Female Reproductive Disorders and Breast Disorders

Chapter 21 Female Reproductive Disorders and Breast Disorders

I. Sexually Transmitted Diseases and Other Genital Infections

• Summary of infections (Table 21-1 and Fig. 21-1)

II. Vulva Disorders

A. Bartholin gland abscess

• Most often caused by Neisseria gonorrhoeae

B. Non-neoplastic dermatoses

1. Lichen sclerosis (Fig. 21-2)

a. Usually occurs in postmenopausal women

b. Thinning of the epidermis

Table 21-1 Sexually Transmitted Diseases and Other Genital Infections

21-1: Genital infections. A, Candida. Bottom arrow shows elongated yeasts (pseudohyphae), top arrow shows yeasts. B, Gardnerella vaginalis. Superficial squamous cells are covered by granular material representing bacterial organisms attached to the surface. C, Herpes type 2. Arrows show ulcerated, red lesions on the shaft of the penis. D, Herpes type 2. Biopsy showing a multinucleated squamous cell with smudged, “ground glass” nuclei with intranuclear inclusions (arrow). E, Human papillomavirus. Numerous keratotic papillary processes are present on the surface of the labia. These are called venereal warts or condylomata acuminata. F, Neisseria gonorrhoeae. Neutrophils (arrow) show numerous, phagocytosed gram-negative diplococci. 21-1 cont’d: G, Treponema pallidum. Note the well-demarcated primary chancre just distal to the glans penis. H, Treponema pallidum. Note the characteristic palmar papules and plaques of secondary syphilis. I, Treponema pallidum. Note the flat, plaque-like lesions (arrows) of condyloma latum. J, Trichomonas vaginalis. Note the numerous pear-shaped, flagellated organisms (arrows).

(A and D from Atkinson BF: Atlas of Diagnostic Cytopathology. Philadelphia, WB Saunders, 1992, pp 76, 78, and 80, Figs. 2–49B, 2–55, and 2–63, respectively; B and E from Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, pp 261 and 260, Figs. 13–10B and 13–8, respectively; C from Bouloux P-M: Self-Assessment Picture Tests: Medicine, Vol 1. St. Louis, Mosby, 1996, p 17, Fig. 33; F from Greer I, Cameron IT, Kitchener HC, Prentice A: Mosby’s Color Atlas and Text of Obstetrics and Gynecology. St. Louis, Mosby, 2000, p 274, Fig. 10–50; G from Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 537, Fig. 18–13; H from Lookingbill D, Marks J: Principles of Dermatology, 3rd ed. Philadelphia, WB Saunders, 2000, p 124, Fig. 10-17; I from Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 553, Fig. 18-13; J from Kumar V, Fausto N, Abbas A: Robbins and Cotran’s Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 1064, Fig. 22-4.)

21-2: Lichen sclerosis. The vulva shows a parchment-like appearance (arrow).

(From Savin JAA, Hunter JAA, Hepburn NC: Diagnosis in Color: Skin Signs in Clinical Medicine. London, Mosby-Wolfe, 1997, p 124, Fig. 4.81.)

Lichen sclerosis: thin epidermis; parchment-like skin

• Parchment-like appearance of skin

c. Small risk for developing squamous cell carcinoma

2. Lichen simplex chronicus

a. White plaque-like lesion (leukoplakia)

Lichen simplex: leukoplakia (hyperplasia)

• Due to squamous cell hyperplasia

b. Small risk for developing squamous cell carcinoma

C. Benign and malignant tumors

1. Papillary hidradenoma

Papillary hidradenoma: painful apocrine gland tumor

a. Benign tumor of the apocrine sweat gland

b. Painful nodule on the labia majora

2. Vulvar intraepithelial neoplasia (VIN)

a. Dysplasia ranges from mild to carcinoma in situ

b. Strong human papillomavirus (HPV) type 16 association

VIN: HPV 16 association

c. Precursor for developing squamous cell carcinoma

3. Squamous cell carcinoma

a. Most common cancer

b. Risk factors

(1) HPV type 16

(2) Smoking cigarettes

(3) Immunodeficiency (e.g., AIDS)

c. Metastasize first to the inguinal nodes

4. Extramammary Paget’s disease

a. Red, crusted vulvar lesion

b. Intraepithelial adenocarcinoma

Extramammary Paget’s disease: intraepithelial adenocarcinoma; PAS positive

(1) Tumor derives from primitive epithelial progenitor cells.

(2) Malignant Paget’s cells contain mucin (Fig. 21-3).

• Mucin is periodic acid–Schiff (PAS) positive.

(3) Spreads along the epithelium

• Rarely invades the dermis

5. Malignant melanoma

a. Melanoma cells are histologically similar to Paget’s cells.

21-3: Extramammary Paget’s disease. Large, pink-staining, malignant Paget’s cells (arrows) are disposed singly and in clusters within the epidermis.

(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 1492, Fig. 19-17B.)

Melanoma: PAS negative

b. Unlike Paget’s cells, melanoma cells are PAS negative.

III. Vagina Disorders

A. Rokitansky-Kuster-Hauser (RKH) syndrome

1. Absence of the upper vagina and uterus

RKH syndrome: absence of upper vagina/uterus

2. Anatomic cause of primary amenorrhea

B. Gartner’s duct cyst

1. Remnant of the wolffian (mesonephric) duct

Gartner’s cyst: wolffian duct remnant

2. Presents as a cyst on the lateral wall of the vagina

C. Benign and malignant tumors

a. Benign tumor of skeletal muscle

b. Other locations are the tongue and heart.

2. Embryonal rhabdomyosarcoma

a. Occurs in girls < 5 years old

Embryonal rhabdomyosarcoma: grape-like mass protruding from vagina

b. Necrotic, grape-like mass protrudes from the vagina (Fig. 21-4).

3. Clear cell adenocarcinoma of the vagina (Fig. 21-5)

a. Epidemiology

(1) Occurs in women with intrauterine exposure to diethylstilbestrol (DES)

• DES was used to prevent a threatened abortion.

(3) Vaginal adenosis

(a) Remnants of müllerian glands

• Produces red, superficial ulcerations in the upper portion of the vagina

Vaginal adenosis: red, superficial ulcerations

(b) Precursor lesion for clear cell adenocarcinoma

Clear cell adenocarcinoma of vagina/cervix: associated with DES exposure; adenosis precursor lesion

(4) Small risk for developing the cancer (1:1000)

(5) Cancer may involve upper vagina or cervix.

b. Other DES abnormalities

(1) Abnormally shaped uterus that thwarts implantation

(2) Cervical incompetence

• Common cause of recurrent abortions

4. Vaginal squamous cell carcinoma

Other DES abnormalities: incompetent cervix; abnormal uterine shape

a. Primary squamous cell carcinoma has an HPV type 16 association.

b. Most cancers are an extension of a cervical squamous cancer into the vagina.

IV. Cervix Disorders

A. Clinical anatomy and histology

1. Cervix includes the endocervix + exocervix

• The exocervix begins at the cervical os.

2. Exocervix is normally lined by squamous epithelium.

3. Endocervical glands are normally lined by mucus-secreting columnar cells.

4. Endocervical epithelium normally migrates down to the exocervix.

a. Exposure to the acid pH of the vagina produces squamous metaplasia.

b. The area undergoing metaplasia is called the transformation zone.

(1) This zone is where squamous dysplasia and cancer develop.

Transformation zone: site where squamous dysplasia and cancer develop

(2) It must be sampled when performing a cervical Papanicolaou (Pap) smear.

c. Metaplastic squamous cells block endocervical gland orifices.

(1) Obstruction of outflow of mucus produces nabothian cysts (see Fig. 21-17).

(2) Nabothian cysts are a normal finding in adult women.

B. Acute and chronic cervicitis

1. Epidemiology

a. Accounts for 20% to 25% of patients presenting with vaginal discharge

b. Can be found in any sexually active woman

c. Subdivided into acute and chronic cervicitis

2. Acute cervicitis

a. Acute inflammation is normally present in the transformation zone.

b. Pathologic acute cervicitis; causative agents:

• Chlamydia trachomatis, N. gonorrhoeae, Trichomonas vaginalis, Candida, herpes simplex virus (HSV-2), HPV

c. Clinical findings

(1) Vaginal discharge (most common)

Acute cervicitis: vaginal discharge most common complaint

(2) Pelvic pain

(3) Dyspareunia

(4) Painful on palpation

(5) Bleeds easily when obtaining cultures

(6) Cervical os is erythematous and may be covered by an exudate.

(1) DNA probe for Chlamydia and Neisseria gonorrhoeae

• These organisms account for >50% of acute cervicitis.

Acute cervicitis: C. trachomatis and N. gonorrhoeae > 50% of cases

(2) Wet mount for Trichomonas

(3) Obtain a cervical Pap smear

(1) If culture or DNA probe positive, treat with appropriate antibiotic.

(2) If culture negative, cryosurgery is an option.

(3) Advise safe sex with the use of condoms

3. Chronic cervicitis

• Occurs when acute cervicitis persists

4. Follicular cervicitis

Follicular cervicitis: caused by C. trachomatis

a. Caused by C. trachomatis

b. Pronounced lymphoid infiltrate with germinal centers

c. Chlamydia infects metaplastic squamous cells.

(1) Cells contain vacuoles with red inclusions (reticulate bodies).

Reticulate bodies: produce elementary bodies, the infective particle of Chlamydia

(2) Reticulate bodies develop into elementary bodies, which are infective particles.

d. Cervicitis is the primary source for conjunctivitis and pneumonia in newborns.

C. Cervical Pap smear

a. Screening test to rule out squamous dysplasia and cancer

b. To evaluate the hormone status of the patient

Cervical Pap smear: screen for dysplasia/cancer, evaluates hormonal status

2. Sample sites

• Vagina, exocervix, transformation zone

Because the transformation zone is the site for squamous dysplasia and squamous cancer, it must be adequately sampled. The presence of metaplastic squamous cells or mucus-secreting columnar cells indicates proper sampling. Absence of these cells means that the Pap smear must be repeated.

3. Interpretation of the Pap smear

a. Superficial squamous cells indicate adequate estrogen.

Superficial squamous cells: adequate estrogen

b. Intermediate squamous cells indicate adequate progesterone.

c. Parabasal cells indicate a lack of estrogen and progesterone.

Intermediate squamous cells: adequate progesterone

d. Normal nonpregnant adult woman

Parabasal cells: lack of estrogen and progesterone

• 70% superficial squamous cells, 30% intermediate squamous cells

e. Pregnant woman

• 100% intermediate squamous cells from progesterone effect

f. Elderly woman with lack of estrogen and progesterone

• Atrophic smear with parabasal cells and inflammation

g. Woman with continuous exposure to estrogen without progesterone

• 100% superficial squamous cells

2. Pathogenesis

a. Essentially unknown

b. Inflammation, trauma, pregnancy have been implicated.

3. Clinical findings

Cervical polyp: postcoital bleeding; vaginal discharge

a. Postcoital bleeding

b. Vaginal discharge

4. Treatment is surgical excision.

E. Cervical intraepithelial neoplasia (CIN)

1. Epidemiology

b. Peak incidence is 35 years of age.

c. False negative rate on detecting dysplasia on a cervical Pap smear is ∼︀40%.

d. Risk factors

(1) Early age of onset of sexual intercourse

(2) Multiple, high-risk partners

(3) High-risk types of HPV in a biopsy

(4) Smoking, oral contraceptive pills (OCPs)

(5) Immunodeficiency

2. Classification of CIN

Cervical dysplasia: precursor for squamous cancer

• Mild dysplasia involving the lower third of the epithelium

• Moderate dysplasia involving the lower two thirds of the epithelium

c. CIN III (see Fig. 1-17)

• Severe dysplasia to carcinoma in situ (CIS) involving the full thickness of the epithelium

3. Progression from CIN I to CIN III is not inevitable.

a. Reversal to normal is more likely in CIN I.

b. Requires ∼︀10 years to progress from CIN I to CIN III

c. Requires ∼︀10 years to progress from CIN III to invasive cancer

• Average age for cervical cancer is ∼︀45 years old.

4. Clinical findings

a. Dysplasia is not usually visible to naked eye; colposcopy is required.

• Occasionally, flat to warty appearing condyloma acuminata are visible.

b. Colposcopy findings, after application of acetic acid:

• Acetowhite areas with punctation, mosaic pattern, or abnormal vascularity

• Electrocoagulation, cryotherapy, laser ablation, local surgery (conization)

F. Cervical cancer

1. Epidemiology

a. Least common gynecologic cancer

Cervical cancer: least common gynecologic cancer; importance of Pap smear

• Due to early detection of CIN with Pap smears

b. Higher incidence in developing countries

c. In U.S. population incidence in descending order:

• Hispanic, black, white

d. Majority are squamous cell carcinoma (75–80% of cases).

• Small cell cancer and adenocarcinoma are less common types.

e. Cause and risk factors

• Same as those listed for CIN

2. Clinical findings (Figs. 21-7 and 21-8)

a. Abnormal vaginal bleeding (most common)

• Usually postcoital

21-7: Squamous cell carcinoma of the cervix. Note the bleeding and ulceration in the cervical os.

(Courtesy of Dr. Hector Rodriguez-Martinez, Mexico City.)

21-8: Squamous cell carcinoma of cervix with extension down into the vagina, wall of the urinary bladder (solid arrow) and wall of the rectum (interrupted arrow).

(Courtesy of Dr. Hector Rodriguez-Martinez, Mexico City.)

Cervical cancer: abnormal vaginal bleeding most common sign

b. Malodorous discharge

c. Postcoital bleeding

3. Cancer characteristics

a. Extends down into the vagina

b. Extends out into the lateral wall of the cervix and vagina

c. Infiltrates the bladder wall and obstructs the ureters

• Postrenal azotemia leading to renal failure is a common cause of death.

Cervical cancer: renal failure is a common cause of death.

d. Distant metastases (e.g., lungs)

4. Treatment of invasive cancer

a. Surgery, radiation, or both

b. Chemotherapy in selected cases

• The 1- and 5-year relative survival rates are 88% and 72%, respectively.

V. Reproductive Physiology and Selected Hormone Disorders

A. Sequence to menarche

1. Breast budding (thelarche)

2. Growth spurt

4. Axillary hair

Sequence to menarche: breast budding, growth spurt, pubic hair, axillary hair, menarche

a. Mean age of 12.8 years

b. Anovulatory cycles for 1–1.5 years

B. Summary of the normal menstrual cycle

• Synthesis of sex hormones in the ovary (Fig. 21-9)

1. Proliferative (follicular) phase (Fig. 21-10)

a. Estrogen-mediated proliferation of glands

• Most variable phase of the cycle

21-9: Synthesis of sex hormones in the ovaries. Luteinizing hormone is responsible for stimulation of hormone synthesis in the theca interna surrounding the developing follicle. Follicle-stimulating hormone increases the synthesis of aromatase in granulosa cells. Aromatase converts testosterone to estradiol.

(From Goljan EF: Star Series: Pathology. Philadelphia, WB Saunders, 1998, Fig. 18-1.)

21-10: Menstrual cycle. See text for discussion. FSH, follicle-stimulating hormone; LH, luteinizing hormone.

(From Brown TA: Rapid Review Physiology. St. Louis, Mosby, 2007, p 99, Fig. 3-15.)

Proliferative phase: estrogen-mediated; most variable phase

b. Estrogen surge occurs 24 to 36 hours prior to ovulation.

(1) Stimulates luteinizing hormone (LH) release

• Positive feedback

(2) Stimulates follicle-stimulating hormone (FSH) release

(a) Positive feedback on FSH and LH

(b) Serum LH > FSH; greatest positive feedback on LH

(3) LH surge initiates ovulation.

Ovulation: estrogen surge → LH surge → ovulation

a. Occurs between days 14 and 16

b. Ovulation indicators

(1) Increase in body temperature

• Effect of progesterone

(2) Subnuclear vacuoles in endometrial cells (Fig. 21-11)

21-11: Subnuclear vacuoles (arrows) containing mucin push the nuclei of the endometrial cells toward the apex of the cell. Eventually the mucin passes the nucleus and enters the lumen marking the beginning of the secretory phase.

(From Kumar V, Fausto N, Abbas A: Robbins and Cotran’s Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 1081, Fig. 21-5B.)

Subnuclear vacuoles: sign of ovulation

(3) Mittelschmerz

• Peritoneal irritation from blood from the ruptured follicle

3. Secretory phase (see Fig. 21-10)

a. Progesterone-mediated

• Least variable phase of the cycle

Secretory phase: progesterone-mediated; least variable phase

b. Increased gland tortuosity and secretion

c. Edema of stromal cells

In fertility workups, endometrial biopsies are commonly performed on day 21 to see if ovulation has occurred. Presence of secretory endometrium on day 21 confirms that ovulation has occurred.

d. Changes occurring after fertilization

(1) Fertilization usually occurs in the ampullary portion of the fallopian tube.

(2) Fertilized egg spends 3 days in the fallopian tube.

(3) Fertilized egg spends 2 days in the uterine cavity.

• Implants in the endometrial mucosa on day 21

Arias-Stella phenomenon: exaggerated secretory phase that occurs in pregnancy

(4) An exaggerated secretory phase occurs in pregnancy.

• Called the Arias-Stella phenomenon

a. Initiated by drop-off in serum levels of estrogen and progesterone

(1) Signal for the endometrial cells to undergo apoptosis

(2) Newborn baby girls commonly have vaginal bleeding.

• Due to sudden drop of maternal hormones with delivery

Menses: drop in hormones initiates apoptosis

b. Plasmin prevents menstrual blood from clotting.

Newborn girls: may have vaginal bleeding

• Excess clotting is a sign of menorrhagia.

5. Functions of FSH

a. Prepares the follicle of the month

b. Increases aromatase synthesis in the granulosa cells

FSH: prepares follicle, aromatase synthesis, LH receptor synthesis

c. Increases the synthesis of LH receptors

6. Functions of LH

a. LH in the proliferative phase

(1) Increases the synthesis of 17-ketosteroids (KS) in the theca interna (see Fig. 21-9)

• 17-KS are dehydroepiandrosterone (DHEA) and androstenedione.

(2) DHEA is converted to androstenedione.

LH proliferative phase: synthesis of testosterone for conversion by aromatase into estradiol in granulosa cells

(3) An oxidoreductase converts androstenedione to testosterone.

(4) Testosterone enters granulosa cells and is aromatized to estradiol.

b. LH surge is induced by a sudden increase in estrogen.

• Ovulation occurs when LH > FSH.

c. LH in the secretory phase (see Fig. 21-9)

• Theca interna primarily synthesizes 17-hydroxyprogesterone (17-OH-progesterone).

LH secretory phase: synthesize 17-OH-progesterone

7. Hormone changes in pregnancy

a. Human chorionic gonadotropin (hCG)

hCG: LH analogue

(1) Synthesized in the syncytiotrophoblast lining the chorionic villus

(2) Acts as an LH analogue by maintaining the corpus luteum of pregnancy.

hCG: maintains corpus luteum of pregnancy for 8–10 weeks

(3) Corpus luteum synthesizes progesterone for ∼︀8 to 10 weeks.

b. Corpus luteum involutes after ∼︀8 to 10 weeks.

(1) Placenta synthesizes progesterone for the remainder of the pregnancy.

(2) Spontaneous abortion may occur if placental production of progesterone is inadequate.

C. Oral contraceptive pills (OCPs)

1. Mixture of estrogen + progestins (progesterone)

a. Baseline levels of estrogen prevent the midcycle estrogen surge.

• Prevents the LH surge and ovulation

OCP: prevents LH surge and ovulation; progestins cause gland atrophy

b. Progestins arrest the proliferative phase and cause gland atrophy.

c. Progestins inhibit LH, which also prevents the LH surge.

2. OCPs render the cervical mucus hostile to sperm.

3. OCPs alter fallopian tube motility.

D. Sources and types of estrogen

Estradiol: estrogen of a nonpregnant woman

a. Primary estrogen in nonpregnant women

b. Derived from aromatization of testosterone in granulosa cells

Estrone: estrogen of a postmenopausal woman

a. Weak estrogen produced during menopause

b. Derived from adipose cell aromatization of androstenedione

• Androstenedione is synthesized in the adrenal cortex.

Estrone: androstenedione from adrenal converted by aromatase to estrone

a. End-product of estradiol metabolism

b. Primary estrogen of pregnancy

• Derives from fetal adrenal, placenta, and maternal liver (refer section IX)

Estriol: estrogen of pregnancy

E. Sources and types of androgens

1. Androstenedione

• Equal derivation from ovaries and adrenal cortex

a. Mainly synthesized in the adrenal cortex (80%)

b. Remainder is synthesized in the ovaries.

3. DHEA-sulfate

• Almost exclusively synthesized in the adrenal cortex

DHEA-sulfate: almost exclusively synthesized in adrenal cortex

4. Testosterone

a. Derived from conversion of androstenedione to testosterone

Testosterone: synthesized in ovary and adrenals

b. Testosterone is synthesized in the ovaries and adrenal glands.

• Testosterone is peripherally converted to dehydroxytestosterone.

F. Sex hormone–binding globulin (SHBG) (Fig. 21-12)

21-12: Schematic of sex hormone–binding globulin (SHBG). See text for discussion. FT, free testosterone.

(From Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby Elsevier, 2008, p 366, Fig. 10-11.)

SHBG: synthesized in liver

1. Binding protein for testosterone and estrogen (refer to Chapter 20)

a. In both men and women, SHBG is primarily synthesized in the liver.

b. Estrogen increases synthesis of SHBG in the liver.

c. Androgens, obesity, hypothyroidism all decrease the synthesis of SHBG.

SHBG: higher binding affinity for testosterone than for estrogen

2. SHBG has a greater binding affinity for testosterone than estrogen.

a. Increased SHBG decreases free testosterone (FT) levels.

b. Decreased SHBG increases FT levels.

• Common cause of hirsutism in women (see later discussion)

SHBG: ↑ SHBG, ↓ FT; ↓ SHBG, ↑ FT

G. Normal changes in pregnancy

1. Plasma volume and RBC mass

a. Both are increased

• Increase in plasma volume > increase in RBC mass.

b. Causes a 1-g/dL drop in hemoglobin (Hb) (dilutional effect)

Pregnancy: ↑ RBC mass/↑↑ plasma volume = ↓ Hb and RBC count (dilutional effect)

c. Increases glomerular filtration rate (GFR)

(1) Creatinine clearance (CCr) is increased.

(2) Increased clearance of urea and creatinine

• Serum levels are at the lower limit of normal.

Pregnancy: ↑↑ plasma volume causes ↑ GFR and CCr

(3) Increases pressure to pump blood into the maternal lake in the placenta

2. Respiratory alkalosis

a. Effect of estrogen and progesterone stimulating respiratory center

b. Decrease in PaCO₂ causes a corresponding increase in PaO₂.

Pregnancy: respiratory alkalosis; estrogen/progesterone stimulation of respiratory center

3. Increased serum thyroxine (T₄) and cortisol

a. Estrogen stimulates synthesis of thyroid-binding globulin and transcortin.

b. Increased binding proteins increases total thyroxine and cortisol.

c. Metabolically active free hormone levels are normal (refer to Chapter 22).

• No clinical signs of overactivity

Pregnancy: ↑ serum T₄/cortisol; due to increase in binding proteins

H. Menopause

1. Epidemiology

a. Defined as no menses for 1 year after age 40

Menopause: no menses for 1 year after age 40

(1) Physiologic

(a) Waxing and waning of estrogen levels

• Due to decreased ovarian function

(b) Depletion of granulosa and thecal cells

(c) Lack of response to gonadotropins

(d) Increased LH stimulates androgen production in stromal cells

(2) Surgical removal/radiation of ovaries

(3) Turner’s syndrome (refer to Chapter 5)

(4) Family history of early menopause

(5) Left-handedness

c. Average age of menopause is 51 years old.

(1) Age at which it occurs is genetically determined.

(2) Smokers reach menopause earlier than nonsmokers.

(3) Onset of perimenopause is mid- to late 40s

2. Clinical findings

a. Secondary amenorrhea

b. Hot flushes, night sweats

Menopause: hot flushes, night sweats, mood swings

c. Atrophic vaginitis

• Pruritus, burning, bleeding, dyspareunia

d. Mood swings, anxiety, depression, insomnia

e. Decreased libido

f. Urinary incontinence (refer to Chapter 20)

g. Headaches, tiredness, lethargy

h. Osteoporosis (refer to Chapter 23)

• Increased risk for vertebral and Colles fractures

3. Laboratory findings

a. Increase in FSH and LH

Menopause: ↑ FSH best marker; absence of menses for 12 months

(1) Due to drop in estrogen and progesterone, respectively

(2) Serum FSH is the best marker.

b. Decreased serum estradiol

c. Serum FSH is the best marker.

a. Estrogen replacement if symptomatic

b. Progestin added if uterus is still present

• Prevent endometrial adenocarcinoma

c. Risks of long-term combined therapy

(1) Thromboembolism

(2) Coronary heart disease, stroke

(3) Slight risk for breast cancer

(4) Increased risk for dementia in women ≥ 65 years old

• Applies also if only taking estrogen

I. Hirsutism and virilization

1. Epidemiology and pathogenesis

a. Hirsutism is excess hair in normal hair-bearing areas (Fig. 21-13).

• Virilization is hirsutism + male secondary sex characteristics.

21-13: Hirsutism. A, This woman has excess hair above the lip and on the chin. B, A woman with a male distribution of hair from the mons pubis to the umbilicus.

(A from Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby Elsevier, 2008, p 369, Fig. 10-12; B from Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 1. London, Mosby-Wolfe, 1997, p 47, Fig. 93.)

Hirsutism: excess hair in normal hair-bearing areas

Virilization: hirsutism + male secondary sex characteristics

b. Male secondary sex characteristics

(1) Increased muscle mass

(3) Enlarged clitoris (clitoromegaly) (Fig. 21-14)

• Most important finding

c. Both conditions are due to increased androgens of ovarian or adrenal origin

21-14: Clitoromegaly. Note the elongation of the clitoris, which is the gold standard sign of virilization.

(From Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 1. London, Mosby-Wolfe, 1997, p 4, Fig. 7.)

Hirsutism and virilization: hyperandrogenicity of ovarian, adrenal, or drug origin

(1) Ovarian origin—testosterone (free testosterone; sometimes total) is primarily increased

(2) Adrenal origin—DHEA-sulfate and testosterone increased

(1) Polycystic ovary syndrome (see later discussion; 75%)

Hirsutism: polycystic ovary syndrome most common cause

(2) Idiopathic (5–15%)

(3) Adrenogenital syndrome (1–8%; refer to Chapter 22)

(4) Insulin resistance syndrome (3–4%; see section VIII)

(5) Drugs (<1%)

• Examples—androgenic progestins, phenytoin, cyclosporin, minoxidil

(6) Ovarian tumor (<1%; see section VIII)

• Leydig cell tumor, Sertoli-Leydig cell tumor

(7) Adrenal tumor (<1%)

• Adenoma/carcinoma producing Cushing’s syndrome

• Decreased SHBG causes an increase in free testosterone.

Hirsutism, ovarian cause: ↑ testosterone

(9) Hypothyroidism

2. Polycystic ovary syndrome (POS)

Hirsutism, adrenal cause: ↑ DHEA-S, testosterone

a. Epidemiology

(1) Occurs in 3% of adolescents and adults

(2) Symptoms begin around menarche.

(3) Increased risk of endometrial cancer

POS: increased risk for endometrial cancer

(4) Increased pituitary synthesis of LH and decreased synthesis of FSH

(a) Increased LH increases androgen synthesis.

• Hirsutism occurs more often than virilization.

(b) Androgens are aromatized to estrogen in the adipose cells.

POS: ↑ estrogen and androgens

• Increased estrogen increases risk for endometrial carcinoma.

(c) Increased estrogen has a positive feedback on LH and negative feedback on FSH.

(d) Suppression of FSH causes follicle degeneration.

(e) Fluid accumulation produces subcortical cysts that enlarge the ovaries (Figs. 21-15 and 21-16).

b. Clinical findings

(1) Menstrual irregularities

21-15: Polycystic ovary syndrome showing an enlarged ovary with multiple subcortical cysts.

(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 262, Fig. 13-17A.)

21-16: Polycystic ovary syndrome showing an ultrasound with an enlarged ovary demonstrating multiple subcortical cysts (arrows).

(From Pretorius ES, Solomon JA: Radiology Secrets, 2nd ed. St. Louis, Mosby, 2006, p 204, Fig. 24-7.)

POS: oligomenorrhea most common complaint

• Oligomenorrhea is the most common complaint.

(2) Hirsutism, infertility, obesity (40–50%)

c. Laboratory findings

POS: ↑ LH, ↓ FSH; LH:FSH ratio > 2

(1) LH:FSH ratio > 2

(2) Increased serum testosterone (free and total) and androstenedione

(3) Increased serum estrogen

a. Weight reduction in obese women

b. Low-dose OCPs or medroxyprogesterone

Rx of POS: low-dose OCPs or medroxyprogesterone

• Suppress ovarian steroidogenesis and LH

c. Spironolactone if OCPs unacceptable

• Block androgen receptors on hair follicle

d. LH-releasing hormone analogues

• Inhibit ovarian androgen production

J. Menstrual dysfunction

a. Loss of blood > 80 mL per period

b. Menorrhagia likely if:

(1) Staining of sheets at night with heavy protection

(2) Excessive passage of clots

• Indicates plasmin does not have enough time to dissolve clot

Menorrhagia: loss > 80 mL per period

2. Dysmenorrhea

a. Epidemiology

(1) Painful menses

(2) Approximately 50% of women have dysmenorrhea.

• Approximately 10% are incapacitated for 1 to 3 days.

(3) Primary type

(a) Only occurs in ovulatory cycles

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Tags: Rapid Review Pathology Revised Reprint

Jun 25, 2017 | Posted by admin in PATHOLOGY & LABORATORY MEDICINE | Comments Off

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