Gonad Overview

Andrew J Behnke, MD, FACE

Associate Professor of Internal Medicine
Chief, Endocrinology Section
Virginia Tech College of Medicine
Roanoke, VA USA
Learning Objectives
After review of lecture content, the successful student should be able
to
1. Define menopause, premature menopause, and perimenopause.
2. Compare and contrast normal physiology and hormone levels in the menstruating
years with the physiologic changes and hormone levels that occur as a result of
menopause.
3. Recite changes in the hypothalamic-pituitary-ovarian axis associated with
menopause transition (MT) and menopause.
4. Describe symptoms, signs and physical exam findings seen in women undergoing
MT.
5. Recognize the physiologic changes and mechanisms that occur during hot flushes.
Learning Objectives (cont’d.)
6. Recall that FSH is the most consistent test to confirm presence of menopause.
7. Understand psychosocial impact of MT.
8. Describe the various treatments available for the symptoms of menopause, and
understand the benefits and risks especially in light of the WHI study.
 READINGS
Harrisons Chapter 388: Menopause and Postmenopausal Hormone Therapy

Goldman-Cecil Medicine, 227, 1588-1593.e1

Harrisons Ch 388 (20th Ed)
Review – the Ovary Ovarian Follicles:
Primordial
Primary
Secondary
Graafian (Tertiary)

--> like the testicular Leydig cells,

contain Reinke crystals and
secrete testosterone.
Review: Follicle change over time
Review – Hormone Production
in the Ovary
Types of estrogen

 Estradiol - Primarily produced by theca and granulosa cells of the

ovary; it is the predominant form of estrogen found in
premenopausal women
 Estrone -a product of the peripheral conversion of androstenedione.
It is the predominant form of circulating estrogen after menopause
 Estriol - The estrogen the placenta secretes during pregnancy; in
addition, it is the peripheral metabolite of estradiol and estrone; it is
not secreted by the ovary
Sources of estrogens

 Ovaries have 17 HSD and Aromatase- can

produce estradiol
 Adrenal glands make Androsteindione
 Androsteidione can be converted to estrone
by fat cells
 Steroid Hormone serum concentrations in
women at different stages
Hormone Premenopausal Postmenopausal Post-oophorectomy

Testosterone (ng/dL) 325 (range 200-600) 230 110

Androstenedione (ng/dL) 1,500 (500 – 3000) 800-900 800-900

Estrone (pg/dL) 30-200 25-30 30

Estradiol (pg/dL) 35-500 10-15 15-20

Obstetrics and Gynecology, 7th ed., Beckmann et al. 2014. Table 41.2, page 364
Review
Prolactinoma
Prolactinoma
PCOS
PCOS

 Polycystic ovary syndrome (PCOS) is a heterogeneous disorder in which there is

 (1) oligo-ovulation or anovulation
 (2) hyperandrogenism, or
 (3) polycystic ovaries on ultrasound, and in whom other etiologies have been eliminated.
 PCOS is the classic disorder in which the amenorrhea or oligomenorrhea results from
inappropriate feedback of gonadal steroids from the ovaries
PCOS
PCOS- Pathobiology

 It is a functional derangement, perhaps involving insulin-like growth factors such as IGF-I

within the ovary, results in abnormal gonadotropin secretion.
 PCOS is characterized by insulin resistance and compensatory hyperinsulinemia
 There is increasing evidence of specific genetic abnormalities in some women with PCOS.
Clinical Manifestations

 Patients usually present with amenorrhea, hirsutism, and obesity

 Excess androgen from any source or increased extraglandular conversion of androgens to
estrogens can lead to the typical findings of PCOS.
 Included are such diverse disorders as Cushing syndrome, mild congenital adrenal
hyperplasia, virilizing tumors of adrenal or ovarian origin, hyperthyroidism and
hypothyroidism, obesity, and primary PCOS with no other recognizable cause.
 In the primary syndrome, the irregular menses, mild obesity, and hirsutism begin during
puberty and typically become more severe with time
 LH concentrations tend to be elevated, with relatively low and constant FSH levels.
 Levels of most circulating androgens, especially testosterone, tend to be mildly elevated.
PCOS Treatment
 Weight loss
 Metformin
 Clomiphene ( for ovulation induction)
 Oral Contraceptives
 Spironolactone ( decreased testosterone)
Menopause
Menopause

 Menopause is the loss of ovarian production of estrogen:

 a loss of ovarian sensitivity to gonadotropin stimulation (LH and FSH)
 Decreased # of ovarian follicles
 Result: cessation of estrogen production by the ovaries
 This results in a lack of negative feedback (or decreased feedback
inhibition by estrogen) on the hypothalamus and pituitary glands.
 No estrogen is present to feed back to stop production of GnRH -> LH
and FSH.
 FSH is the best test to assess ovarian failure
 Harrison’s Principles of Internal Medicine, 19 e.,
Menopause and Postmenopausal Hormone Therapy

http://accessmedicine.mhmedical.com/ViewLarge.aspx?figid=98732192&gbosContainerID=0&gbosID=0
 Natural menopause – 12 months of amenorrhea with no
obvious pathologic cause
 Induced menopause – permanent cessation of menstruation
after bilateral oophorectomy or ablation of ovarian function
(chemo, radiation)
 Premature menopause – at or before age 40; can be natural or
induced (1% of women)
 Perimenopause/menopause transition/climacteric – hormonal
and menstrual cycle changes that occur a few years before and 12
months after the final menstrual period resulting from natural
menopause
Menopause
 Age at menopause ranges from 44-55 (95% of women in US
fall in this range); does not vary across ethnicity or race.
 Average age is 51.
 Age of menopause is NOT influenced by age of menarche, # of
ovulations or height.
 It has not changed significantly in the past century.
 On average, cigarette smokers experience menopause
approximately 1-2 years earlier than nonsmokers do.
The Stages of Reproductive Aging Workshop +10 (STRAW +10) staging system for reproductive aging in women. AMH, antimüllerian hormone; FSH,
follicle-stimulating hormone. (From SD Harlow et al: Menopause 14:387, 2012. Reproduced with permission.)

Citation: Menopause and Postmenopausal Hormone Therapy, Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Harrison's
Principles of Internal Medicine, 20e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?
sectionid=192287890&bookid=2129&jumpsectionid=192287895&Resultclick=2 Accessed: March 14, 2020
Copyright © 2020 McGraw-Hill Education. All rights reserved
Physiologic changes
Hypothalamus-Pituitary-Ovarian Axis
Reproductive years
 GnRH is released in pulsatile fashion by arcuate nucleus
of medial basal hypothalamus
 Binding to GnRH receptors on pituitary stimulates cyclic
LH and FSH release
 These hormones stimulate production of ovarian steroids:
estrogen, progesterone, and also inhibin (A and B)
 All provide feedback to pituitary
Early Menopause Transition (MT)
 FSH rises slightly
 Estradiol production fluctuates
 Testosterone levels do not vary much during MT
Late MT
 Impaired folliculogenesis with accelerated rate of
loss of follicles
 FSH and LH rise to levels four times greater;
decreased inhibin
 GnRH is at its greatest amplitude
 Ovarian steroid hormone release eventually ceases
with progression to menopause
Ovary
 1-2 Million oocytes are present at birth.
 By puberty, 400,000 oocytes remain.
 Depletion of follicles accelerates in late 30s and 40s and
continues until menopause
 Ovarian size decreases with resultant difficulty palpating
during bimanual exam
 A – Reproductive Years B - Menopause

http://accessmedicine.mhmedical.com/ViewLarge.aspx?figid=41727426&gbosContainerID=0&gbosID=0
 Menopausal symptoms
Consistently associated Symptoms
 hot flashes
 night sweats
 vaginal dryness, sexual dysfunction
 trouble sleeping

 Secondary sx from age, stress:

 depression, anxiety, labile mood, memory loss, fatigue, headache, joint
pains, weight gain, and urinary incontinence.
 Note that many secondary sx may be from sleep deprivation.
Nonspecific.
Central thermoregulation *
 Vasomotor symptoms (hot flashes/hot flushes, night sweats) can
affect up to 50% (or more) of women going through MT – with
symptoms present on average of 5 years, but may be longer (10 years)
 Added risk factors for developing vasomotor symptoms:
 low exercise level
 smoking
 increasing BMI
 ethnicity
 lower socioeconomic status
 prior premenstrual dysphoric disorder
(H. B. [Ed.] [2016])
Hot Flush

 A hot flush is a sudden feeling of warmth, generally most

intense over the face, neck, and chest.
 The duration is variable, but it averages approximately 4
minutes.
 It is often accompanied by sweating that can be profuse
and followed by a chill.
 Can also happen in men with loss of testosterone
 A hot flush usually lasts 1-5 minutes, with temperature
increases of the digits measuring 1.0-1.5oc higher.
 Upper body (face, neck, chest) may begin to sweat with
sensations of a “heat wave.”
 Accompanied by sweating (profuse) and then a chill
 Both blood pressure and heart rate increase.
 Palpitations, anxiety and irritability may be present.
 Plasma levels of norepinephrine are increased before and
during hot flushes
(Niacin)
Bone loss

 Positive bone balance is maintained from adolescence to age 35, then

bone mass declines
 Estrogen regulates bone resorption
 At menopause, decrease in estrogen results in increased bone
resorption.
 Estrogen inhibits Osteoclast, so loss of estrogen results in increased
osteoclast activity.
 Once in menopause, loss may be 2-5% per year for 5-10 years, then
1% per year thereafter
 Contributes to risk of osteopenia, osteoporosis, and fracture
Weight gain distribution

 Metabolism slows, reducing caloric requirements

 Fat is more likely to be deposited in the abdomen and
viscera
 Increased risk of developing insulin resistance
Cardiovascular

 Framingham data showed that estrogen contributes to greater

HDL levels in premenopausal women
 Loss of estrogen affects risk of CVD such that a 70-year-old
female has a CVD risk identical to that of a male of
comparable age
 Total cholesterol and LDL levels increase as do levels of
fibrinogen, plasminogen activator inhibitor-1, and factor VII.
HDL drops.
Skin

 Hyperpigmentation (lentigo) may occur, especially in sun-

exposed areas
 Lower collagen content leads to wrinkles and loss of elasticity
 More susceptible to abrasion and trauma
 Decreased blood supply may lead to dry skin and itching
 Diminished sebaceous gland secretion may compound skin
dryness
 Reduced SHBG -> more free testosterone -> more facial hair
Reproductive tissue changes

 A significant reduction in volume and tissue density is seen in breast

tissue, with greater adipose tissue present on mammography.
 Estrogen-dependent tissues:
 Vaginal epithelium
 Cervix and endocervix
 Endometrium and myometrium
 Uroepithelium
 With decreasing estrogen production, these tissues become atrophic ->
sx.
 Rugae of the vagina flatten and epithelium thins, leading to
petechial hemorrhage or bleeding with intercourse.

 Vaginal pH becomes more alkaline, with increased risk of bacterial

vaginosis.

 Estrogen deficiency diminishes production of vaginal lubricant, reduces

blood flow, and may lead to anorgasmia, dyspareunia, atrophic vaginitis
(w/itching and burning).

 Urethral shortening from atrophic changes (“atrophic urethritis”) may

result in stress incontinence, and increased incidence of UTI.
 Serum gonadotropin and estrogen
 Estrogen levels may be normal, elevated or low
depending on the stage of MT – only at menopause are
levels extremely low or undetectable
 An FSH level equal or greater than 25 IU/L can be used
to document ovarian failure/menopause
Treatment
Estrogen Replacement

 Conjugated estrogen (Premarin) 0.3,0.625, 1.2 mg

 Plant derived- (Ogen) 1 mg, 2 ms

 Estrogen and Progesterone

 Prempro
Estrogen therapy
 17-beta Estradiol is oxidized in the enterohepatic circulation to E1 (estrone).
 17-beta Estradiol remains unaltered when administered by any other route –
transvaginal, transdermal, transbuccally, IV or IM.
 Transvaginally it is poorly controlled but remains at low levels when used
appropriately.
 Transdermally it is sustained and stable – may be preferable in many.
 Combined estrogen with progestin therapy – if intact uterus. Cyclic vs
continuous. Oral vs transdermal.
 Medroxyprogesterone -> many SEs (affective and wt gain)
 Norethindrone acetate or norethynodrel – in more recent preparations.
FY
I
Hormone Replacement: over the years

 Women’s Health Initiative

 Large, multicenter, randomized clinical trial
 17,000 patients
 Amended thinking – mid 2010’s ->
 Only use HRT for short-term relief of menopausal sx.
HRT ERT
Benefits and risks of the two hormone therapy formulations evaluated in the Women’s Health Initiative, in women aged 50–59 years. Results are shown for
the two formulations, conjugated equine estrogens (CEE) alone or in combination with medroxyprogesterone acetate (MPA). Risks and benefits are
expressed as the difference in number of events (number in the HT group minus the number in the placebo group) per 1000 women over 5 years. (Data
are from JE Manson et al: JAMA 310:1353, 2013.) (Graphic display is from JE Manson, AM Kaunitz: N Engl J Med 374:803, 2016 and is reproduced with
permission.)

Citation: Menopause and Postmenopausal Hormone Therapy, Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Harrison's
Principles of Internal Medicine, 20e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?
sectionid=192287890&bookid=2129&jumpsectionid=192287895&Resultclick=2 Accessed: March 14, 2020
Copyright © 2020 McGraw-Hill Education. All rights reserved
 HRT and Risk-Benefit Analysis
 Risk of breast cancer is increased 26% in women receiving HRT but not ERT
 Risk of DVT and PE is doubled in women on HRT.
 Risk of stroke is increased by 41% in women on HRT and ERT
 Hepatic estrogen receptor agonist activity upregulates protein synthesis, including
clotting factors.
 Risk of MI is increased by 29% in women on HRT BUT NOT ERT!!!
 In spite of beneficial effects on lipid panel.
 HRT does have a beneficial effect on bone density.
 Main indication for use of HRT in perimenopause and menopause is to control the
vasomotor symptoms, if they are severe enough to merit the risks as well.

http://accessmedicine.mhmedical.com.ezproxy.liberty.edu/ViewLarge.aspx?figid=98732205&gbosContainerID=0&gbosid=0
Contraindications to Hormone replacement
therapy
 Undiagnosed abnormal genital bleeding
 Known or suspected estrogen-dependent neoplasia
 Active DVT, PE or a history of these
 Active or recent arterial thromboembolic disease (CVA, AMI)
 Liver dysfunction or disease
 Known or suspected pregnancy
 Hypersensitivity to hormone therapy preparations
1. Behavioral and Alternative Therapies
• Holistic approach
2. Vaginal treatments alone
3. Medical Therapies
• Hormone replacement
• Estradiol, Estrone, Estriol
• Progestins (but increased SEs)
• Other RX drugs
• SSRIs (esp paroxetine)
• SNRIs (esp venlafaxine)
• Cetirizine
• Clonidine (maybe…)
• Gabapentin (in trials…)
SUMMARY

 Menopause is defined as loss of ovarian production of estradiol resulting from decreased

sensitivity to FSH.
 It occurs around the age of 50 and is preceded by a pre- and peri- menopause time
highlighted by mensural irregularities and hormone changes.
 Common symptoms are vasomotor hot flashes, amenorrhea, depression and sleep
disturbances.
 Hot flashes are mediated by neural dysregulation. They can last for years and can be
treated by estrogen replacement and SSRI.
 HRT can decrease hot flashes and bone loss, but long term use increased the risk of Stroke
and Breast cancer ( ERT increase in Stroke)
Male Gonadal Disorders
Andrew J Behnke, MD
 Text References
• Required
• Goldman-Cecil Medicine, 221, 1537-1547.e2
• Harrisons Ch. 384 ( 20th Ed)
• Recommended
• Greenspans’ Basic and Clinical Endocrinology, 9th Ed. Ch 12 (395-423)
• First aid for USMLE. 622-625
 Learning Objectives
• Review normal testosterone physiology and action (4-17)
• Understand the definition and causes of hypogonadism (18-21)
• Acquire the ability to diagnose hypogonadism and assess the need for
treatment (22-24)
• List the causes of primary hypogonadism especially Klienfleters
Syndrome (25-28)
• Identify secondary causes of hypogonadism including prolactinoma and
disorders of the hypothalamic pituitary axis (29-32)
• Describe the effects of alcohol and drugs on testosterone (33-35)
• List the available treatments for hypogonadism (36-37)
 Male Reproductive System
• (1) Extra-hypothalamic central nervous system (CNS)
• (2) Hypothalamus
• (3) Pituitary
• (4) Testes
• (5) Sex steroid–sensitive end organs
• (6) Sites of androgen transport and metabolism
Male Reproductive System
 Testosterone
• Testosterone is the principal male hormone secreted by the testes; approximately 5
to 10 mg/day is produced in adult men.
• Testosterone circulates mainly bound to two plasma proteins: sex hormone–binding
globulin (SHBG) and albumin.
• SHBG is produced in the liver.
• In young adult men, approximately 54% of testosterone is bound to albumin, 44%
is bound to SHBG, and 2 to 3% is unbound.
Testosterone Synthesis
Testosterone Metabolism
Androgen metabolism and actions. SHBG, sex hormone–binding globulin.

Citation: Disorders of the Testes and Male Reproductive System, Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Harrison's
Principles of Internal Medicine, 20e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?
bookid=2129&sectionid=192287591 Accessed: March 29, 2020
Copyright © 2020 McGraw-Hill Education. All rights reserved
 SHBG
• SHBG levels are increased in hyperestrogenic states, hyperthyroidism, aging,
phenytoin treatment, anorexia nervosa, and prolonged stress.
• SHBG levels are lowered in hyperandrogenic states. Obesity, diabetes,acromegaly,
and hypothyroidism.
• In conditions with abnormal SHBG levels the total testosterone measurement may
be misleading. Measurement of non–SHBG-bound testosterone may allow better
interpretation of the active testosterone levels.
Testicular Feminzation
• XY Karyotype ( Normal Male).
• Male levels of testosterone.
• Phenotypically female.
• Amenorrhea.
• 5 alpha reductase deficiency.
• Do have testes.
Testosterone effects
For Men Only???
Testosterone Effects on Erection
 Testosterone and aging/obesity
• Free serum testosterone levels progressively
decrease with aging .
• Total testosterone decreases with obesity, but not
free testosterone.
Hypogonadism Symptoms
Hypogonadism Signs
• Normal testicular size ranges from 3.6
to 5.5 cm in length, 2.1 to 3.2 cm in
width, and 15 to 35 mL in volume.
Tanner Stages
 Labs
• Morning serum total testosterone level x2 . If repeatedly
below 230 ng/dL (8 nmol/L), probably hypogonadal.
• If between 230 and 350 ng/dL ( borderline) and LH is not
increased, check a free testosterone.
• A serum total testosterone level above 350 ng/dL (12 nmol/l)
indicates that hypogonadism is very unlikely.
• LH and FSH levels (distinguish primary from secondary
hypogonadism)
• Semen analysis is the “cornerstone” of the laboratory
examination for male infertility.
Evaluation of hypogonadism. GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; T, testosterone.

Citation: Disorders of the Testes and Male Reproductive System, Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Harrison's
Principles of Internal Medicine, 20e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?
bookid=2129&sectionid=192287591 Accessed: March 29, 2020
Copyright © 2020 McGraw-Hill Education. All rights reserved
 Hypogonadism
• Primary hypogonadism indicates that the
abnormality originates in the testis; it is
characterized by increased serum LH and FSH
levels.
• Secondary hypogonadism indicates a defect at
the hypothalamus or pituitary, resulting in
decreased gonadotropins (LH, FSH, or both).
 Primary Hypogonadism

• Low testosterone.
• High gonadotrophins ( LH and FSH).
• Examples: Kleinfelters Syndrome (XXY)
 Klinefleters Syndrome
• Normal development of the penis and scrotum
• Testes are small and firm.
• Gynecomastia is frequent.
• Signs of testosterone deficiency occur in most affected
adults, and most have azoospermia.
• The usual karyotype is 47,XXY.
• A common disorder that occurs in 1 in 500 to 1000 men
Kleinfelters Syndrome
 Primary Hypogonadsim
•Congenital disorders
•Chromosome disorders
•Klinefelter and related syndromes (e.g., XXY, XXY/XY, XYY, XX males)
•Testosterone biosynthetic enzyme defects
•Myotonic dystrophy
•Developmental disorders
•Prenatal diethylstilbestrol syndrome
•Cryptorchidism
•Acquired defects
•Orchitis
•Mumps and other viruses
•Granulomatous disease (e.g., tuberculosis, leprosy)
•Human immunodeficiency virus infection
•Infiltrative disease (e.g., hemochromatosis, amyloidosis)
•Surgical, traumatic injuries, torsion of testis
•Irradiation
Primary Hypogonadism, Continued.
•Toxins (e.g., alcohol, fungicides, insecticides, heavy metals, cottonseed oil, DDT, other environmental
“endocrine disruptors”)
•Drugs
•Cytotoxic agents
•Inhibitors of testosterone synthesis and antiandrogens (e.g., ketoconazole, cimetidine, flutamide, cyproterone,
spironolactone)
•Ethanol, opioids, other recreational drugs
•Autoimmune testicular failure
•Isolated
•Associated with other organ-specific disorders (e.g., Addison disease, Hashimoto thyroiditis, insulin-
dependent diabetes)

•Systemic diseases * (e.g., cirrhosis, chronic renal failure, sickle cell disease, acquired immunodeficiency
syndrome, amyloidosis)
•Aging *
 Secondary Hypogonadism
• Caused by a decrease of gonadotropins
• Low testosterone, Low FSH/LH
 Prolactinoma
• Tumors are usually large (>1 cm in diameter;
macroadenomas).
• Usually present with hypogonadism, erectile dysfunction, and
visual manifestations from suprasellar extension.
• In small tumors, hypogonadotropic hypogonadism may be due
to suppressive effects on GnRH
• In large tumors, it also may be due to a mass effect damaging
the non-neoplastic gonadotrophs.
 Secondary Hypogonadism
IDIOPATHIC OR CONGENITAL
•Isolated deficiency of gonadotropin-releasing hormone
•With anosmia (Kallmann syndrome)
•With other abnormalities (Prader-Willi syndrome, Laurence-Moon-Biedl syndrome,
basal encephalocele)
•Partial deficiency of gonadotropin-releasing hormone (fertile eunuch syndrome)
•Multiple hypothalamic and pituitary hormone deficiency
•Pituitary hypoplasia or aplasia
Secondary Hypogonadism- Continued
ACQUIRED
•Traumatic brain injury, after surgery or irradiation
•Neoplastic
•Pituitary adenoma (prolactinoma, other functional and nonfunctional tumors)
•Craniopharyngioma, germinoma, glioma, leukemia, lymphoma
•Pituitary infarction, carotid aneurysm
•Infiltrative and infectious diseases of hypothalamus and pituitary (sarcoidosis, tuberculosis, coccidioidomycosis,
histoplasmosis, syphilis, abscess, histiocytosis X, hemochromatosis)
•Autoimmune hypophysitis
•Aging and systemic diseases *
•Obesity
•Malnutrition
•Anorexia nervosa, starvation, renal failure, liver failure
Obesity
 Central Hypogonadism Drug effects
• Antiandrogens
• Estrogens and antiestrogens
• Progestogens
• Glucocorticoids
• Cimetidine
• Spironolactone
• Digoxin
• Drug-induced hyperprolactinemia (metoclopramide, tranquilizers,
antihypertensives)
 Drugs of Abuse
• Lower testosterone, mainly by decreasing LH.
• Marijuana
• Heroin
• Methadone
• Medroxyprogesterone acetate, other progestins, and estrogens.
• Lower testosterone, mainly by decreasing LH.
• Raise Testosterone
• Testosterone analogs
• Clomid
• Aromatase Inhibitors
.
 Ethanol
Ethanol, independent of its role in causing liver
disease, inhibits testosterone biosynthesis.

Estradiol levels are usually elevated. This results in

an increased ratio of serum estradiol to testosterone,
often associated with gynecomastia.
ROUTE
Treatment
PREPARATION DOSE AND FREQUENCY OF
ADMINISTRATION
Oral * Testosterone undecanoate 158 to 396 mg PO two or three
times daily with food
Buccal Transbuccal testosterone, 30 mg two times daily
mucoadhesive tablets

Injection Testosterone enanthate and 100 mg/wk IM or 150-200 mg

cypionate IM every 2 wk
50 to 100 mg/week SC
Testosterone undecanoate 750-1000 mg IM every 10-12 wk
Implant Testosterone implants 75-mg pellets (in United States),
6-10 inserted under the skin
every 4-6 months
Transdermal Nonscrotal patch Two patches, each delivering
Androderm testosterone 2.5 mg/day; or one
patch delivering testosterone
5 mg/day
Testoderm TTS One patch delivering testosterone
5 mg/day
Transdermal gels AndroGel or Testogel; Testim; 1 to 2% gel applied once daily
Axiron; Fortesta delivering 50-100 mg
testosterone on skin and 5 to
10 mg to body
 Testosterone Treatments
BENEFITS
•Development or maintenance of secondary sex characteristics
•Improved libido and sexual function
•Increased muscle mass and strength
•Increased bone mineral density
•Improves anemia
•Decreased body and visceral fat
•Improved mood
•Effect on cognition (?)
•Effect on vitality and quality of life (?)
•Decreased cardiovascular disease risk (epidemiologic studies); clinical study
no benefits/risk
 RISKS
• Fluid retention
• Gynecomastia
• Acne, oily skin
• Increased hematocrit, erythrocytosis
• Decreased high-density lipoprotein cholesterol (oral agents produce more effect)
• Sleep apnea
• Decreased Sperm Count
• Aggressive behavior (?)
• Prostate disease
• Benign prostatic hyperplasia (?)
• Carcinoma of prostate (aggravate existing cancer)
• Increased cardiovascular adverse events in one study in frail elderly men
with multiple comorbid conditions
 Summary
• Testosterone promotes development of secondary sex characteristics, muscle
strength, bone development and red blood count.
• Testosterone is bound to proteins ( SHBG).
• The testis produces both testosterone (Ledig) and sperm cells (Sertoli)
• Erection and libido are different in pathophysiology.
• Primary hypogonadism is characterized by a low testosterone and high
gonadotrophins (Kleinfelters Syndrome).
• Secondary hypogonadism is characterized by low testosterone and non elevated
gonadotrophins (Prolactinoma, drug effects).
• Testosterone treatment needs to be closely monitored to avoid adverse effects.