUSE
 Natural decline of hormones. As you enter your late 30s, your ovaries start
making less of the hormones that control your period. These are called estrogen and
progesterone. With lower levels of them, it's harder to get pregnant.
In your 40s, your menstrual periods may get longer or shorter, heavier or lighter,
and happen more often or less often. In time, your ovaries stop releasing eggs.
Then you have no more periods. This happens on average around age 51.
 Surgery that removes the ovaries, called oophorectomy. Ovaries make
hormones, including estrogen and progesterone, that control the menstrual cycle.
Surgery to remove the ovaries causes instant menopause.
Your periods stop. You're likely to have hot flashes and other menopausal
symptoms. Symptoms can be severe because the surgery causes hormones to drop
all at once rather than slowly over several years.
Surgery that removes the uterus but not the ovaries, called hysterectomy, most
often doesn't cause instant menopause. You no longer have periods. But your
ovaries still release eggs and make estrogen and progesterone for a time.
 Chemotherapy and radiation therapy. These cancer therapies can cause
menopause. They can cause symptoms such as hot flashes during or shortly after
 treatment. Periods sometimes return after chemotherapy. Then you can still get
pregnant. So you might want to keep using birth control.
Radiation therapy aimed at the pelvis, belly and lower spine can cause
menopause. Radiation to the whole body for stem cell transplant also can cause
menopause. Radiation therapy to other parts of the body, such as breast tissue or
the head and neck, likely won't affect menopause.
 Primary ovarian insufficiency. About 1% of people who have menopause get it
before age 40. This is called premature menopause. Premature menopause may
result from the ovaries not making the usual levels of hormones. This is called
primary ovarian insufficiency.
Often no cause of premature menopause can be found. Then healthcare
professionals most often suggest hormone therapy. Taken at least until the typical
age of menopause, hormone therapy can protect the brain, heart and bones.

MANAGEMENT AND TREATMENT

Menopause is a natural process that your body goes through. In some cases, you
may not need any treatment for it. When discussing treatment for menopause with
your healthcare provider, it’s about treating the symptoms of menopause that
disrupt your life. There are many different types of treatments for managing
menopause symptoms. The main types are:

Hormone therapy (HT). A term used for hormones offered to those going through
menopause at natural ages (after age 45).

Hormone replacement therapy (HRT). The word replacement is added when

using hormones to treat menopause which occurs at a young age, especially
before age 40.

Nonhormonal treatments: It’s important to talk to your provider while you’re going
through menopause to craft a treatment plan that works for you. Every person is
different and has unique needs. People experiencing menopause before age 40
should be offered hormone replacement therapy, except in rare circumstances
(such as a personal history of breast cancer at a young age).
ANDROPAUSE
Andropause or male menopause is the term used to describe reducing levels of
testosterone due to hormonal changes in men as a result of ageing. This is, however, a
completely different situation from that of menopause in women. In women, menopause
brings about a complete end to ovulation over a relatively shorter period of time. In men,
on the other hand, the decreased testosterone levels and hormone production occurs
more gradually. Medical professionals may use the term ‘Late Onset Hypogonadism’ for
extremely low levels of male hormones.

Once you cross the age of 30, there will be a slow decline in testosterone by
approximately 1% each passing year. This means that the testes do not completely stop
producing testosterone. However, as a result of diabetes and certain other factors
mentioned below, there could be minutely noticeable changes in the function of the testes
between 45 to 50 years of age.

SIGNS AND SYMPTOMS

Age is the most common factor that contributes to andropause. Once a man crosses 70
years of age, he may experience up to a 50% decline in testosterone levels. Other factors
that can cause lower testosterone levels are: obesity, type 2 diabetes, hormonal
disorders, liver or kidney disease, and infections. Common symptoms of andropause
include:

 Increase in body fat

 Erectile dysfunction
 Decreased libido (low sex drive)
 Disturbance in sleep patterns
 Thinning of skin
 Dryness of skin
 Mood swings and Irritability
 Depression
 Lack of energy
 Hot flushes
 Muscle mass reduction
 Reduced ability in concentrating
 Excessive sweating or Hyperhidrosis
  infertility

It is important to note that signs and symptoms of andropause can differ from person to
person. Men who experience male menopause also have an increased risk of developing
certain complications like osteoporosis and cardiovascular problems.
CAUSES OF ANDROPAUSE

Your testosterone levels are low before you hit puberty. As you age sexually, the levels
increase. Testosterone is the hormone that governs the various stages of male puberty.
The causes of andropause are:

Andropause, or male menopause, occurs due to:

1. Ageing: Testosterone production declines with age, typically starting around 30.
2. Hormonal changes: Decreased testosterone, alongside alterations in other
hormones like LH and FSH, contributes to andropause.
3. Lifestyle: Factors such as poor diet, lack of exercise, stress, substance abuse,
and smoking can worsen symptoms.
4. Chronic conditions: Obesity, diabetes, cardiovascular disease, and sleep apnea
can prepone andropause symptoms.
5. Genetics: Family history may influence the timing and severity of andropause.
6. Psychological factors: Depression, anxiety, and low self-esteem can impact
hormone levels and worsen symptoms.

Diagnosis, Treatment And Prevention Of Andropause

Andropause is generally diagnosed by an urologist or a male fertility expert (Andrologist),
by way of a physical examination and detection of accompanying symptoms. The medical
expert may also order a few diagnostic tests to figure out whether the condition is due
to any medical problem, followed by blood tests to measure testosterone levels of the
patient.

Symptoms associated with male andropause are potentially treatable. However, to

reverse the decline in testosterone levels, certain lifestyle changes will be recommended.
This could be a combination of an exercise program and dietary changes. Medication or
testosterone replacement therapy might be suggested in selected cases, but it is known
to have some harmful side effects. The pros and cons of hormone injections can be
discussed with your doctor.
 CONCLUSION
It’s quite normal for men to experience a decline in testosterone levels as they age.
Although many can cope with the symptoms without treatment, if your symptoms are
proving problematic, it’s important to consult your doctor. Don’t hesitate to talk to them,
as they can provide recommendations on how to manage or treat your symptoms.

PUBERTY
Puberty is the process of physical maturation where an adolescent reaches sexual
maturity and becomes capable of reproduction. On average, puberty typically begins
between 8 and 13 in females and 9 and 14 in males. Puberty is associated with emotional
and hormonal changes, as well as physical changes such as breast development in
females (thelarche), pubic hair development (pubarche), genital changes in males, voice
changes, an increase in height, and the onset of menstruation (menarche). Puberty
proceeds through five stages, termed Tanner stages, ranging from prepubertal, to full
maturity.

DEVELOPMENT

Female Development During Puberty

1. Thelarche: Thelarche refers to breast growth, typically the first sign of puberty in
girls, occurring around 9 or 10. An increase in estrogen causes the lactiferous duct system
to develop, while an increase in progesterone causes the lobular alveoli at the ends of
lactiferous ducts to increase in number.

2. Pubarche: Approximately six months after thelarche begins, pubarche, or growth of

pubic hair, will typically occur. Pubic hair initially appears light, sparse and straight but
will become coarse, thick, and dark throughout the course of puberty. Approximately two
years after pubarche, axillary hair will begin to grow, a secondary sexual characteristic
mediated by testosterone.
3. Menarche: Menarche is the female's first menstrual period, caused by an increase in
FSH and LH. Menarche typically occurs 1.5 to 3 years after thelarche at approximately
12.8 years of age in White race girls and 3-8 months later in African-American girls.
During puberty, the uterine endometrium undergoes cycles of proliferation and regression
due to fluctuating plasma estradiol levels. This occurs until a point is reached when
substantial growth occurs so that withdrawal of estrogen results in the first menstruation
(menarche). Plasma progesterone levels remain low until a rise occurs after menarche,
indicating that ovulation has occurred. The first ovulation takes place approximately 6 to
9 months after menarche due to an immature positive feedback mechanism of estrogen.

4. Ovarian Development: The rise in gonadotropins during puberty stimulates the

ovary to produce estradiol, which is responsible for developing secondary sexual
characteristics such as thelarche, growth of reproductive organs, fat redistribution to the
hips and breasts, and bone maturation. Ovarian size increases from prepubertal volume
(approximately 0.5 cm^3) to a postpubertal volume (approximately 4.0 cm^3).

5. Uterus Size: The uterus of a prepubertal female is tear-drop shaped, with the neck
and isthmus accounting for up to two-thirds of the uterine volume. An increase in
estrogen production causes the uterus to become pear-shaped, with the uterine body
increasing in length and thickness.

6. Vaginal Changes: Puberty brings about an enlargement of the labia major and labia
minora. Clear to white vaginal discharge may also be seen prior to the onset of menarche.

Male development during puberty

1. Testicular Size: An increase in testicular size is typically the first sign of puberty in
boys. Testes increase in size during puberty due to the development of the seminiferous
tubules. Increased LH stimulates the synthesis of testosterone by Leydig cells, while
increased FSH stimulates the production of sperm by Sertoli cells. Testicular size increases
throughout puberty up to Tanner stage 4, at which time the adult longitudinal diameter
and volume are reached. An increase in testicular size causes the scrotal skin to become
thinner and darker in color. Boys typically experience their first ejaculation approximately
one year after the testicles begin to grow. The first ejaculation, however, does not
automatically signal an ability to procreate. On average, fertility is achieved one year after
the first ejaculation.

2. Pubarche: The growth of pubic hair at the penile base typically occurs alongside
testicular development. Pubic hairs initially appear light, straight and thin; then become
darker, curlier, and thicker as puberty progresses. Approximately two years after the
onset of pubarche, axillary, chest, and facial hair begin to grow.

3. Penis Size: The growth of the penis occurs after testicular enlargement. The penis
grows in length, then width, and the glans penis and corpus cavernosum also enlarge.

GROWTH SPURT

The growth spurt results from interactions between sex steroids (estradiol/testosterone),
growth hormone, and IGF-1. The rise in sex steroids leads to an increase in growth
hormone levels, which causes an increase in IGF-1. IGF-1 causes somatic growth via its
metabolic actions (e.g., increases trabecular bone growth). Following the growth spurt in
males, the larynx and vocal cords enlarge, and the boy's voice may 'crack' as it deepens
in pitch.

ADRENARCHE

Adrenarche refers to the increased secretion of adrenal androgen precursors

dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and
androstenedione from the adrenal zona reticularis, which typically occurs prior to puberty
in children around the ages of 6-8 years. The eventual phenotypical result of adrenarche
is pubarche, as well as apocrine odor, increased oiliness of hair and skin, and acne.

PATHOPHYSIOLOGY
The pathophysiology of puberty can be broken down into three main categories:
premature (precocious) puberty, delayed puberty, and contrasexual development.

Precocious Puberty

Precocious puberty, or early development of secondary sexual characteristics, is defined

as the appearance of secondary sexual characteristics prior to the age of eight in girls or
before the age of nine in boys. Precocious puberty can be broken down by pathological
location into central or peripheral precocious puberty. Central precocious puberty (CPP)
involves activation of the hypothalamic-pituitary-gonadal (HPG) axis, which leads to early
but normal pubertal development. CPP is more common in girls, and while most cases
are idiopathic, it can be caused by neoplasm, radiation, head trauma, or genetic
conditions. Peripheral precocious puberty (PPP) results from an increase in sex steroids
that does not come from activation of the HPG axis. Findings in PPP patients typically
include a rapid and atypically sequenced pubertal progression. The most notable causes
of PPP include McCune-Albright syndrome and testotoxicosis.

Many causes of early pubertal development are shared among girls and boys; however,
some causes of early puberty are unique to each of the sexes. The causes of precocious
puberty shared by either gender include benign premature adrenarche, central nervous
system (CNS) and pituitary lesions, constitutional and idiopathic precocious puberty,
McCune-Albright syndrome, and exogenous sex hormones.

 Premature adrenarche correlates with the premature presence of pubic or

axillary hair and possibly increased sebaceous gland activity, without other signs
of puberty present, usually before six years of age. This is typically an isolated
abnormality, and most children go on to develop the other signs of puberty at a
normal age. Plasma DHEAS is usually elevated to pubertal levels, while FSH, LH,
estradiol, and testosterone are typically at levels found in prepubertal children.
Other studies, such as a GnRH stimulation test, will show prepubertal results. An
ACTH stimulation test may help exclude congenital adrenal hyperplasia, which may
present with similar symptoms.
 CNS and pituitary lesions will typically present with normal but early occurring
stages of puberty, and children may present with a bone age greater than their
chronological age. Additionally, these lesions may cause other problems to
develop, such as visual field defects. If a CNS or pituitary lesion is suspected, an
MRI of the brain should be ordered to confirm or rule out this diagnosis.
 Constitutional/idiopathic precocious puberty can occur in males and
females but tends to be more prevalent in females. Precocious or premature
puberty is considered idiopathic when a child has no familial links to premature
development, and there is no other cause that explains the premature
development of puberty. Constitutional precocious puberty can be linked to a
familial tendency toward early development. Children with these disorders will
respond to a GnRH stimulation test with pubertal levels of sex hormones, including
FSH and LH. These children may have a bone age that is much higher than their
chronological age. Additionally, all other causes of premature puberty must be
ruled out, such as CNS pathology and elevated adrenal hormones.
 McCune-Albright Syndrome is associated with cafe-au-lait spots, polyostotic
fibrous dysplasia, precocious puberty, and may be associated with other endocrine
disorders. Precocious puberty seen in McCune-Albright syndrome manifests in
early childhood, with sudden onset vaginal bleeding typically the initial sign of the
condition. Individuals may begin to experience vaginal bleeding as early as two
years of age.
  Exogenous sex hormones in substances such as oral contraceptives and
anabolic steroids can cause secondary sexual characteristics to develop. These
causes can usually be ruled in or out rather quickly by performing a urinalysis, as
the metabolites of exogenous hormones can be found in the urine. Additionally,
children who have an exogenous hormone source and are not undergoing natural
puberty will lack pubic hair. Girls may have darkened areolas, and boys will have
small testicles resembling the size of a prepubertal child.

Causes of premature puberty unique to males include gonadotropin-secreting

tumors and testotoxicosis.

 Gonadotropin-secreting tumors typically secrete hCG-like components that

can have a similar function in signaling to LH, resulting in an incomplete type
of premature puberty in boys. Girls, however, need FSH to increase estrogen
production in the ovaries and thus, will not have premature development due to
this type of tumor alone. Examples of tumors that might produce hCG are
hepatomas, teratomas, and germinomas of the pineal gland.

 Testotoxicosis is a cause of peripheral precocious puberty in which boys present

with early-onset puberty between 2 and 4 years of age. Patients experience early
development of secondary sexual characteristics, accelerated growth, and
diminished adult height. The cause of testotoxicosis is linked to a heterogenous
constitutively activating mutation of the LHCGR gene encoding the luteinizing
hormone receptor. Laboratory analysis will show an increased level of sex steroids
in the setting of low LH levels.

Delayed Puberty

Delayed puberty is the lack of physical evidence of puberty by 2 to 2.5 standard deviations
above the mean age for the initiation of puberty. In boys, this is considered a period
longer than four years between the first signs of testicular enlargement and the end of
puberty or the absence of testicular growth by 14 years old. Delayed puberty in girls is
considered the absence of breast growth by 13 years of age or more than four years
between thelarche and menarche. The causes of delayed puberty include
hypogonadotropic hypogonadism, hypergonadotropic hypogonadism, hypopituitarism,
chromosomal abnormalities, and hypothalamic dysfunction due to secondary causes.

 Hypogonadotropic hypogonadism is due to a hypothalamus or pituitary gland

disorder, resulting in GnRH, LH, or FSH deficiency. Several causes of
hypogonadotropic hypogonadism exist, including damage to the hypothalamus or
 pituitary gland from surgery, tumor, infection, or injury. Genetic defects, severe
stress, and long-term use of opioids or glucocorticoids can also be a cause.
Additionally, nutritional problems and iron overload may also cause
hypogonadotropic hypogonadism.
 Constitutional delay of growth and puberty is a transient state of
hypogonadotropic hypogonadism associated with prolongation of the childhood
growth phase, delayed skeletal maturation, delayed pubertal growth spurt, and
low IGF-1 secretion. On a GnRH stimulation test, these children will have
prepubertal levels of FSH, LH, estradiol, and testosterone. Eventually, puberty will
spontaneously occur, resulting in the progression of development in these
children. In most cases, the final adult height does not meet the predicted adult
height, and individuals tend to have a disproportionately short trunk.

 Hypergonadotropic hypogonadism is the failure of the gonads to produce sex

hormones. FSH and LH will be elevated due to minimal negative feedback on the
hypothalamic-pituitary-gonadal axis. There can be many causes of gonadal failure,
including genetics and physical trauma. In boys, Noonan syndrome and myotonic
dystrophy have been known to cause gonadal failure. Additionally, there have been
cases of LH beta-receptor mutations reported in boys resulting in a lack of a
gonadal response. Trauma to the testes by testicular torsion or cryptorchidism is
also a cause of gonadal failure in boys. In females, autoimmune ovarian failure is
a possible cause of hypergonadotropic hypogonadism, with the child likely also
exhibiting signs or symptoms of other autoimmune conditions. Interestingly, half
of the girls with galactosemia have been shown to develop ovarian failure, thought
to be due to toxic metabolites.

 Hypopituitarism is a lack of release of hormones from the pituitary gland.

Delayed puberty is not the only sign of hypopituitarism, as endocrine dysfunctions
such as hypothyroidism, delayed bone growth, and adrenal insufficiency may also
be present. Kallman syndrome is a specific disorder falling under hypopituitarism
where neurons in the developing brain fail to migrate, resulting in anosmia, the
absence of a sense of smell, and a lack of GnRH cells in the hypothalamus.

 Chromosomal abnormalities are a cause of delayed puberty shared by both

males and females. In females, Turner syndrome (45 XO) is a common cause of
ovarian failure resulting from a missing or incomplete X chromosome. Along with
ovarian failure, Turner syndrome has many other identifying characteristics,
including but not limited to a webbed neck, short stature or delayed growth,
coarctation of the aorta, and a "shield" chest with widely spaced nipples. Females
 with Turner syndrome will typically present with delayed puberty or primary
amenorrhea secondary to ovarian failure. A common chromosomal disorder in
males with delayed puberty is Klinefelter syndrome (47 XXY), a chromosomal
abnormality resulting from a random genetic error after conception. These
patients typically present with small testes, gynecomastia, tall stature, long legs,
and short arms. Due to low testosterone, adolescents affected by Klinefelter
syndrome will typically undergo delayed or incomplete pubertal development.

 In addition to the above causes of delayed puberty, pubertal delay can also occur
in several illnesses where hypothalamic dysfunction can occur. Examples are
hypothyroidism, cystic fibrosis, sickle cell disease, celiac disease, and diabetes
mellitus.Poor nutrition and long-term glucocorticoid use have also been linked to
delayed puberty.

Contrasexual Development

Contrasexual development occurs when male or female children develop physical features
of the opposite gender. This condition tends to be more common in girls and is commonly
caused by polycystic ovaries and increased responses by the adrenal gland. Girls will have
a male-like distribution of hair and may develop hirsutism. Girls can also develop
clitoromegaly and lose the contour of the breast mass. Possible causes include Cushing
syndrome, acromegaly, exogenous androgens, adrenal tumors, ovarian tumors, and
hyperprolactinemia. Although contrasexual development is less common in boys, the
cause is typically estrogen-secreting tumors when it does occur.

Clinical Significance

Puberty is a highly significant process and a part of all children’s development into
functional adults. During this time, children begin to gain the capacity for reproduction,
which is essential to discuss with children as they progress through puberty. Discussion
of safe sexual practices is an important aspect of well-child visits and is pertinent to
identifying children with unsafe or high-risk sexual encounters. The discussion of sexuality
by pediatricians or other medical caregivers with young teens as they progress into
adulthood provides a chance for them to speak to someone under confidentiality and ask
specific questions to understand better their sexuality as well as what is considered safe
sexual practices.
 REFERENCES

Lazala C, Saenger P. Pubertal gynecomastia. J Pediatr Endocrinol Metab. 2002

May;15(5):553-60.Skorupskaite K, George JT, Anderson RA. The kisspeptin-GnRH
pathway in human reproductive health and disease. Hum Reprod Update. 2014 Jul-
Aug;20(4):485-500. Styne DM. Physiology of puberty. Horm Res. 1994;41 Suppl 2:3-
6. Rosenfield RL, Lipton RB, Drum ML. Thelarche, pubarche, and menarche attainment in
children with normal and elevated body mass index. Pediatrics. 2009 Jan;123(1):84-
8.Tinggaard J, Mieritz MG, Sørensen K, Mouritsen A, Hagen CP, Aksglaede L, Wohlfahrt-
Veje C, Juul A. The physiology and timing of male puberty. Curr Opin Endocrinol Diabetes
Obes. 2012 Jun;19(3):197-203.Ohta H. [Growth spurts of the bone from infancy to
puberty.]. Clin Calcium. 2019;29(1):9-17.Busch AS, Hollis B, Day FR, Sørensen K,
Aksglaede L, Perry JRB, Ong KK, Juul A, Hagen CP. Voice break in boys-temporal relations
with other pubertal milestones and likely causal effects of BMI. Hum Reprod. 2019 Aug
01;34(8):1514-1522.Auchus RJ, Rainey WE. Adrenarche - physiology, biochemistry and
human disease. Clin Endocrinol (Oxf). 2004 Mar;60(3):288-96.Arain M, Haque M, Johal
L, Mathur P, Nel W, Rais A, Sandhu R, Sharma S. Maturation of the adolescent
brain. Neuropsychiatr Dis Treat. 2013;9:449-61.Whitlock KE, Illing N, Brideau NJ, Smith
KM, Twomey S. Development of GnRH cells: Setting the stage for puberty. Mol Cell
Endocrinol. 2006 Jul 25;254-255:39-50Wennink JM, Delemarre-van de Waal HA,
Schoemaker R, Schoemaker H, Schoemaker J. Luteinizing hormone and follicle
stimulating hormone secretion patterns in boys throughout puberty measured using
highly sensitive immunoradiometric assays. Clin Endocrinol (Oxf). 1989 Nov;31(5):551-
64.Klein DA, Emerick JE, Sylvester JE, Vogt KS. Disorders of Puberty: An Approach to
Diagnosis and Management. Am Fam Physician. 2017 Nov 01;96(9):590-599. Blondell
RD, Foster MB, Dave KC. Disorders of puberty. Am Fam Physician. 1999 Jul;60(1):209-
18, 223-4.Chen M, Eugster EA.