Female Reproductive System

• Patients with a personal (or family) history of breast, ovarian, prostate, or pancreatic cancer may benefit from hereditary cancer risk evaluation (genetic counseling) to determine risk for these cancers.

• BRCA1 and BRCA2 are inherited in an autosomal dominant pattern.

• Up to $6\%$ of breast cancer and $20\%$ of ovarian cancer cases are caused by BRCA1/BRCA2 mutations.

• Some ethnic groups are at higher risk for BRCA mutations.

• Men with BRCA mutations are at higher risk of breast cancer and prostate cancer.

• Women with a high lifetime risk (risk ≥$20\%$) should undergo:

  • annual screening mammogram

  • annual breast MRI

  • clinical breast exam every $6\text{ to }12\text{ months}$ starting $10\text{ years}$ before the age at diagnosis of the youngest affected family member.

• Practical screening rule: ask, “At what age were family member(s) diagnosed with breast cancer?” and screen $10\text{ years earlier}$. Example: if a sister was diagnosed at age $35$, begin MRI screening at age $25$.

Dominant Breast Mass/Breast Cancer

• Adult to older female with a dominant mass on one breast that feels hard and irregular; may be attached to skin/tissue or immobile.

• Common location: upper outer quadrant (tail of Spence).

• Skin changes: peau d’orange (orange-peel), dimpling, retraction.

• Nipple changes: may have painless or serous/bloody discharge; nipple may be displaced or fixed.

• Diagnostic approach:

  • order diagnostic mammogram with ultrasound

  • refer to breast surgeon if needed

  • note up to $15\%$ of women with breast cancer will have a negative mammogram; ultrasound can detect the mass

  • refer for diagnostic biopsy if indicated

• Metastatic sites (common):

  • bone (e.g., back pain)

  • liver (jaundice, abdominal pain, anorexia, nausea)

  • lungs (dyspnea, cough)

  • brain (headache)

Ectopic Pregnancy

• Reproductive-age, sexually active female with pelvic pain (diffuse or unilateral) ± vaginal bleeding.

• Pain onset usually early in the first trimester; can be dull or sharp (not typically crampy).

• If intraperitoneal bleeding, pain may radiate to the shoulder; patient may shuffle to reduce pelvic jarring.

• Reports amenorrhea to light menses in the prior $6-7\text{ weeks}$.

• Risk factors: prior ectopic, current IUD use, tubal ligation, IVF.

• Majority occur in the fallopian tube.

• Definite diagnosis: serum quantitative hCG and transvaginal ultrasonography.

Inflammatory Breast Cancer (IBC)

• Recent/acute onset of a red, swollen, warm area in the breast of a middle-aged woman (median age $59$) with rapid growth.

• Symptoms develop quickly; may have breast tenderness or itching; may mimic mastitis; often no discrete lump.

• Skin may be pitted (peau d’orange).

• Suspect in breast inflammation that does not respond to antibiotics.

• Prognosis: most IBC has lymph node metastases; ~1/3 have distant metastases at diagnosis.

• Demographics: more common in African Americans, who tend to be diagnosed younger.

• IBC is rare but very aggressive (approx. $1\%\text{ to }5\%$ of breast cancers).

Ovarian Cancer

• Typical patient: middle-aged or older woman with vague abdominal bloating/discomfort, early satiety, GI reflux-type symptoms, low-back/pelvic pain, dyspareunia, changes in bowel habits, fatigue.

• Most patients (≈ $75\%$) are diagnosed after spread beyond the ovary, contributing to poor overall survival.

• Five-year survival with distant metastases is $25\%$; if diagnosed at stage I, survival >$90\%$.

• Current screens (e.g., CA-125) lack sufficient specificity for average-risk; transvaginal ultrasound alone performs poorly for early-stage disease.

• Family history look-for: two or more first- or second-degree relatives with ovarian, endometrial, or colon cancer, or a combination of ovarian and breast cancer.

• Women with high-risk family histories should be referred for genetic counseling and testing (e.g., BRCA1/BRCA2, Lynch syndrome).

• Screening can start $10\text{ years}$ before the earliest age of first diagnosis in the family.

Paget’s Disease of the Breast (PDB)

• Older female with a history of a red, scaly rash starting on the nipple and spreading to the areola of one breast.

• Symptoms may include itching, pain, burning; skin lesion may enlarge and crust/ulcerate/bleed.

• Up to half of women have an associated breast mass.

• Rarely occurs in men.

Normal Findings: Anatomy – Breasts

• Puberty starts with breast buds (Tanner stage II) and ends at stage V.

• During puberty, tender and asymmetrical breast buds are common; one breast can be larger (gynecomastia in some boys).

• Tail of Spence is the most common cancer site.

• Simple breast cysts are benign, round to oval; highest prevalence ages $35\text{-}50$.

• Fibroadenomas are the most common solid breast tumors; consist of fibrous tissue; ultrasound preferred; biopsy sometimes needed.

• High estrogen levels promote growth of fibroadenomas; low estrogen (menopause) may shrink them.

• BRCA1/BRCA2 mutations can raise lifetime breast-cancer risk to as high as $72\%$.

• Risk factors for male breast cancer include cryptorchidism, positive family history, and BRCA mutations.

• Diagnostic test for breast cancer or any solid tumor: tissue biopsy.

Cervix and Transformation Zone

• Cervical ectropion: bright-red, bumpy tissue with irregular surface around the os; benign; more friable than surrounding squamous epithelium.

• Ectropions may enlarge with high estrogen states (adolescents, combined hormonal contraception, pregnancy).

• If ectropion is present, sample the transformation zone (TZ) during Pap testing; TZ is where ectropion meets squamous epithelium and is a common site for metaplasia and abnormal cells.

Cervical and Vaginal Mucus

• Mucus varies: scant to thick white, runny white, or clear stringy mucus.

• After menses, discharge is scant; midcycle, large amount of clear mucus (the mucus plug) is normal unless on hormonal contraception (which thickens mucus).

• Mucus can be mixed with blood and appear red to dark-brown during menses.

Uterus

• Uterus includes the corpus and cervix; endometrium consists of glandular epithelium and stroma.

• Fibroids (uterine leiomyoma) can enlarge the uterus; may be asymptomatic or cause menorrhagia, pelvic pain, intermenstrual bleeding.

• Fibroids are usually benign; rare malignant transformation to leiomyosarcoma.

Ovaries

• Ovaries produce estrogen, progesterone, and small amounts of testosterone.

• Polycystic ovary syndrome (PCOS): multiple ovarian cysts with higher estrogen and higher androgens; symptoms include acne, hirsutism, oligomenorrhea, insulin resistance.

• During menopause, ovaries atrophy; a palpable ovary in a postmenopausal woman is abnormal – rule out ovarian cancer; order pelvic/intravaginal ultrasound and refer to a gynecologist.

Benign Variants

• Supernumerary nipples form a V-shaped line on both sides of the chest down the abdomen and are symmetrically distributed.

Menstrual Cycle – Normal Findings

• Based on a 28-day cycle.

• Follicular (proliferative) phase: Days 1–14.

  • FSH from the anterior pituitary stimulates ovarian follicle maturation.

  • Estrogen produced by developing follicles; estrogen is predominant in the first two weeks and stimulates endometrial growth.

• Ovulatory phase: Day 14 (midcycle).

  • LH surge from the anterior pituitary induces ovulation and maturation of the dominant follicle.

  • The follicle migrates to the fimbriae of the fallopian tube; conception may occur.

• Luteal phase: Days 14–28.

  • Progesterone from the corpus luteum predominates and stabilizes the endometrium.

Menstruation

• If not pregnant, estrogen and progesterone fall drastically, triggering menses.

• The drop in hormones stimulates the hypothalamus and the pituitary to initiate a new cycle via FSH.

Menopause

• Menopause: cessation of menses for 12 consecutive months; average age ≈ $51\text{ years}$.

• Perimenopause: ~10 years around the final menstrual period with hormonal fluctuations.

• Premature menopause (primary ovarian insufficiency): cessation of menses before age $40\text{ years}$; vasomotor symptoms common; vaginal dryness, decreased lubrication, libido changes; urinary symptoms may occur if estrogen is not used.

Women’s Health Initiative (WHI) and Hormone Therapy

• Average US menopause age ≈ $51\text{ years}$.

• WHI findings: combined estrogen–progestin therapy increases risks of stroke, heart disease, venous thromboembolism (VTE), breast cancer, and pulmonary embolism.

• USPSTF guidance (general): does not recommend combined estrogen–progestin or unopposed estrogen for chronic disease prevention; applicability to relief of menopausal symptoms may differ.

• Practical guidance: duration of hormone therapy typically <$5\text{ years}$; many experts consider it acceptable for healthy women within <60\text{ years} and within 10 years of menopause, with no contraindications.

• Estrogen-alone therapy can alleviate dyspareunia and vaginal/urethral atrophy; estrogen can worsen or exacerbate systemic lupus erythematosus (SLE) risk.

• For women with a uterus, use both estrogen and progesterone (or progestin) to reduce endometrial cancer risk; unopposed estrogen is used only after hysterectomy.

Fertile Time Period and Ovulation Testing

• Highest pregnancy chance occurs 1–2 days before ovulation; characterized by copious, clear, thin, elastic cervical mucus.

• Cervical mucus method for fertility awareness; ovulation kits (urine LH) can detect LH rise within ~$12\text{ hours}$ after it appears in serum.

• False positives can occur with PCOS, ovarian failure, or menopause.

Conception and Early Pregnancy

• Conception occurs when sperm fertilizes the egg; the zygote travels down the fallopian tube to the uterus and divides to form a blastocyst.

• Implantation occurs in the endometrium; typically takes $3\text{ to }4\text{ days}$ for implantation.

• Placenta fully formed by $18\text{ to }20\text{ weeks}$.

• Hormones: estrogen and progesterone rise; human chorionic gonadotropin (hCG) produced by placenta.

• Pregnancy duration: $280\text{ days}$ or $40\text{ weeks}$.

Laboratory Procedures: Cervical Cytology (Pap Test)

• Liquid-based cytology (e.g., ThinPrep) is used to screen for cervical cancer and is read by computer; higher false-negative rates (historically $20\%\text{ to }45\%$).

• If the cervix bleeds easily during sampling, consider cervicitis.

• Some individuals may have slight spotting after Pap testing.

• Do not perform a Pap test or liquid-based cytology during heavy menses.

• Best time to perform Pap: at least $5\text{ days}$ after menses stops.

• Avoid douching, vaginal products, tampons, or intercourse for 2$–$3\text{ days} before Pap.

2018 Screening Guidelines (Summary)

• USPSTF: no cervical cytology before age $21\text{ years}$; age 21–29 cytology alone; age 30–65 Pap with co-testing (HPV) or Pap every 3 years; up to every $5\text{ years}$ with co-testing if normal.

• ACOG: higher-frequency screening for HIV-positive or DES-exposed individuals, or others with special risk.

Liquid-Based Cervical Cytology (ThinPrep)

• Use a broom-shaped plastic brush inserted into the cervical os; ensure sampling of transformation zone if present.

• Place brush in liquid medium and swish; cover; read by computer; abnormal results reviewed by cytologist/pathologist.

Conventional Pap Test

• Use a wooden spatula to sample ectocervix (ectocervix surface) and brush for endocervix; smear both on a slide; fix with spray.

• Sampling ectocervix first minimizes bleeding.

Screening Women Without a Cervix

• Stop screening if a patient has had a hysterectomy for a benign condition and is not at high risk for cervical cancer.

Bethesda System (Cervical Cytology Reporting)

• A standardized reporting system for cervical cytology.

• Specimen satisfactory if both squamous epithelial cells and endocervical cells are present; absence of endocervical cells occurs in ~$10\%\text{ to }20\%$ of specimens and is common in adolescents and postmenopausal women.

• Considerations when sampling: pelvic radiation or pregnancy should be noted; lubricants or excessive blood can interfere with results.

• ASC-US (Atypical Squamous Cells of Undetermined Significance): mildly abnormal cells with unidentified cause (infection, irritation, or precancer).

• Age-specific guidelines for ASC-US and HPV testing:

  • Age $20\text{-}\text{years}$ or younger: do not perform Pap if younger than 21.

  • Age $21\text{-}\text{24}$: repeat Pap in 12 months preferred; reflex HPV acceptable.

  • Age $25\text{-}\text{29}$: reflex HPV preferred; repeat Pap in 12 months acceptable.

  • Age 30\text{ or older}$: cotesting with high-risk HPV; if HPV positive, colposcopy.

• ASC-H (Atypical Squamous Cells Cannot Exclude HSIL): presence suggests possible precancer; requires colposcopy (age 21\text{ or older}$).</p></li><li><p>AGC (Atypical Glandular Cells): associated with premalignancy or malignancy in 30$11\text{ or }12$; can be given from age$9$to$26$.</p></li><li><p>If first dose before age 15, a two-dose series is required (0, 6–12 months).</p></li><li><p>If first dose at age 15 or older, a three-dose schedule (0, 1–2, 6 months).</p></li><li><p>Schedule interruptions do not require dose repetition; vaccine now recommended for ages$9\text{ to }45$.</p></li></ul><h3 id="8c90effd-c7ce-4f4a-9499-edd45773525d" data-toc-id="8c90effd-c7ce-4f4a-9499-edd45773525d" collapsed="false" seolevelmigrated="true">Colposcopy and Related Procedures</h3><ul><li><p>Colposcopy: specialized microscope to visualize the cervix, obtain biopsies, and access treatment (cryotherapy or laser) as needed.</p></li><li><p>A vaginal speculum is used to expose the cervix.</p></li><li><p>After visualization, acetowhitening is performed with 3–5$21$—even with STI exposure or multiple partners; pelvic exam may be used to check for PID and STI testing.</p></li><li><p>Do not confuse endometrial biopsy with colposcopy.</p></li></ul><h3 id="3d984b19-853d-4f91-bf17-74fcb1b242f4" data-toc-id="3d984b19-853d-4f91-bf17-74fcb1b242f4" collapsed="false" seolevelmigrated="true">Contraception Overview</h3><ul><li><p>Infertility: defined as failure to conceive after$12\text{ months}$of unprotected sex; roughly$50\%$of pregnancies in the US are unplanned.</p></li><li><p>A table of method effectiveness (simplified):</p><ul><li><p>Least effective: fertility awareness, spermicide, male/female condom, withdrawal, sponge.</p></li><li><p>Moderate effectiveness: injectable, pill, patch, ring, diaphragm.</p></li><li><p>Most effective: implant, IUD, vasectomy, tubal/hysterectomy.</p></li></ul></li><li><p>Minors: many states allow consent to contraceptive services without parental consent; some require age thresholds.</p></li><li><p>Rule out pregnancy before initiating contraception; check blood pressure as part of health eval.</p></li><li><p>OC (combined hormonal contraception) basics:</p><ul><li><p>Several types: monophasic, biphasic, triphasic pills; ethinyl estradiol (EE) with various progestins.</p></li><li><p>Drospirenone-containing pills (Yaz, Yasmin, Slynd) have higher DVT and hyperkalemia risk; monitor potassium in patients on ACE inhibitors, ARBs, or potassium-sparing diuretics.</p></li><li><p>Extended-cycle options (Seasonale, Yaz/Desogen variants) reduce frequency of menses; may cause breakthrough bleeding early on.</p></li><li><p>Non-oral forms include the cervical ring (NuvaRing) and transdermal patch (Ortho Evra); higher estrogen exposure with patch can increase VTE risk.</p></li><li><p>BP monitoring: estrogen-containing methods can raise blood pressure; reassess within$4$-$8 weeks of initiation.

• Breastfeeding considerations: progestin-only pill (POP) or other progestin-only methods are preferred during lactation.

Combined Hormonal Contraception – Practical Aspects

• Absolute contraindications include conditions increasing clot risk (thrombophlebitis, thromboembolic disorders, coagulation defects like factor V Leiden), major surgery with immobilization, heavy smoking (>15 cigarettes/day) in women >35, high stroke risk (e.g., CVA, TIA, certain migraines), active liver disease, pregnancy, and certain cancers (estrogen-dependent).

• Relative contraindications include migraines with aura (especially >35$), smoking younger than$35$, uncontrolled hypertension, and other cardiovascular risk factors.</p></li><li><p>Special mnemonics: My CUPLETS (Migraine with aura, CAD/CVA, Undiagnosed bleeding, Pregnant, Liver tumors, Estrogen-dependent tumor, Thrombus/embolus, Smoker) as a quick reference for absolute contraindications.</p></li><li><p>Drospirenone-containing pills: avoid in hyperkalemia, kidney disease, or adrenal insufficiency.</p></li><li><p>Common adverse effect management:</p><ul><li><p>Unscheduled (spotting) bleeding is common in the first weeks; usually improves by the 3rd month.</p></li><li><p>Lower-estrogen-dose pills may have higher breakthrough bleeding; switching to ~$30\mu g$EE formulations may help.</p></li><li><p>If a dose is missed, follow standard guidance for doubling up and using backup contraception as needed; if a dose is missed in the last week, finish current pack and start a new pack immediately.</p></li></ul></li></ul><h3 id="08195cd7-056d-4e38-94f1-7b8951d002bd" data-toc-id="08195cd7-056d-4e38-94f1-7b8951d002bd" collapsed="false" seolevelmigrated="true">Contraception: Special Methods</h3><ul><li><p>Combined Oral Contraceptives (COCs): various regimens; typical-use failure ~$9\%$; include iron-containing last week pills in some brands.</p></li><li><p>Rapid-start strategies: quick-start, day-one start, Sunday start; ensure pregnancy ruled out; backup contraception typically required for the first$7\text{ days}$.</p></li><li><p>Ring (NuvaRing): 3 weeks in, 1 week out; continuous use possible; do not use in women who smoke and are ≥$35$.</p></li><li><p>Patch (Ortho Evra): 3 weeks wear, then 1 week off; higher estrogen exposure; higher VTE risk; adherence considerations.</p></li><li><p>Progestin-only methods (POP, DMPA, etonogestrel implant, LNG IUD) vary in duration and side effects; POPs require strict timing; DMPA (Depo-Provera) lasts ~$3\text{ months} per dose and can cause amenorrhea with long-term use; boxed warning for bone density effects with long-term use (> 2\text{ years} $).</p></li><li><p>Intrauterine devices (IUDs): LNG-releasing (e.g., Mirena) for up to$5\text{ years}$; copper IUD (Paragard) up to$10\text{ years}$; LNG IUD reduces bleeding; copper IUD may cause heavier menses initially; insert only by trained clinician; contraindications include active PID, pregnancy, known STI, uterine/cervical abnormalities, prior ectopic pregnancy, Wilson’s disease (copper IUD).</p></li><li><p>Barrier methods: male/female condoms; diaphragms with spermicide; cervical caps; spermicides increase infection risk with HIV; avoid silicone oil lubricants with silicone-based devices.</p></li><li><p>Emergency contraception: effective if used within$72\text{ hours}$(ulipristal: up to$120\text{ hours}$); LNG pills include Plan B One-Step, My Way, Next Choice; some regimens require taking two doses 12 hours apart; check for pregnancy if period delayed.</p></li><li><p>Cervical hygiene and partner treatment considerations: BV and trichomonas require partner treatment rarely (BV generally not STI-driven); all patients should be counseled on safer sex practices and STI screening where indicated.</p></li></ul><h3 id="5317ee42-a843-498d-8777-c717b0e8a8e3" data-toc-id="5317ee42-a843-498d-8777-c717b0e8a8e3" collapsed="false" seolevelmigrated="true">Pelvic Organ Prolapse</h3><ul><li><p>Prolapse can involve cystocele (bladder), rectocele (rectum), uterine prolapse, enterocele (small bowel), and vaginal vault prolapse.</p></li><li><p>Causes: weakening of pelvic floor muscles and ligaments; may be asymptomatic early.</p></li><li><p>Evaluation: bimanual exam with bearing down to reveal prolapse.</p></li><li><p>Plan: pessary placement or surgical repair (urogynecologist referrals).</p></li><li><p>Management by compartment: cystocele (anterior wall bulging; urinary symptoms); rectocele (posterior bulging; constipation/rectal fullness); uterine prolapse (cervix descends; may require surgery or pessary); enterocele (small bowel herniation).</p></li></ul><h3 id="e245f24c-3e8f-42bb-888b-57637570c1b2" data-toc-id="e245f24c-3e8f-42bb-888b-57637570c1b2" collapsed="false" seolevelmigrated="true">Polycystic Ovary Syndrome (PCOS)</h3><ul><li><p>Hormonal disorder with anovulation/oligo-ovulation, infertility, hyperestrogenism, hyperandrogenism, and insulin resistance.</p></li><li><p>Associated risks: type 2 diabetes, dyslipidemia, metabolic syndrome, endometrial hyperplasia, obesity, depression, sleep apnea.</p></li><li><p>Classic presentation: overweight adolescent/young woman with hirsutism (≈70$35\text{ and }40\text{ years}$for BRCA1/BRCA2 carriers after childbearing; reduces ovarian cancer risk significantly.</p></li><li><p>Pelvic organ prolapse and related conditions require pelvic floor rehabilitation and possible surgical repair depending on severity.</p></li></ul><h3 id="df95941f-b8e0-4c3c-8bc7-9045a54a35b3" data-toc-id="df95941f-b8e0-4c3c-8bc7-9045a54a35b3" collapsed="false" seolevelmigrated="true">Quick Reference: Key Numerical Values, Formulas, and Concepts</h3><ul><li><p>Lifetime risk thresholds and surveillance:</p><ul><li><p>BRCA-associated cancer risk contributions:$6\%\ (breast)$,$20\%\ (ovarian)$.</p></li><li><p>Screening initiation: start ten years before youngest affected relative's diagnosis age.</p></li></ul></li><li><p>Menstrual cycle timing:</p><ul><li><p>Follicular phase: Days$1-14$; Ovulation around day$14$; Luteal phase: Days$14-28$.</p></li></ul></li><li><p>Pregnancy timing:</p><ul><li><p>Implantation:$3$-$4\text{ days}$after fertilization.</p></li><li><p>Placenta formation complete by$18$-$20\text{ weeks}$.</p></li><li><p>Gestation duration:$280\text{ days}$or$40\text{ weeks}.