Pathopharm II- Female Reproductive system disorders

Dysmenorrhea

Painful menstrual periods

Dysfunctional uterine bleeding (DUB)

AKA: Abnormal uterine bleeding

Premenstrual syndrome (PMS)

Signs and symptoms present before menstruation.

•Physical, emotional, behavior changes prior to menstrual cycle

‒50% of women have mild to moderate PMS

‒Abnormal response to neurotransmitters prior to menstruation

•Treatment with selective serotonin receptor inhibitors (SSRIs) have been helpful to regulate emotional changes.

Menorrhagia

Excessive menstrual blood loss

Menopause

Physiological cessation of ovulation and menstrual cycles Process begins on average age 51 years

Follicular phase

FSH stimulates ovarian follicles to produce estrogen

Days 1–14

FSH- gets everything ready to go.

Ovulation

Positive feedback by estrogen causes surge in FSH/LH

Ovum released from ovary

Day 14

Menstrual cycle involves

Approximately 28 days (may be longer or shorter depending on individual)

Follicular phase, Ovulation, Luteal phase

Estrogen-Stimulates uterine lining growth for implantation

Progesterone-Stabilizes uterine lining for implantation

Fertilization does not occur-Corpus luteum degenerates, Progesterone levels fall, Uterine lining shed

Luteal phase

Corpus luteum forms and produces progesterone

Days 14–28

phase- hope for fertilizations or get bleeding

Menarche

1st episode menstrual bleeding, typically 12-13 years old. 8-9 could indicate precocious puberty or endocrine disorder.

Menses

Menstrual bleeding

Menopause

No menses for a year!

•Permanent cessation of menstrual cycles

•Perimenopause: Gradual decline in ovarian function, time frame leading to menopause.

•Atrophic vaginitis, vasomotor instability

•Low estrogen, high FSH

Thelarche

•Development of breast tissue

•Occurs at about the same time as first menstrual period as part of puberty.

Breast lobules

•Drain into lactiferous duct

•Lactiferous duct empties into nipple surface

Prolactin

Milk formation

Oxytocin

Milk release

Precocious Puberty

under 8 or 9 years old

European American: <8 years

Hispanic/African American: <7.5 years

-Central: Hypothalamus-pituitary involvement

-Peripheral: Ovaries, testes, adrenal glands

Delayed Puberty

By age 13, lack of secondary sex characteristics. Over age 13.

Genetic causes

Constitutional growth delays

Other causes: Chronic illness, eating disorders, strenuous exercise

Infertility

Failure to achieve pregnancy within 12 months (1 year)

•Unprotected intercourse

•Therapeutic donor insemination in females <35 years

Male biggest cause is issue with sperm- amount, if mature

Women biggest cause is structural issues

Polycystic ovarian syndrome (PCOS)

Overproduction of androgens

Ovary does not release ovum

Premature ovarian failure (POF)

Body develops antibodies against ovarian tissue

Endometriosis

Uterine tissue outside the uterus

Fallopian tube damage

Ectopic pregnancy, infection, or inflammation

Cervical obstruction

Inherited malformation of damage to cervix

Uterine fibroids

Disrupt implantation

Amenorrhea

•Absence of menstrual period

•Pregnancy must be ruled out

Tend to be younger, lack of estrogen, progresterone

-Illness, athletes training a lot, signs of eating disorders.

Primary amenorrhea

•Menses does not occur before age 16

•Often congenital, unrecognized until puberty

•Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH)

•Uterus absent and vagina foreshortened, normal ovaries.

Dysmenorrhea

•Painful periods

•75% of 15- to 25-year-olds

•Prostaglandin release (particularly prostaglandin F)

Diagnosis- Rule out pelvic pathologies (infection), or structural issues.

-Indicate Dysmenorrhea- pain that does not go away with medication, pain that interferes with daily life.

Treatment- Oral contraceptives and Anti-prostaglandins

Premenstrual dysphoric disorder (PMDD)

‒More severe form of PMS, interferes with work, school, social activities, and relationships, depressed mood

Menorrhagia

Excessive menstrual bleeding

Menses lasts greater than 7 days

Metrorrhagia

Excessive uterine bleeding

Both at time of normal menstrual period and more frequently- and in between, not really going through cycle.

Oligomenorrhea

Infrequent periods

Prolonged time between periods. Takes longer to get menses cycle, infrequent and irregular

Sexual history (5 Ps)

•Partners- if have multiple or just one

•Practices

•Prevention of STIs

•Past history of STIs

‒Gonorrhea, chlamydia, genital herpes, human papillomavirus, syphilis, and HIV

• Pregnancy prevention- oral contraceptives, IUD

Papanicolaou smear (Pap smear)

Cervical cancer cellular changes, annule exam, screen for cervical cancers, Biopsy

Liquid-based cytology (LBC)

Study Cervical cell changes for cancer, HPV

Colposcopy

Visualize cervix, camara to visualize

Culdoscopy

Visualize uterine tubes and ovaries, camara to visualize

Carcinoembryonic antigen 125 (CA-125)

Marker associated with uterine fibroids, endometriosis, ovarian cancer, Tumor markers, blood draw

Hysteroscopy

Visualize interior of uterus, camara to visualize

Laparoscopy

Small surgical incision, view internal organs, camara to visualize

Mammography

Specialized x-ray to visualize breast tissue

Hormone replacement therapy (HRT)

Menopausal symptoms, prevent and slow down.

Weigh risk and benefits, give more estrogen

Excessive estrogen can cause cadiovascular issues, clotting issues and many other issues

What do Fertility drugs do?

Stimulate ovulation

In vitro fertilization (IVF)

Pregnancy, structural issues or want to have own child, healthy sperm, and low sperm count

Dilation and curettage (D & C)

Dilate cervix, surgical removal of lining of uterus, usually with ecptopic pregnancy, not abortions.

Hysterectomy

Surgical removal of uterus

Endometrial ablation

Removal of uterine lining

Cryosurgery

Remove portion of cervix for diagnosis for biopsy

NEVER MIX WITH ESTROGEN with

SMOKING.- vasoconstriction and puts women at higher risk for stroke.

What is Endometritis??

Infection of endometrosis- SOAP BOX

Usually a mixed infection

•Often ascending from vagina

•Gonococcus, Chlamydia trachomatis, Enterococcus

•May occur in conjunction of infection of other tissues

Symptoms= Vaginal bleeding, uterine tenderness, fever, malodorous discharge

Treatment- Antibiotics

What is Endometriosis?

Endometrial tissue that has been moved.

•Growth of endometrial tissue outside of uterus

•~15% of women

•~80% of women with pelvic pain

•Ovaries, uterine ligaments, pelvic peritoneum,

•Displaced tissue responds to hormonal signals, causing bleeding, pain, infertility

•Biggest problem- infertility, Still responds to hormonal signals and continues to swell and bleed into body cavities.

Adenomyosis

•Endometrial tissue growing inside the muscle layer of the uterus

What are causes of Endometrosis?

Regurgitation/implantation= Endometrial tissue forced up through uterine tubes and into pelvic cavity.

Metaplastic= During embryological development, endometrial tissue appears in abnormal areas, placed wrong.

Vascular or lymphatic= Endometrial tissue metastasized to other areas.

Immunological= Displaced endometrial tissue triggers an autoimmune attack, body attacks it.

Environmental toxicity= Associated with some chemicals (dioxin).

How is Endometriosis diagnosed and treatment?

Definitive diagnosis: Laparoscopy

Treatment

•NSAIDs: First-line- try to control inflammation, Combined oral contraceptives and oral progestins- to regulate period. Progestin-only

•Long-acting GnRH agonists

•GnRH antagonists

•Aromatase inhibitors- prevent excessive estrogen

•Selective progesterone receptor and selective estrogen receptor modulators (SERMs)

•Surgery (not curative)- Remove pieces of tissue, trying to control

Endometrial Polyps

Neoplastic growth, unknown origin

•Usually benign – polyps are benign mucosal tumors.

•Postmenopausal females, vaginal bleeding, highest risk of for malignancy

Diagnosis: 3D color Doppler transvaginal ultrasound, hysteroscopy, biopsy

Treatment= Hysteroscopic surgical polypectomy- to remove polyps

•Hysterectomy recommended with atypical findings

Leiomyomas

Commonly known as fibroid tumors

•75% of women at some point in their lives, May regress at menopause (get better/change in size), Myometrium

•Most asymptomatic, If signs/symptoms present: Bleeding, pain, infertility

Diagnosis: Ultrasound

Treatment: Surgical excision, GnRH

Abnormal Uterine Bleeding

Presents with; Varies, Excessive blood loss, Lack of normal menstruation.

Causes- Vary with age= Adolescents, perimenopausal women: Anovulation, Increasing with age: Structural lesions, malignancies

Anovulatory- Immature hypothalamic–pituitary–ovarian axis.

Ovulatory- Excessive uterine bleeding can occur

Defects in the control mechanisms of menstruation

Abnormal Uterine Bleeding: Assessment and Diagnosis- Treat cause

Rule out pregnancy (b-hCG), Hemodynamic instability and anemia, Identify bleeding source

Blood tests=Complete blood count, Coagulation factors, clotting times, Hormone levels

Determine if following present: Primary ovarian insufficiency, Ovarian tumor, Perimenopause, PCOS.

Rule out: if infrequent, Eating disorders, Certain medications

Testing: Pelvic examination, Cervical cancer screening, Ultrasound, Hysteroscopy, Saline infusion sonohysterography

Abnormal Uterine Bleeding: Treatment

Hemodynamically unstable patients- bleeding out- MEDICAL EMERGENCY

•Uterine tamponade using a Foley catheter or gauze packing

•IV tranexamic acid

Hemodynamically stable

•Hormonal regulation

Surgery

Uterine Prolapse

Protrusion of uterus into vagina- uterus protrudes into vaginal opening.

Multiparous women

Degrees of prolapse

Pessary- Supportive device that is inserted to hold uterus in position- keep uterus in place.

Cause and Treatments for Uterine Prolapse?

Causes: usually age related

•Injury to the levator ani muscle or local nerves

•Pelvic masses, obesity, chronic constipation, connective tissue disorders

•Menopause: Reduced estrogen

Treatments: Kegel exercises- to help gain muscle tone. Native tissue repair without synthetic mesh, Transvaginal hysterectomy, Manchester-Fothergill surgical procedure‒Which is a uterine-preserving technique

Cystocele

Herniation of urinary bladder into vaginal canal. The bladder can have a tear and open into vaginal canal

Rectocele

Herniation of rectum into vaginal canal

Enterocele

Herniation of intestine between uterine ligaments

Herniation treatment

Surgical intervention

Nabothian cysts

In the Cervix Blockage of mucus-secreting gland in endocervix

•Common, benign, no treatment needed

Cervicitis

•Inflammation of cervix

•Ascending infection from vagina

•Erosion and epithelial cell changes apparent

Cervical polyps

•Usually benign, inflammatory changes of endocervix

•May cause postcoital bleeding, usually after sex

Prevention of Cervical Cancer includes?

High-risk types of human papillomavirus

•hrHPV

•Strains HPV 16 (most carcinogenic) and HPV 18

HPV infections- Different strans, Common

•Most resolve without clinical consequence

Risk factors: Smoking, immunocompromised state, HIV

HPV Vaccination done to Prevent Cervical Cancer are done at?

•2-dose schedule

‒Initiating vaccination at ages 9 to 14 years

•3-dose schedule

‒Initiating at ages 15 to 26 years

Immunocompromised

Vulvodynia

Pain of the vulva

Yeast infection, chemical irritants, infection

Vulvar cancer

Rare

Bleeding, itching, palpable mass, tenderness

Bartholin cyst or abscess

Small spherical structures at entry to vagina

Release secretions, can become infected

Antibiotics

Genitourinary syndrome of menopause (GMS)

AKA: Atrophic vaginitis

Inflammation of vagina after menopause

Caused by low estrogen

Low-dose vaginal estrogen treatment

Vaginitis

•Inflammation of vagina

‒Discharge, burning, itching

‒Pain with urination, sexual intercourse

•Bacterial causes (40% to 45%), vaginal candidiasis (20% to 25%), trichomoniasis (15% to 20%)

•Precise identification of organism is crucial to treatment

•Preventive measures‒Proper hygiene, avoidance of feminine deodorants and douches

Premature Ovarian Insufficiency (POI)

Cessation of ovarian function in women less than 40 years of age

Genetic, autoimmune

Irregular menstrual cycles, infertility, hot flashes

CVD, cognitive decline

Elevated FSH Other reproductive hormones

HRT Transdermal or transvaginal estradiol therapy

Follicular cyst

•Failure to eject ovum during ovulation

•Usually asymptomatic, spontaneous regression

Corpus luteum cyst

Occurs after ovulation

Usually causes symptoms, may rupture

•Pelvic pain, amenorrhea, followed by irregular or heavy bleeding

•Ultrasound confirms diagnosis, Rule out pregnancy, Laparotomy may be necessary to remove cyst

-Very painful, 1^st rule out appendencitis, begin. If happen a lot may need to control with contraceptives

Ovarian Torsion

Twisting of ovary

Obstructed blood flow

Severe, unilateral pain

May suspect GI issue (nausea/vomiting)

Rule out: Ectopic pregnancy

Ultrasound with color Doppler

Surgical removal Salvageable detorsion

Ovarian Teratoma

AKA: Dermoid cyst

Various embryonic tissues

Often benign

Symptomatic with complications

Blood testes (AFP, CA-125, b-HCG, etc.)

Imaging studies

Surgical excision

Polycystic Ovarian Syndrome (PCOS)

Autosomal dominant genetic disorder

•Women: Puberty to age 30 years

•Most common endocrine disturbance in young women

•Leading cause of infertility in the United States

Anovulation- Follicular cysts, Hypothalamic-pituitary-ovarian axis dysfunction.

Androgen excess, anovulation, hyperinsulinemia

Diagnostic criteria- Different specialty societies have varying criteria

‒Biochemical or clinical hyperandrogenism 

‒Ovulatory dysfunction

Evaluate for insulin resistance, T2DM

Treatment of Polycystic Ovarian Syndrome (PCOS)

•Reverse androgen excess

•Stimulate cyclic menstruation

‒Oral contraceptives

•Restoring fertility

•Ameliorate endocrine disturbances

‒Insulin sensitizers

Ectopic Pregnancy

Fertilized ovum implants outside the uterus

•98% occur in fallopian tubes

•Pain, vaginal bleeding, and amenorrhea are present

•Low level hCG (pregnancy hormone)

•Culdocentesis‒Will reveal blood if rupture

•Laparoscopic salpingostomy‒Remove ectopic pregnancy

Salpingectomy required if rupture

Fibrocystic breast disease

•Largely benign

•Female: 35 to 50 years of age

•Granular breast masses‒Prominent in second half of menstrual cycle

•Tenderness, vascular engorgement, and cystic distention‒Dissipates with menses

Fibroadenoma

•Benign breast mass

•Female: 25 to 45-year-olds

•Premenopausal women

•May indicate increased risk for breast cancer

•Single, “rubbery” mass

Mastitis

•Inflammation of breast, most commonly occurs with lactation

Galactorrhea

•Secretion of breast milk in non-lactating breast

•May be caused by prolactin-secreting pituitary tumor

Galactography or mammary ductography

Mammary duct ectasia

•Inflammation in subareolar ducts

•Common in postmenopausal women

•Small, calcified mass

Biopsy usually performed

Mammoplasty

Aesthetic surgery of the breast

Mastopexy

Shape of the breast and lifts the breast

Mammoplasty-augmentation or mammoplasty-reduction

Size of breast

Prophylactic Mastectomy: Prevention of Breast Cancer

Mutations in BRCA1 and/or BRCA2 genes

•Risk estimates are extremely heterogeneous

•Multiple strategies

‒Surveillance

‒Chemoprevention

‒Bilateral salpingo-oophorectomy

‒Risk-reducing mastectomy

What is a Gynecological emergency?

Ovarian torsion- May present similarly to appendicitis

Diagnosis of ectopic pregnancy

•Considered whenever a female of reproductive age complains of abdominal or pelvic pain

Therapeutic actions of Estrogens?

•Affect release of FSH and LH, Cause capillary dilation, fluid retention, and protein anabolism and thin the cervical mucus

•Conserve calcium and phosphorus and encourage bone formation. Inhibit ovulation

•Prevent postpartum breast discomfort, Responsible for the proliferation of the endometrial lining

•Absence of or decrease produces signs and symptoms of menopause, Compete with androgens for receptor sites

Systemic effects caused by Estrogens?

positives about estrogen replacement

•Protecting the heart from atherosclerosis

•Retaining calcium in the bones

•Maintaining the secondary female sex characteristics

Indications for Estrogens?

•Hormone replacement therapy (HRT)

•Palliation for discomforts in first few years of menopause

•Treat female hypogonadism and ovarian failure

•Prevent postpartum breast engorgement

•Part of combination contraceptives

•Slow bone loss in osteoporosis

Palliation in certain cancers

Pharmacokinetics for Estrogens?

•Well absorbed through the GI tract

•Undergo extensive hepatic metabolism, excreted in urine

•Cross placenta and enter human milk

•Available in multiple forms

Contraindications for Estrogens?

•Allergies and pregnancy

•Idiopathic vaginal bleeding, breast cancer, and estrogen-dependent cancer, thromboembolic disorders

•Undiagnosed atypical vaginal bleeding, Breast cancer or any estrogen-dependent cancer

•History of thromboembolic disorders, Heavy smoking, Hepatic dysfunction

•Pregnancy, Breast or chestfeeding

Cautions for Estrogens?

•Metabolic bone disease

•Renal insufficiency

•Hepatic impairment

Adverse effects for Estrogens

•GU effects

•Systemic effects

•GI effects