SEX HORMONES

MALE reproductive organs

The TESTIS is responsible for producing Testosterone(about 7mg/day from Leydig cells) and mature sperm from seminiferous tubules. Testosterone is usually bound to a protein, either albumin or sex hormone binding globulin (SHBG) in the blood and only about 1%-3% of testosterone in the blood is free.

• Deficiency is testosterone can occur in two different ways
• Primary Hypogonadism
• Usually associated with gynecomastia which results from elevated FSH/LH stimulating testicular aromatase, thereby converting more testosterone to estradiol
• Causes
• Developmental defects: Klinefelter’s Syndrome 46, XXY
• Acquired: Mumps, Radiation, Drugs (ketaconazole, spironolactone, cyproterone, phenytoin, cabamazepine, ethanol, cyclophosphamide, etc), systemic illness (renal failure, liver failure, sickle cell disease, chronic illness, hyperthyroidism, HIV, immune disorders), or traumatic.
• Secondary Hypogonadism – problem at pituitary or hypothalamus
• Causes
• Congenital (Idiopathic hypogonadotropic hypogonadism, Kallmann’s syndrome, Androgen receptor dysfunction), Pituitary tumor, elevated prolactin, infiltrative disorders (histiocytosis, hemochromocytosis, sarcoidosis), traumatic, CNS infection, critical illness, chronic narcotic use, exogenous steroids, brain irradiation, pituitary apoplexy, malnutrition, obesity, sleep apnea, diabetes,
• Symptoms include
• Fatigue, loss of muscular strength, poor libido (sex drive), hot flushes, sexual dysfunction.
• Treatment
• Clomiphene
• hCG
• Testosterone replacement (injectable, gel, patch or buccal/oral)
• Excess Testosterone
• Male Anabolic steroid abuse
• Seen in Muscle Dysmorphia and Reverse Anorexia Nervosa
• Symptoms include
• Infertility, irritability, tangential or evasive speech, muscular hypertrophy, testicular atrophy, gynecomastia (if abusing testosterone), pustular acne – particularly on the back
• Treatment
• Slowly wean off supplemental testosterone to prevent androgen withdrawal (depression, lassitude, emotional lability, hot flushes)
• Tamoxifen and aromatase inhibitor for gynecomastia
• Tretinoin for acne
• Male Infertility
• Normal semen analysis shows :
• >2mL volume, pH 8-9, +fructose, Sperm count 2-10million/mL, >50% motility and >14% normal forms
• Treatment (in secondary hypogonadism)
• Injectable gonadotropins or pulsatile GnRH
• Human Chorionic Gonadotropin (HCG) (lower cost and longer duration of action)
• Recombinant FSH is added to HCG if hypogonadism severe or failed spontaneous puberty.

Gynecomastia

Glandular enlargement of the male breast that is usually asymmetric, one sided and may be tender.

• Due to excessive estrogen action or increased estrogen-androgen ratio
• Causes due to
• Puberty, aging
• Decreased production or action of androgen
• Increased estrogen production
• Systemic illness (liver, kidney, thyroid problems; malnutrition or refeeding)
• Drugs
• Idiopathic
• Treatment
• Identify underlying problem
• Surgery for cosmetic reasons
• Androgens, anti estrogens and aromatase inhibitor to reduce symptoms

FEMALE reproductive organs

The OVARIES under the stimulation of LH produce androstenedione and testosterone from androgen-producing theca cells. Under stimulation of FSH, the ovarian granulosa cells stimulate expression of aromatase which converts androstenedione and testosterone to estradiol and triggers ovulation. The granulosa cells undergo a process called luteinization after ovulation (release of egg), forming a corpus luteum that produces progesterone. Progesterone withdrawal follows two weeks later and leads to menstrual bleeding unless fertilization occurs.

Absent menses

• Primary Amenorrhea
• No spontaneous menses by age 16 (or by age 14 – if no secondary sexual characteristics
• Secondary Amenorrhea (or Hypothalamic Amenorrhea)
• Absence of menses for 3 consecutive months in a female who previously had menses.
• Oligomenorrhea (irregular or infrequent menses)
• Causes
• Rule out pregnancy
• Anatomic defect (Mullerian duct agenesis, androgen insensitivity syndrome, transverse vaginal septum / imperforate hymen, enzyme deficiency; Asherman’s syndrome with endometrial scarring)
• Ovarian Failure or Premature Ovarian failure (Turner syndrome; autoimmune oophritis)
• FSH > 35mU/mL
• Chronic anovulation with normal estrogen level
• PCOS, hyperprolactinemia, Cushing’s syndrome, mild 21-hydroxylase deficiency…all of which you see excess of androgen
• Chronic anovulation with low estrogen level
• Hypothalamic amenorrhea, Hypogonadotropic hypogonadism, Kallmann’s
• Recent Oral Contraceptive Use (Birth Control Pills)
• Hypothalamic Amenorrhea can be caused by
• Tumor or infiltrative lesion (like lymphoma or sarcoidosis)
• Functional causes (like stress or excessive exercise)
• Effects of radiation or chemotherapy

Polycystic Ovary Syndrome

This is a common cause of infertility in young women of reproductive age.

• Features include
• Menstrual irregularities associated with chronic oligomenorrhea or anovulation
• Need to evaluate prolactin (milk production = galactorrhea) and thyroid (TSH) function
• Symptoms of hyperandrogenism
• Hirsutism or excessive hair growth (terminal hairs on chin, upper lip, nipples and lower abdomen); acne, seborrhea, male pattern baldness (androgenic alopecia), virilization (voice deepening and clitoral enlargement)
• Need to rule out other causes:
• Androgen producing tumors (adrenals or ovarian), Cushing’s syndrome (easy bruising, muscle aches) and occult 21 hydroxylase deficiency.
• Polycystic ovaries on pelvic ultrasound
• Insulin resistance and obesity
• LH/FSH >2
• Treatment variable and as follows
• Weight loss, OCP, metformin, topical treatments, spironolactone, clomiphene citrate

Hirsutism

Development of (androgen dependent) terminal body hair (in women) that would not normally be seen : face, chest, back and abdomen

• Due to increased androgen production by ovaries, adrenal glands or increased target-end organ production of androgen
• Common causes:
• PCOS, idiopathic, adrenal hyperplasia/neoplasm, ovarian neoplasm, drugs (OCP, diazoxide, androgen, phenytoin, cyclosporine, minoxidil), Cushing’s, Acromegaly, Hyperprolactinemia, Obesity, Pregnancy related hyperandrogenism
• Treatment

Topical treatment, OCP, antiandrogens, glucocorticoids (CAH)