Reproductive Health Notes

Structure and Function of the Female Reproductive System

  • Assigned reading:
    • McCance, K.L. & Huether, S.E. (2019). Pathophysiology: The biologic basis for disease in adults and children (8th ed). Elsevier.
    • Chapters:
      • Chapter 24: Structure and Function of the Reproductive Systems
      • Chapter 25: Alterations of the Female Reproductive
      • Chapter 26: Alterations of the Male Reproductive System

Basic Anatomy of the Female Breast

  • Components:
    • Lymph nodes
    • Nipple
    • Areola
    • Chest wall
    • Ribs
    • Muscle
    • Fatty tissue
    • Lobe
    • Ducts
    • Lobules

Basic Anatomy of the Female Reproductive System

  • Components:
    • Uterine (fallopian) tube
    • Ovary
    • Fundus of uterus
    • Corpus (body) of uterus
    • Cervix
    • Vagina
    • Rectum
    • Urinary bladder
    • Symphysis pubis
    • Clitoris
    • Urethra
    • Labium majora
    • Labium minora
    • Endometrium
    • Myometrium

Hypothalamic-Pituitary-Gonadal Axis

  • The hypothalamic-pituitary-gonadal axis maintains control of secondary sex characteristics and the menstrual cycle.
    • Hypothalamus secretes gonadotropin-releasing hormone (GnRH).
    • GnRH travels to the anterior pituitary gland, stimulating the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
    • FSH and LH act on the ovaries to release estrogen and/or progesterone.

Menstrual Cycle

  • The first day of bleeding is considered the first day of the menstrual cycle.
    • Hypothalamic GnRH stimulates the release of pituitary FSH (LH is inhibited).
    • FSH acts to mature primary follicles into secondary follicles, which then release estrogen.
    • High levels of estrogen stimulate the release of LH.
    • LH spike causes the release of the oocyte from the most mature secondary follicle.
    • The secondary follicle becomes the corpus luteum, which secretes progesterone and estrogen.

Alterations of the Female Reproductive System

Anatomical Abnormalities
  • Abnormal cell development in the Mullerian tube can cause anatomical abnormalities of the uterus, cervix, and vagina.
    • 7% of women have some sort of anatomical uterine abnormality.
    • May be asymptomatic or manifest as menstrual abnormalities, sexual dysfunction, or infertility.
Acquired Anatomical Abnormalities
  • Pelvic organ prolapse is a disorder in which the perineal muscles (levator ani group) lose tone and strength during the process of aging.
    • Loss of muscle tone, the forces of gravity, and the outward forces of the abdominal cavity cause the bulging of organs into the vaginal wall.
    • Severe cases may have bulging of organs through the vaginal opening.
    • Increased risk with vaginal pregnancies and hysterectomies.
    • Occurs in 50% of women; however, most cases are completely asymptomatic.
    • Worsening prolapse manifests as increased vaginal pressure and can cause dysfunction of the affected organ.
  • Treatment:
    • Kegel exercises to strengthen the pelvic floor.
    • Surgery if severe.
  • Types:
    • Uterine prolapse: Bulging of the cervix or uterus into the vaginal canal.
    • Cystocele: Bulging of the posterior bladder wall into the vaginal canal.
    • Rectocele: Bulging of the rectal wall into the vaginal canal.
    • Enterocele: Herniation of the rectouterine pouch into the rectovaginal septum (between the rectum and the posterior vaginal wall), i.e., bulging of the small intestine into the vaginal canal.
Alterations of Sexual Maturation

  • Delayed Puberty: Delayed development of secondary sex characteristics.

    • No development of breasts (thelarche) by age 13.
    • No development of menses (menarche) by age 15 - 16.
    • Development of pubic hair (pubarche) is typically not affected.
    • Most cases of delayed puberty are physiological/constitutional.
      • Normal hormones and HPA/HPO axis slow to mature.
      • Typically familial.
      • Diagnosed retrospectively after patients have progressed to puberty (occurs spontaneously in 30% of patients with delayed puberty).
    • Some cases are due to an underlying condition or illness.
      • Functional hypogonadotropic hypogonadism, CNS tumor, Turner’s syndrome, etc.
    • Delayed puberty may cause psychosocial issues and increase the risk of inadequate bone density development due to a lack of estrogen.
    • Need to find and treat the underlying cause; can give hormone replacement.

  • Precocious Puberty: Clinical onset of puberty before the age of 8.

    • Due to recent trends of earlier onset puberty in the general population, some pediatricians suggest lowering the age for precocious puberty and separating based on ethnicity (age of 6 in black girls and age 7 in white girls).
    • May be due to a factor of genetics, obesity, and increased protein consumption.
    • May be due to underlying condition or illness.
      • CNS, ovarian, or adrenal tumors.
    • Precocious puberty may cause psychological issues and increase the risk of short stature due to closure of the epiphyseal growth plate.
    • Need to find and treat underlying cause.
      • May give GnRH agonist analogs to suppress the HPG axis and delay puberty.
Dysmenorrhea
  • Dysmenorrhea means painful menstruation.
  • Two main categories of dysmenorrhea:
    • Primary dysmenorrhea
      • Pain is caused by the release of prostaglandins in the ovarian cycle; no underlying pelvic disease.
    • Secondary dysmenorrhea
      • Pain is caused by underlying pelvic disease (ovarian cyst, endometriosis, adenomyosis, etc.).
Amenorrhea
  • Amenorrhea means lack of menstruation.
  • Two main categories of amenorrhea:
    • Primary amenorrhea
      • Failure to develop menses as well as secondary sex characteristics by age 13.
      • Failure to develop menses by age 15 regardless of secondary sex characteristics.
      • Definition is similar to delayed puberty, but diagnosis suggests pathological etiology.
    • Secondary amenorrhea
      • Previous menstruation; however, absence of regular menses for 3 months or irregular menses for 6 months.
Primary Amenorrhea
  • Primary amenorrhea can be classified based on “compartments.”
    • Compartment I: Anatomic defects of the outflow tract
      • Ex: Normal ovaries but congenital absence of vagina or uterus.
    • Compartment II: Ovarian disorders
      • Ex: Gonadal dysgenesis; often linked with genetic defects.
    • Compartment III: Disorders of the anterior pituitary gland
      • Ex: Pituitary dysregulation (tumor, traumatic brain injury).
    • Compartment IV: Disorders of the central nervous system (CNS) or hypothalamic factors
      • Ex: Hypothalamic dysregulation (tumor, stress, anorexia, infection, traumatic brain injury).
Secondary Amenorrhea

  • What is the most common cause of secondary amenorrhea?

    • Must always rule this out first before working up the cause of secondary amenorrhea!

  • Other potential causes of secondary amenorrhea include:

    • Thyroid dysfunction, anovulation (hyperprolactinemia, pituitary gland dysfunction, excess stress or exercise, excess weight loss or low body weight, polycystic ovarian disease), or structural (Asherman syndrome, hysterectomy, etc).
Premenstrual Disorders

  • Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD)

    • Distressing physical, psychological, or behavior changes that impair interpersonal relationships or interfere with usual activities.
      • Changes are cyclic and associated with the luteal phase of menstruation.
      • Symptoms resolve with menstruation (may last up to four days).
    • Thought to be due to hormonal changes, interactions with neurotransmitters (serotonin, GABA), and the renin-angiotensin-aldosterone pathway.
    • Clinical manifestations:
      • Physical symptoms: abdominal bloating, breast tenderness, headache, extremity swelling.
      • Psychological symptoms: depression, anxiety, irritability, fatigue.
      • Symptoms must be severe enough that they are interfering with daily life.

  • Treatment

    • First-line treatment is non-pharmacological and includes cognitive behavior therapy, lifestyle modification (regular exercise, appropriate sleep, stress reduction), as well as integrative medicine (can consider acupuncture, calcium supplementation).
    • More severe cases may need anti-depressant medications.
Abnormal Uterine Bleeding
  • Bleeding that is abnormal in duration, volume, frequency, or regularity for the majority of the previous 6 months
  • Normal menses should be every 28 days ±\pm 7 days, and the duration of menses should be 7 days or less.
  • Examples of abnormal uterine bleeding include irregular bleeding/spotting, heavy menstrual bleeding, or intermenstrual bleeding.
  • Acronym PALM-COEIN can be used to find out underlying cause of uterine dysfunction.
  • Must rule out other causes
    • Abortion or miscarriage, complicated pregnancy, ectopic pregnancy, etc.
  • The acronym PALM-COEIN can be used to identify the cause of abnormal uterine bleeding.
Polycystic Ovary Syndrome
  • Most common cause of anovulation and ovulatory dysfunction; leading cause of infertility in the US
  • Strong genetic component and complex pathophysiology that isn’t fully understood
    • Insulin resistance leads to increased ovarian production of androgens and disordered FSH/LH
  • Must have at least two of the following symptoms:
    • Irregular ovulation, elevated androgens, or appearance of polycystic ovaries on ultrasound
  • PCOS is also associated with metabolic disorder (high cholesterol levels, obesity, and insulin resistance)
  • 3x increased risk of developing uterine cancer later and 9x increased risk of endometrial cancer in life due to anovulation and unopposed estrogen
  • Clinical manifestations
    • Symptoms typically appear within 2 years of puberty but may take longer and may not present at all until pregnancy
    • Symptoms are caused by anovulation, hyperandrogenism, and insulin resistance
  • Treatment
    • Goals of treatment include instituting regular menstrual cycles, relieving symptoms of hyperandrogenism, and improving insulin sensitivity
    • Medications include oral contraceptives for management of symptoms (acne, hirsutism, and painful periods)
    • Lifestyle modifications (regular exercise and maintain healthy weight)
Vaginitis
  • Inflammation of the vagina; most often caused by infection but can also be caused by chemical or mechanical irritants and pathologies
  • Infectious etiologies include:
    • Overgrowth of normal flora (bacterial vaginosis)
    • Overgrowth of Candida albicans (yeast infections)
    • Sexually transmitted infections (gonorrhea, chlamydia, etc.)
  • Normal vagina produces acidic secretions to provide protection against infection
    • Secretions more neutral before puberty, after menopause, and during pregnancy
    • The use of soaps, feminine hygiene sprays, deodorant menstrual pads/tampons can alter this pH balance and increase the risk of infections
  • Clinical manifestation
    • Copious, malodorous, or irritating discharge
      • Note that vaginal secretions may change throughout the menstrual cycle; clear, milky, and cloudy secretions may be normal; however, abrupt changes and foul odor are signs of an infection
  • Treatment
    • Administer antimicrobial or antifungal medications
      • Treat partners if STI
    • Administer probiotic supplements if needed
Cervicitis
  • Inflammation of the cervix; may by infection, chemical or mechanical irritants, or other pathologies
    • Consider age in differential diagnosis (younger sexually active women should be screened for STIs; consider menopausal changes for older women)
  • Hallmark signs: purulent discharge from cervical os or endocervical bleeding
  • Treatment
    • Treat underlying cause
Pelvic Inflammatory Disease
  • Acute inflammation of organs in the upper genital tract
    • Salpingitis: inflammation of the fallopian tubes
    • Oophoritis: inflammation of the ovaries
    • May also spread to uterus and the peritoneal cavity
  • Caused by infectious etiology
    • Sexually transmitted infections (especially gonorrhea and chlamydia) or normal flora that migrate from the vagina to the upper genital tract
  • Clinical manifestations
    • May be asymptomatic in mild cases
    • More often presents with sudden onset severe abdominal pain, fever, dysuria (pain with urination), pain with sexual intercourse, irregular bleeding, or abnormal discharge
  • Evaluation
    • Sexually active women who have abdominal or pelvic tenderness and one of the following signs: cervical motion tenderness, uterine tenderness, adnexal tenderness
  • Treatment
    • Empiric broad-spectrum antibiotics (cover polymicrobial infections)
    • Treat sexual partners as well, given the risk of STIs
  • Complications
    • Increased risk of infertility due to inflammatory changes/scarring
    • Increased risk of ectopic pregnancies
Benign Growths/Tissue Proliferation
  • Benign ovarian cysts
    • Commonly occur during hormonal imbalances
    • May be follicular, corpus luteum, or dermoid cysts (malignant potential)
  • Endometrial polyps
    • Benign mass of endometrial tissue
  • Leiomyoma
    • Uterine fibroids; benign mass of myometrial tissue
    • Can cause abnormal uterine bleeding, pain, and pressure
  • Adenomyosis
    • Presence of endometrial tissue within the myometrium
    • May be asymptomatic or cause abnormal menstrual bleeding, pain, and infertility
  • Endometriosis
    • Presence of functioning endometrial tissue outside of the uterus (may be on ovaries, pelvic peritoneum, and uterosacral ligaments)
    • Symptoms vary in severity and frequency
    • infertility, abnormal bleeding, heavy bleeding, pelvic pain, pain with urination, pain with defecation, pain with intercourse
Cervical Cancer
  • Caused exclusively by the Human papillomavirus (HPV) infection
    • Most sexually active women will have HPV during some point in their lives; most will be asymptomatic and resolve spontaneously
    • Infection with HPV may cause precancerous changes to cervical cells (cervical dysplasia), which may then process to precancerous cervical intraepithelial carcinoma and then cervical carcinoma in situ
    • HPV may also cause anal, vaginal, vulvar, and penile cancers
  • Standard screening with Papanicolaou (Pap) tests to look for cervical cell abnormalities or HPV tests
  • Symptoms of cervical cancer include irregular bleeding or discharge
  • Vaccine (Gardasil) against HPV available in the United States since 2006
Breast Cancer
  • Note that there are multiple different types of breast cancer, depending on the type of cell affected
    • Carcinoma of mammary ducts, infiltrating carcinoma, carcinomas of mammary lobules, sarcoma of breast
  • Second most common cancer in women
  • 2/3 of cases occur in women >55 years old
  • Increased risk in younger “high risk” women
    • Positive family history of breast or ovarian cancer diagnosed at <45 years of age
    • BRCA1 or BRCA2
    • Ethnicity
    • Increased breast tissue density
    • Increased estrogen exposure (early periods, late menopause, oral contraceptive use)
    • Nulliparous (no pregnancy) or late first pregnancy
    • Exposure to radiation
    • Obesity and tall height
    • Smoking, etc.
  • Hormones can greatly affect the risk of developing breast cancer
    • Increase risk: Estrogen, progesterone, prolactin, growth hormone, insulin-like growth factor
    • Decrease risk: human chorionic gonadotropin (hCG).
  • Clinical manifestations include:
    • Most cancers will occur in the upper outer quadrant
    • Most common first sign of breast cancer is a painless lump
    • Dilated blood vessels, dimpling of the skin, edema of breast tissue, fixed lymphadenopathy, edema of arm, nipple or alveolar eczema, nipple discharge in nonlactating woman, bloody discharge, nipple retraction, pitting of the skin (peau d’orange or “like an orange peel”), breast erythema/tenderness/warmth, and breast ulceration
    • Metastasis can occur to vertebra, pelvic bones, ribs, skull, lungs, kidneys, liver, adrenal glands, ovaries, and brain
      • May see symptoms of metastasis such as chest pain (lung), pathologic vertebral fracture (vertebra), etc.

Case Studies

Case Study 1

  • A 29-year-old female presents to the clinic with complaints of missed periods. The patient states she has had irregular periods her whole life, but recently they have become more irregular, and now she is skipping months. In the past year, she has only had 4 periods. The last menstrual cycle was 3 months ago.
  • Physical exam demonstrates a healthy-appearing woman who is slightly overweight. The patient does have some cystic-appearing acne over her jawline.
    • Is this considered amenorrhea?
    • Is this considered primary or secondary amenorrhea?
  • What is the first test that we should perform on this patient?
    • A. Check thyroid levels (TSH, T3, T4)
    • B. Check for polycystic ovarian disease
    • C. Pregnancy test
    • D. Complete blood count
  • The following labs are obtained:
    • Urine pregnancy test is negative.
    • Thyroid panel (TSH, T3, T4) is normal.
    • Testosterone and androgen levels are elevated.
    • HbA1c is concerning for pre-diabetes.
    • Pelvic ultrasound demonstrates a normal uterus and ovaries.
  • What is the most likely diagnosis?
    • A. Endometriosis
    • B. Polycystic ovarian disease
    • C. Leiomyoma
    • D. Pelvic inflammatory disease

Case Study 2

  • A 17-year-old female presents to the emergency department with complaints of fever and lower abdominal pain. The patient states that she is sexually active, on oral contraceptives, and does not use barrier protection methods.
  • Patient has been experiencing pain with urination and abnormal foul-smelling vaginal discharge.
  • Vitals are significant for elevated temperature (39 C), increased HR (114), and low blood pressure (90/50).
  • Labs are significant for high WBC (13k).
  • Physician exam is significant for cervical motion tenderness.
  • Based on the vitals, labs, and history, what is the most likely diagnosis in our patient?
    • A. Vaginitis
    • B. Bacterial vaginosis
    • C. Cervicitis
    • D. Pelvic inflammatory disease
  • Based on the clinical history, what is the most likely pathogen causing infection?
    • A. Overgrowth of normal bacterial flora
    • B. Sexually transmitted disease
    • C. Fungal (Candida albicans)
    • D. Both A and B
  • Patient is admitted to the hospital and improves after 3 days of treatment. Prior to discharge, what important patient education should be given to our patient on the prevention of this disease?