20. Gynecology




Ninety-five percent of ovarian cancers arise from the epithelial portion and only 5% are germ-cell tumors. As opposed to this, 90% of testicular cancers arise from germ cells.


The reason germ-cell tumors are less common in females is because a female germ-cell system only produces one egg per month (approximately 300-400 in a female’s life), whereas a male germ-cell system produces about 525 billion sperm cells over a lifetime. Less active cell multiplication means smaller chance of abnormal cell division.



20.1 Normal Menstrual Cycle



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Day 1 of menstrual cycle is the first day of menses.


There are two phases, each lasting approximately 14 days in a 28-day cycle:




  • Follicular phase:




    • Follicle-stimulating hormone (FSH) stimulates the growth of ovarian follicles and secretion of estrogen by follicles.



    • A luteinizing hormone (LH) and FSH surge leads to release of a mature ovum from the ovarian follicle (ovulation), ending the follicular phase.



  • Luteal phase:




    • After ovulation, the remains of the follicle develop into the corpus luteum that produces estrogen and progesterone, which prepare uterine lining for implantation.



      1 Anovulatory cycles result in unopposed estrogen secretion, as there is no formation of corpus luteum that secretes progesterone.




    • If fertilization does not occur, the corpus luteum withers away, and with decreasing progesterone, menstruation results (end of the cycle).



    • If fertilization occurs, the embryo starts making β-hCG, which signals the corpus luteum to continue producing progesterone and estrogen (which maintain the uterine lining).



20.2 Menstrual Pathologies






























Terminology


Description


Secondary amenorrhea


No menses for:




  • >3 months in a previously regular menstrual cycle, or



  • > 6 months in previously irregular menstrual cycle


Oligomenorrhea


Prolonged menstrual cycles > 35 days in length, or < 9 menstrual cycles per year


Menorrhagia


Heavy and prolonged menstrual bleeding


Hypomenorrhea


Light menstrual bleeding or spotting


Metrorrhagia


Bleeding between menstrual periods


Menometrorrhagia


Irregular bleeding that is prolonged or excessive



20.3 Abnormal Uterine Bleeding


Etiology:


















Structural causes


Functional causes




  • Polyp (uterine), Pregnancy-related



  • Adenomyosis



  • Leiomyoma



  • Malignancy and hyperplasia




  • Coagulopathy



  • Ovulatory dysfunction



  • Not yet classified



  • Endometrial


Ovulation is usually normal. Thus, presentation is usually menorrhagia (i.e., cyclical heavy bleeding)


MCC of functional bleeding is ovulatory dysfunction leading to anovulatory cycles, which presents as irregular and noncyclical bleeding.



MRS

PALM CONE that bleeds


Management:




  • In reproductive age patients, the first step is to rule out pregnancy.



  • Control bleeding and treat anemia if present and look for bleeding disorders (e.g., von Willebrand disease).



  • Oral contraceptive pills (OCPs) with estrogen and progesterone are first-choice agents. (In ovulatory dysfunction, it is important to decrease the risk of endometrial hyperplasia and cancer, by counteracting the effect of unopposed estrogen.)



    2 Other choices include oral or injectable progesterone and levonorgestrel containing hormonal IUD. These also decrease risk of endometrial hyperplasia and cancer.




  • If patient does not want hormonal treatment:




    • Mild symptoms—nonsteroidal anti-inflammatory drugs (NSAIDs) or tranexamic acid (anti-fibrinolytic agent).



    • Significant bleeding—endometrial ablation, or in women who do not desire further pregnancy, hysterectomy.


Management of acute severe bleeding




  • Address hemodynamics first—IV fluid resuscitation and transfusion as needed. Treat underlying blood disorder if present (e.g., give von Willebrand factor concentrate for von Willebrand disease).



  • For hemodynamically unstable patient, NSIM is intrauterine tamponade (balloon or gauze packing), then uterine curettage. For persistent bleeding, start IV estrogen. Emergency hysterectomy might be needed in refractory cases.



  • For hemodynamically stable patient, NSIM is high-dose oral estrogen.



20.3.1 Secondary Amenorrhea


Criteria: No menses for > 3 months in a previously regular menstrual cycle, or > 6 months in previously irregular menstrual cycle.


Diagnostic evaluation:


MCC is pregnancy, so first do β-hCG testing. If pregnancy is ruled out, look at the following algorithm for workup.



3 The following algorithm can also be used for workup of hypo/oligomenorrhea with some minor changes.








aIf there is evidence of hyperandrogenism (e.g., hirsutism, acne), also check serum testosterone level. Think of polycystic ovary syndrome (PCOS).


bBoth hypo- and hyperthyroidism can cause amenorrhea. In hypothyroidism, thyrotropin-releasing hormone stimulates both thyroid-stimulating hormone (TSH)



4 Remember to check TSH in any patient presenting with irregular menses.

and prolactin secretion. Prolactin inhibits gonadotropin-releasing hormone (GnRH; low FSH and LH).


cThis results in hypergonadotropic hypogonadism. Look for symptoms of hot-flashes and/or atrophic vaginitis.


dCauses of hypogonadotropic hypogonadism are:


• Bulimia nervosa


• Significant chronic illness


Excessive exercise or weight loss


• Starvation


• If there is no obvious etiology, NSIDx is MRI to look for pituitary disorders. Sheehan’s syndrome (postpartum pituitary necrosis) is a potential cause, if there is a history of pregnancy-related hemorrhage.


eThe idea behind progestin challenge is that a woman with sufficient estrogen level will have withdrawal bleeding after a dose of progesterone, indicating that amenorrhea is likely due to progesterone deficiency, e.g., chronic anovulation in conditions such as PCOS.



In a nutshell





































Condition


Estrogen


FSH


LH


Hypergonadotropic hypogonadism (menopause or premature ovarian failure) a


Low




Hypogonadotropic hypogonadism = pituitary dysfunction


Low


Low


Low


PCOS


Normal or slightly highb


Usually falls within normal limits—as estradiol is normal.


c


aPremature ovarian failure can be due to chemotherapy/radiation, autoimmune conditions, Turner’s syndrome, etc.


bPCOS patients are typically obese and have a higher testosterone level. Peripheral conversion of testosterone into estrogen in the adipose tissues maintains the estrogen level.


cIn PCOS, LH/FSH ratio is typically > 1.



20.4 Polycystic Ovary Syndrome (PCOS)


Background: Exact etiology is unknown. Main problem is abnormal steroidogenesis in ovaries with increased androgen production. It is the MCC of infertility in women.


Presentation:


Typical features



5 Usually presents in puberty and gradually worsens.

:




  • Hyperandrogenism (hirsutism, acne, androgenic alopecia).



  • Irregular menstrual cycle, amenorrhea, and anovulation.



  • Due to issues with follicular development and regression, there are multiple immature follicles in ovaries. These look like cysts in ultrasound (polycystic-looking ovaries).



  • Insulin resistance, acanthosis nigricans, weight gain, obesity, and type 2 diabetes. Diagnostic evaluation:


Pelvic US will show ovaries that look like they have multiple cysts in them.




  • PCOS is a diagnosis of exclusion: rule out conditions that present similarly to PCOS (i.e., other causes of late-onset virilization and hyperandrogenism). Check 17-OH progesterone level, TSH, prolactin, IGF-1, cortisol, and testosterone levels.



    6 Remember, not all women with US findings of multicystic ovaries have PCOS. Other causes of hyperandrogenism can also lead to similar picture in ultrasound.














































Differential dx of PCOS


Key features


Laboratory findings


Nonclassic congenital adrenal hyperplasia, due to mild 21-hydroxylase deficiency with some 21-hydroxylase activity present




  • May present in late childhood to early adulthood, unlike severe ones which present at birth



  • May also have polycystic ovaries and hypo/amenorrhea




  • Elevated 17-OH- progesterone level


Ovarian hyperthecosis (idiopathic hyperplastic increase of luteinized thecal cells that overproduce androgen)a




  • Primarily seen in postmenopausal women




  • High testosterone



  • Normal DHEAb


Ovarian or adrenal virilizing tumors




  • These are typically rapid in onset



  • Pelvic and adrenal US may reveal the tumor.




  • Markedly elevated androgens (testosterone and/or DHEAc)



  • Low LH


Cushing’s syndrome (they may have hirsutism and oligo/amenorrhea)




  • Centripetal obesity



  • Diabetes



  • Other features of corticosteroid excess




  • High cortisol


Hyperprolactinemia




  • Hypogonadism and oligo/ amenorrhea



  • Galactorrhea




  • High prolactin


Acromegaly




  • Increased bone growth




  • Increased insulin-like growth factor-1


aThis is thought to be due to genetic mutation. Similar in pathophysiology, luteoma (which can occur with normal pregnancy) and hyperreactio luteinalis (associated with abnormally high β-hCG, which occurs with multiple gestation, molar pregnancy, ovulation induction, etc.) can result in transient hyperandrogenism.


bNormal DHEA with elevated testosterone suggests extra-adrenal sources (typically ovaries). Elevated DHEA suggests adrenal virilizing tumors.


Abbreviations: DHEA, dehydroepiandrosterone; LH, luteinizing hormone.








Source: BruceBlaus, CC BY-SA 4.0, via Wikimedia Commons.


Management of PCOS:




  • First step is weight loss (this not only decreases insulin resistance and risk of diabetes, but may also restore ovulation).



  • Second step depends upon the patient’s goal.
























Women who do not desire pregnancy


Women who wish to get pregnant




  • Combination OCP (this will decrease risk of endometrial hyperplasia/cancer,a menstrual abnormalities, and decrease androgenic symptoms).



  • For persistent hyperandrogenic symptoms, second line is spironolactone.


Induce ovulation:




  • Clomiphene, or



  • Letrozoleb (preferred in women with BMI of > 30)


Metformin is used as an adjunctive treatment in patients with obesity, diabetes mellitus (DM), or impaired fasting glucose.c


aRemember that chronic anovulation is associated with increased risk of endometrial hyperplasia and cancer due to unopposed estrogen effect.


bLetrozole is an aromatase inhibitor that decreases estrogen production and thus removes negative feedback effect on FSH.


cStudies have not shown protective effect of metformin on endometrium.



20.5 Contraception


FYI: Given in order of somewhat effective to highly effective (e.g., failure rate of spermicides is ≈ 25-33%; failure rate of vasectomy is ≈ 0.15%).



















































Method


Considerations


Spermicide use




  • Can cause irritation of genitalia, and allergic reaction



  • Inexpensive



  • May INCREASE risk of STD transmission due to mucosal irritation



  • High failure rate


Calendar method (avoid intercourse near predicted ovulation days)




  • Requires couple to predict ovulation



  • High failure rate


Withdrawal method (ejaculate outside the vagina)




  • High failure rate


Female or male condom




  • Best contraception that protects against STDs (including HIV)


Diaphragm (barrier method)— used with spermicide




  • Does not protect against HIV



  • Potential for toxic shock syndrome (TSS) if left in place too long



  • Not commonly used nowadays


Vaginal ring (hormonal method)




  • Remains in place for 3 weeks and in the fourth week of menstrual cycle it can be removed (ringfree week). Reinsert after the end of the fourth week.



  • Does not need to be removed for intercourse



  • Fertility returns in 1 month after discontinuation



  • No STD protection


Oral contraceptive pill (OCP)




  • Requires daily ingestion



  • Reduces incidence of ovarian cancer, endometrial cancer, ectopic pregnancy, pelvic inflammatory disease (PID),a etc.



  • Increased risk of benign hepatic tumors, gallbladder disease, hypercoagulability, cervical cancer, hypertension



  • Increased triglycerides



  • No STD protection



  • Does not cause weight gain (the dose is typically low)


Hormonal transdermal patch (combined estrogen/ progesterone)




  • Apply weekly for 3 weeks; the fourth week is patch-free week.



  • Possible skin irritation



  • If patch detaches from skin for > 24 hours, it needs to be replaced with a new one.



  • Same advantages and disadvantages as OCPs (e.g., no STD protection, higher risk of venous thromboembolism)


Hormonal progesterone injection—depot medroxyprogesterone acetate (DMPA)




  • High efficacy and requires injection only every 3 months



  • If late by > 2 weeks, do pregnancy test before giving q3 monthly injection



  • Reduction in risk of endometrial cancer, PID,a and amount of menstrual bleeding



  • May have irregular bleeding or hypo/amenorrhea, weight gain, depression.



  • There is a delay of return to menstruation once injections are stopped and return to fertility may take longer (≈1-1.5 year)


Intrauterine device (IUD) Two types—copper IUD and hormonal IUD (hormone is levonorgestrel—a progesterone agonist)




  • This is the most effective nonsurgical contraception



  • Requires physician to place and remove



  • Rapidly reversible and cost-effective



  • Hormonal IUD lasts 5 years; copper IUD ≈ 10 years



  • Hormonal IUD may decrease menses (useful in menorrhagia and dysmenorrhea), and decreases risk of PIDa



  • There is no weight gain with levonorgestrel-containing IUD



  • Copper-containing IUD may cause heavy/painful menses (which often improves after some time)



  • Copper IUD may be used as emergency contraception



  • Higher risk of ectopic pregnancy if woman becomes pregnant with IUD in place



  • Not to be placed within 3 months of dx of STD



  • Previous hx of STD or ectopic pregnancy IS NOT a contraindication for IUD


Female sterilization (tubal ligation)




  • Permanent



  • High efficacy, however if pregnancy results, there is increased risk of ectopic implantation.



  • Risks associated with surgery: infection, hemorrhage, anesthesia complications, etc.



  • Tubal ligation with complete salpingectomy may decrease risk of ovarian cancer


Male sterilization (vasectomy)




  • Permanent



  • High efficacy



  • Safer and less costly than female sterilization



  • Can be performed in the outpatient setting


aPossibly due to thick impenetrable mucus.



20.5.1 Short Note on Oral Contraceptive Pills (OCP)


Formulary: A 28-pill OCP pack has 21 hormone pills (known as active pills). The additional seven pills are placebo pills (containing sugar or iron) to help the user stay in the habit of taking a pill every day.


Mechanism of action: Combination of estrogen and progesterone prevents mid-cycle LH surge and follicular maturation. Progesterone also works by making endometrium less suitable for implantation, and by making cervical mucus thick (this might be the reason for the decreased risk of PID).


Absolute contraindications to OCP:




  • History or risks of venous thromboembolism.



  • Tobacco use (more than half a pack per day) and age ≥ 35.



  • Liver disease (cirrhosis, liver cancer, etc.).



  • Clinical history of atherosclerotic cardiovascular disease (ASCVD; e.g., coronary artery disease), or high ASCVD risk (e.g., uncontrolled diabetes).



  • Hypertension (systolic of ≥ 160 mmHg or diastolic of ≥ 100 mmHg).



  • Migraine with aura.



  • Migraine without aura in > 35 years of age or with tobacco abuse.



  • Breast cancer.



  • Systemic lupus erythematosus.



  • Complicated valvular heart disease.



Clinical Case Scenarios

1. Patient calls with an issue of two missed active pills. What is the NSIM?


Emergency contraception






















Most effective


Very effective


Effective


Copper IUD (not hormonal IUD)


Ulipristal (antiprogestin)


Levonorgestrel


Needs to be inserted within 5 days after unprotected sex




  • Can be used up to 5 days after unprotected sex



  • Requires prescription




  • Can be used up to 3 days after unprotected sex



  • Available over the counter



20.6 Differential Diagnosis of Dysmenorrhea

7 Dysmenorrhea refers to uterine pain that occurs with the menstrual cycle.

and Pelvic Pain












































Condition


Features


Management


Primary dysmenorrhea (most common) Pathophysiology: Due to prolonged uterine contractions likely mediated by prostaglandins


Presentation: recurrent crampy suprapubic pain that occurs with or just before the menses




  • Normal pelvic exam




  • First step is to rule out pregnancy and infection.


Rx: Exercise and heat application is 1st line. If not responding, 2nd line is NSAIDs like ibuprofen or hormonal therapy (combination OCPs or progestin-only pills). If 1st line NSAIDs fail, 2nd line NSAIDs is mefenamic acid (a specific type of NSAIDs for menstrual pain). For patients who desire contraception, use combination OCPs or progestin-only pills.


Secondary dysmenorrhea usually presents in adulthood


Endometriosis


Pathophysiology: presence of endometrial stroma and glands outside the uterus


Presentation depends on location of endometriosis:




  • Pelvic: Dysmenorrhea, dyspareunia



  • Bladder: Urinary frequency, urgency, dysuria



  • Others: Constipation, hematochezia, infertility, etc.


Typically, pain is cyclical with/ without menses.


Pelvic exam: May reveal


fixed retroverted uterus (endometrial cells “glue” the uterus to posterior pelvic structures), tender nodular masses along uterosacral ligaments or in cul-de-sac, etc.


Abdominal/transvaginal US may show ectopic endometrial tissue.


Rx:




  • First line is NSAIDs + hormonal contraception.



  • Laparoscopy (diagnostic and therapeutic) is indicated for any of the following:




    • Severe symptoms



    • Patients who have failed medical therapy or have contraindications



    • Hx of infertility



  • Second-line agents are GnRH agonist.a Third-line treatment is aromatase inhibitor (before giving second- or thirdline agents, diagnostic laparoscopy is recommended.)



  • Definite treatment is hysterectomy with oophorectomy.




  • Ovarian endometriosis = endometriomas




    • It is the MC site of endometriosis.


For symptomatic or enlarging endometriomas, first SIM is laparoscopic management (it is important to rule out ovarian malignancy).


Leiomyomas


(uterine fibroids)


Pathology: Benign tumor arising from smooth muscles in uterus.


It is the MC pelvic tumor in women. It is more common in African-American women.


Presentation: Can be asymptomatic and often an incidental finding on US.


Symptomatic patients may have any of the following:




  • Cyclical pelvic pain



  • Heavy/or prolonged menstrual bleeding



  • Dysmenorrhea



  • Infertility



  • Fibroids can push on the bladder or colon and cause symptoms (e.g., frequent urination, constipation).



  • Fibroids can also protrude through vagina.



  • Acute pain can occur due to degeneration or torsion.


Pelvic exam: May reveal asymmetrically enlarged uterus with an irregular surface.


NSIDx: is pelvic ultrasound.


For asymptomatic patients, just follow up.


For most patients with symptomatic fibroids, treatment of choice is surgery.




  • For patients who wish to preserve fertility, consider myomectomy (abdominal approach for subserosal or intramural, and hysteroscopic approach for submucosal). For patients who do not desire to preserve fertility, consider hysterectomy.



  • In severe cases, GnRH agonist can be used to reduce the bulk of disease prior to surgery.



  • Patients who have symptoms due to excessive/painful bleeding and do not want to undergo surgery, consider hormonal IUD.


Adenomyosis


Pathology: Endometrial glands within myometrium


Presentation: Painful, heavy, prolonged menses, and chronic pelvic pain.


Pelvic exam: Symmetrically enlarged tender uterus on pelvic exam.


NSIDx: Transvaginal US reveals symmetrically enlarged uterus; cystic areas can be seen within the myometrium.


Rx: Hysterectomy is curative and provides a definitive dx. Because of diffuse involvement, myomectomy is usually not feasible.


Pelvic inflammatory disease


(can cause secondary dysmenorrhea)


Presentation: Fever, nausea, abnormal vaginal discharge, dyspareunia, etc. Pelvic exam: Cervical motion tenderness, uterine/adnexal tenderness


NSIDx: Cervical specimens for microscopy, nucleic acid amplification tests (NAATs) for C. trachomatis and gonorrhoea (+/-Mycoplasma genitalium). Do not forget pregnancy test and screening for other STDs (HIV, HBV, HCV).


Rx: Antibiotics (see PID section, later in this chapter for further info)


aGnRH agonists are leuprorelin, nafarelin, buserelin (+ relin), etc. Continuous stimulation by GnRH agonist paradoxically results in downregulation of gonadotropin secretion.


Abbreviations: HIV, human immunodeficiency virus; HBV, hepatitis B virus; HCV, hepatitis C virus; STDs, sexually transmitted diseases.



20.7 Premenstrual Syndrome (PMS) and Premenstrual Dysmorphic Disorder (PMDD)




Workup: Ask patient to keep a menstrual diary to record symptoms; the symptoms should occur in the second half of menstrual cycle, impair daily functioning, and improve after menses.


Management:





20.8 Menopause


Definition: Expected cessation of menstrual cycle in old age (ovarian senescence); usual age of onset is > 45 years. (!)


Presentation



8 Obese women usually have milder symptoms, as fat tissue aromatase converts androgen into estrogen.

:




  • Early signs may include menstrual irregularities and anovulatory cycles (menopausal transition).



  • Hot flashes, irritability.



  • Pain during intercourse due to atrophy or dryness of the vagina and cervix.



  • Increased frequency of urination/dysuria due to atrophic urethritis.


Workup: It is a clinical diagnosis, but can be confirmed by elevated FSH and low estrogen level.


Treatment: Hormone replacement therapy (HRT) for short-term management of moderate to severe menopausal symptoms (most importantly hot flashes).




  • Combination estrogen/progesterone for patients with uterus and estrogen only for patients without uterus (see the table below).



  • Topical lubricants and/or topical estrogen for atrophic vaginitis.


Dec 11, 2021 | Posted by in GYNECOLOGY | Comments Off on 20. Gynecology
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