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Sexual & Reproductive Health 3. Treatment a. Excessive exercise or low BMI i. Decrease exercise and encourage weight gain. ii. Combined hormonal contraceptives iii. Estrogen therapy (a) Conjugated estrogens 0.625 to 1.25 mg orally daily on cycle days 1–25 (b) Transder...

Sexual & Reproductive Health 3. Treatment a. Excessive exercise or low BMI i. Decrease exercise and encourage weight gain. ii. Combined hormonal contraceptives iii. Estrogen therapy (a) Conjugated estrogens 0.625 to 1.25 mg orally daily on cycle days 1–25 (b) Transdermal ethinyl estradiol 50 mcg/day patch b. Hyperprolactinemia i. Bromocriptine 2.5 mg orally daily ii. Cabergoline 0.25 mg orally twice weekly; then increase as needed. c. PCOS (see Endocrine and Metabolic Disorders chapter) d. Unknown primary i. Combined hormonal contraceptives ii. Estrogen therapy (a) Conjugated estrogens 0.625 to 1.25 mg orally daily on cycle days 1–25 (b) Transdermal ethinyl estradiol 50 mcg/day patch e. Unknown secondary i. Progestins (a) Micronized progesterone 400 mg orally daily for 10 sequential days to induce menses (b) Medroxyprogesterone acetate 5 to 10 mg orally daily on days 14–25 to induce menses ii. Combined hormonal contraceptives B. Abnormal Uterine Bleeding 1. Definition: “Bleeding from the uterine corpus that is abnormal in regularity, volume, frequency or duration in the absence of pregnancy.” (ACOG Committee Opinion No. 557 April 2013) 2. Causes a. Structural: “PALM” i. Polyp ii. Adenomyosis iii. Leiomyoma iv. Malignancy and hyperplasia b. Nonstructural: “COEIN” i. Coagulopathy ii. Ovulatory dysfunction iii. Endometrial iv. Iatrogenic v. Not yet classified 3. Assessment a. Initial laboratory testing i. Complete blood cell count ii. Blood type and cross-match iii. Pregnancy test b. Check for disorders of hemostasis i. PTT, PT, aPTT ii. Fibrinogen iii. Markers for von Willebrand disease c. Other laboratory tests i. Thyroid-stimulating hormone ii. Iron concentrations ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-602 Sexual & Reproductive Health iii. Liver function tests iv. Chlamydia trachomatis 4. Treatment: Goal is to control current episode of heavy bleeding and reduce menstrual loss in subsequent cycles. a. Acute i. Hormonal therapy: First line (a) Progestins: Medroxyprogesterone acetate 20 mg orally three times daily for 7 days (for acute bleeding) (b) Estrogens: Intravenous conjugated equine estrogens (c) Combined hormonal contraceptives: Best if at least 35 mcg of ethinyl estradiol and monophasic; Estradiol valerate and dienogest (Natazia) has approved indication for heavy menstrual bleeding. ii. Tranexamic acid iii. Desmopressin (use with caution; may help for those with von Willebrand disease) iv. Surgery (a) Hysterectomy (b) Endometrial ablation (not recommended as primary therapy) b. Chronic i. Hormonal therapy: First line (a) Progestins (1) Medroxyprogesterone acetate 5–10 mg orally for 5–10 days starting on day 16 or day 21 of a 28-day cycle (2) Levonorgestrel IUD (b) Combined hormonal contraceptives: Low dose may be option. ii. Surgery (a) Hysterectomy (b) Endometrial ablation (not recommended as primary therapy) C. Dysmenorrhea 1. Definition: Painful menses, usually cramping right before or during menses 2. Causes a. Primary: Caused by menstrual period, mediated by prostaglandins b. Secondary: Caused by disorder in reproductive system (endometriosis, fibroids, adenomyosis), usually starts later in life. 3. Treatment a. NSAIDs: Begin 1–2 days before menses b. Hormonal contraceptives: Combined hormonal contraceptives or levonorgestrel IUD c. Nonpharmacologic approaches (exercise, heat therapy, self-acupressure, acupuncture) D. Endometriosis 1. Definition: Chronic disorder that may result in chronic pain and infertility, endometrial tissue found outside the uterus 2. Treatment a. Hormonal contraceptives i. Combined hormonal contraceptives (not FDA-approved use; effective for dyspareunia, dysmenorrhea, and non-menstrual pain) ii. Depot medroxyprogesterone acetate (subcutaneous formulation, FDA-approved use) iii. Levonorgestrel IUD (not FDA-approved use) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-603 Sexual & Reproductive Health b. Gonadotropin-releasing hormone (GnRH) agonists: Goserelin, leuprolide, nafarelin, triptorelin; recommended as second line because of adverse effect profile i. Consider adverse effects such as osteopenia, hot flashes, vaginal dryness. ii. Recommend calcium 1000 mg orally daily while taking GnRH agonist. iii. May use add-back therapy with norethindrone with or without low-dose conjugated estrogen; transdermal patch with estradiol and medroxyprogesterone acetate may also be used if norethindrone is not well tolerated. iv. See GnRH analog drug information in the Infertility section that follows. c. GnRH antagonists: Elagolix (Orilissa) - Approved for the treatment of moderate to severe pain associated with endometriosis and endometriosis with dyspareunia (N Engl J Med 2017;377:2840); recommended as second line i. Endometriosis dose - 150 mg orally once daily, maximum use 24 months ii. Endometriosis with dyspareunia - 200 mg orally twice daily, maximum use 6 months iii. For moderate hepatic impairment, the dose is 150 mg orally once daily for a maximum of 6 months. iv. Adverse effects: Bone loss, mood changes, elevated liver function enzymes v. Contraindications: Pregnancy, severe osteoporosis, severe hepatic impairment, use of strong organic anion transporting polypeptide 1B1 inhibitors; may decrease effect of estrogencontaining contraceptives (best to use non-hormonal method of contraception during treatment as well as for 7 days after treatment with elagolix) d. Danazol i. Androgenic agent that should be reserved for those without access to other treatment options. ii. Adverse effects: Acne, hirsutism, myalgias e. Aromatase inhibitors: Anastrozole or letrozole, need hormonal contraceptive in addition to minimize risk of ovarian stimulation; reserve for refractory treatment. f. NSAIDs i. Used to help decrease pain ii. Ibuprofen and naproxen g. Surgery E. PCOS (see Chapter, “Endocrine and Metabolic Disorders”) XIV. INFERTILITY A. Background 1. Using no birth control method, women have an 85% chance of pregnancy over 1 year. 2. About 20% of women have their first baby after age 35. 3. Probability of having a baby decreases 3%–5% every year after age 30; faster after age 40. 4. Miscarriages: 12%–15% for those in their 20s, 50% after age 40 B. Things That Can Increase Fertility 1. Diet a. Protein, fruits, and vegetables b. Men need zinc. 2. Exercise, although too much may stop ovulation. 3. Fertility improves with BMI of 20–25 kg/m2 or within 15% of ideal body weight; fertility decreased in those less than 95% of ideal body weight or in those greater than 125% of ideal body weight. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-604 Sexual & Reproductive Health C. Definition 1. Couples who have had unprotected intercourse for 1 year who have not conceived 2. Couples in which the woman is 35 years or older, the couple is having unprotected intercourse, and the couple has not conceived within 6 months D. Risk Factors 1. Age older than 35 years 2. Tobacco use 3. Alcohol use 4. Caffeine use (more than 500 mg/day) 5. Vitamin D deficiency 6. Excessive exercise 7. BMI less than 19 kg/m 2 or more than 25 kg/m 2 for women E. Causes of Infertility 1. Male factor a. Endocrine: Spermatogenesis, hypogonadism b. Anatomic: Blockage, abnormal anatomy c. Sexual dysfunction: Ejaculation or erection difficulties d. Often treated with sperm extraction and assisted reproductive technologies 2. Female factor a. Ovulatory i. WHO group I: Hypogonadotropic hypogonadal anovulation (a) About 5%–10% of anovulatory women (b) Low estrogen, low FSH ii. WHO group II: Eugonadotropic anovulation (normogonadotropic normoestrogenic anovulation) (a) About 75%–85% of anovulatory women (b) Normal FSH concentrations (c) Women with PCOS generally fall into this classification. iii. WHO group III: Hypergonadotropic anovulation (a) About 10%–20% of anovulatory women (b) Elevated FSH concentrations (c) Premature ovarian failure or advanced age fall into this classification. iv. Hyperprolactinemic anovulation (a) About 5%–10% of anovulatory women (b) May have hyperprolactinemia. (c) Laboratory values may appear similar to those in WHO group I. b. Cervical i. Abnormality ii. Blockage iii. Thickened cervical mucus c. Pelvic i. Fibroids ii. Endometriosis iii. Fallopian tube damage or blockage iv. Uterine abnormality v. Pelvic adhesions ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-605 Sexual & Reproductive Health F. Medical Conditions in Women 1. PCOS 2. Endometriosis 3. Pelvic inflammatory disease 4. Uterine fibroids 5. Idiopathic G. Fertility Agents 1. Clomiphene citrate a. Used to stimulate or induce ovulation (used off-label to increase sperm production in men) b. Administered for 5 days starting on days 2, 3, 4, or 5 of cycle c. Taken by mouth usually 50–150 mg/day d. First-line agent, often not effective in WHO group 1 or 3 ovulation disorders e. Selective estrogen receptor modulator that works by blocking estrogen receptors; body perceives hypoestrogenic state and increases the release of GnRH, which increases concentrations of FSH and LH. f. Adverse effects: Hot flashes, abdominal and breast tenderness, mood swings, visual alterations 2. Aromatase inhibitors (off-label use): letrozole, anastrozole a. Increase GnRH and gonadotropins, used in anovulatory WHO group 2 patients b. Help induce ovulation with less risk of multiple follicles stimulated (less risk of multiple births). c. Adverse effects: Headache, GI complaints, joint pain, bone pain, edema, sweating, and flushing 3. Human menopausal gonadotropin (hMG) a. Class known as menotropins, both FSH and LH b. Derived from the urine of postmenopausal women c. Given on day 2 or 3 of cycle and continued for 7–10 days, or as determined by estradiol concentrations and ultrasound monitoring of follicle development. d. Regimens may vary for in vitro protocols. e. Adverse effects: Flu-like symptoms, muscle aches, malaise, headaches, dizziness, pain at site 4. Follicle-stimulating hormone (FSH) a. Naturally occurring (urine source): Bravelle urofollitropin b. Recombinant: follitropin alpha, follitropin beta c. Injection form d. Highly purified e. Helps stimulate development of follicle in ovary; given in the first half of the cycle. f. Adverse effects: Mood swings, depression, breast tenderness and swelling, pain at site 5. Human chorionic gonadotropin (hCG) a. Recombinant: Ovidrel injection subcutaneously b.  Naturally occurring: Derived from urine of pregnant women, Pregnyl or Novarel, injection intramuscularly c. Similar to LH. d. Helps stimulate release of egg; given 36 hours before insemination or harvest. e. Adverse effects: Irritation at site of injection, edema, headache, mood changes, thromboembolic disorder, allergic reactions 6. GnRH analogs a. Used to prevent LH surge that occurs right before ovulation, which helps with timing of ovulation. b. Helps optimize the effectiveness of hMG or FSH. c. Administered by nasal spray, injection, or capsule d. Also used to treat endometriosis. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-606 Sexual & Reproductive Health e. Induces “menopause” state; may cause osteoporosis in women who use agents for long periods; not usually the case in infertility treatment, but more so for endometriosis. f. Agonists versus antagonists i. GnRH agonists (a) Leuprolide, nafarelin (b) Adverse effects: Hot flashes, headache, mood swings, insomnia, vaginal dryness, decreased breast size, bone loss ii. GnRH antagonists (a) Ganirelix and cetrorelix (b) More recently investigated for infertility protocols versus traditional use of GnRH agonists. (c) Said to have fewer complications. (d) Faster onset of action than agonists 7. Metformin a. Sometimes used in conjunction with clomiphene to help ovulation in women with PCOS. b. Increases insulin sensitivity and decreases hyperinsulinemia, thus reducing circulating androgens. c. Weight loss may also occur, leading to better outcomes for ovulation. H. Other Fertility Agents 1. Progesterone: Used for luteal phase support or patients with frequent miscarriages a. Capsules (micronized): Orally, vaginally b. Injectables c. Vaginal suppositories 2. Bromocriptine: Decreases prolactin concentrations; prolactin lowers progesterone concentrations, may prevent ovulation. 3. Sildenafil: Aids in increasing the thickness of uterus lining (off-label use). 4. Guaifenesin: May help thin the cervical mucus to aid in conception (off-label use). 5. Aspirin: Can be used before fertility procedures for uterine blood flow and decreased risk of ovarian hyperstimulation syndrome. I. Complications: Ovarian Hyperstimulation Syndrome 1. Etiology a. Life-threatening complication of assisted conception b. Occurs in less than 4% of cycles for ovulation induction. c. About 1%–10% for in vitro fertilization d. Usually occurs in postovulatory stage. 2. Pathophysiology a. Ovary enlargement b. Capillary permeability increase c. Protein-rich fluid escaping from the intravascular space to the extravascular space d. Patient may start to feel bloated; shortness of breath may occur; lethargy, nausea, vomiting, and diarrhea. 3. Clinical signs a. Rapid weight gain b. Ascites c. Pleural and pericardial effusions d. Oliguria or anuria e. Hemoconcentration f. Leukocytosis g. Hypovolemia, hyponatremia, hyperkalemia ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-607 Sexual & Reproductive Health h. Adult respiratory distress syndrome i. Hypercoagulability j. Multiple organ failure 4. Risk factors a. Young age b. Low body weight c. High estradiol concentrations or rapidly increasing d. Size and number of follicles stimulated e. Number of eggs retrieved f. History of PCOS 5. Outpatient management a. Light physical activity b. Drink 1 L of fluid a day. c. Possibly withhold hCG injection to prevent it. 6. Hospital management a. Fluid management b. Thrombosis prophylaxis Patient Case 8. L.L. is a 26-year-old woman (height 61 inches, weight 78 kg) who has been trying to conceive for 13 months without success. She and her male partner would like to conceive in the next year or so. Her BMI is 32 kg/m2, and she has moderate acne and hirsutism. Her menstrual cycle is fairly regular at 26–27 days. Her partner’s physical examination and semen analysis are normal. Her pelvic ultrasonography reveals polycystic ovaries, and she is given a diagnosis of PCOS. Which is the best first-line agent to recommend to L.L. to help her conceive? A. Consider weight loss and start clomiphene tablets. B. Continue trying to conceive; make no recommendations at this time. C. Start FSH injections. D. Start hCG injections. XV. S  EXUALLY TRANSMITTED INFECTIONS A. Herpes Simplex Virus (HSV) Infection 1. Characteristics a. Types: Genital herpes is caused by HSV; predominantly HSV-2 and, to a lesser extent, HSV-1. b. Diagnosed in in more than 500,000 individuals each year in the United States, with 11.9% of persons aged 14–49 years estimated to be infected. c. Treatment can partly control symptoms but does not affect the risk, frequency, or severity of recurrences after it is discontinued. d. Symptoms include itching, genital burning, vesicle formation, and ulcer formation. Most persons infected with HSV-2 have mild or unrecognized infections but shed virus intermittently in the anogentical area. e. After the primary infection, the virus is latent in the sacral dorsal root ganglia. f. From 50% to 80% of patients have recurrent infections (generally less severe and of shorter duration). 2. Diagnosis a. Culture and polymerase chain reaction: Preferred b. Serologic testing ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-608 Sexual & Reproductive Health 3. Therapy a. First-episode primary HSV infection; treat for 7–10 days (can extend treatment time if healing is incomplete) i. Acyclovir 400 mg orally three times daily ii. Famciclovir 250 mg orally three times daily iii. Valacyclovir 1 g orally twice daily b. Recurrent HSV infection i. The regimens listed in recurrent and suppressive section are primarily for HSV-2 type, not for HSV-1. No data are available regarding the efficacy of suppressive therapy for preventing transmission among persons with HSV-1. ii. Optimal episodic treatment requires initiation of therapy as soon as prodromal symptoms present or within 1 day of lesion onset. (a) Acyclovir 800 mg orally three times daily for 2 days (b) Acyclovir 800 mg orally twice daily for 5 days (c) Famciclovir 125 mg orally twice daily for 5 days (d) Famciclovir 500 mg orally for 1 day; then 250 mg orally twice daily for 2 days (e) Famciclovir 1000 mg orally twice daily for 1 day (f) Valacyclovir 500 mg orally twice daily for 3 days (g) Valacyclovir 1000 mg orally once daily for 5 days iii. Daily suppressive therapy recommended in patients with six or more episodes yearly (reassess annually the need for suppressive therapy) (a) Acyclovir 400 mg orally twice daily (b) Famciclovir 250 mg orally twice daily (c) Valacyclovir 500 mg/day orally (may be less effective in those who have frequent recurrences [10+ episodes/year]) (d) Valacyclovir 1000 mg/day orally c. Severe disease (e.g. disseminated infection, pneumonitis, or hepatitis) i. Should be hospitalized. ii. Treatment: Acyclovir intravenously 5–10 mg/kg every 8 hours for 2–7 days, followed by oral antiviral therapy for at least 10 days of total therapy 4. Herpes encephalitis a. Characteristics i. Caused primarily by HSV-1 ii. Spreads through neural routes during primary or recurrent infection iii. Primarily temporal lobe involvement with eventual hemorrhagic encephalitis iv. Frequent neurologic sequelae, and high mortality if untreated b. Diagnosis i. Signs and symptoms (nonspecific) (a) Headache (b) Fever (c) Speech disorders and behavioral changes (d) Focal seizures ii. Cerebrospinal fluid analysis (a) Moderate pleocytosis (generally lymphocytosis) (b) Normal glucose and moderately elevated protein iii. Brain biopsy (rarely performed) c. Therapy: Treatment should be intravenous acyclovir for 21 days. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-609 Sexual & Reproductive Health d. According to the 2021 STI guidelines, HSV-2 meningitis is also a rare complication of HSV-2 genital herpes infection. The clinical characteristics and diagnosis are similar to herpes encephalitis; however, the treatment regimen is intravenous acyclovir until clinical improvement followed by high-dose oral antiviral therapy to complete 10–14 days course of therapy. Patient Case Questions 9 and 10 pertain to the following case: D.H. is a 21-year-old woman who presents to the clinic with genital itching and vesicles on her vulva. She is sexually active with one partner who has a history of herpes. Her partner does not always use a condom when they have sex. She is initiated on acyclovir for this initial HSV infection. 9. Which statement is best to mention to D.H. regarding the treatment of her herpes infection? A. Treatment of the initial infection will prevent recurrent herpes infections. B. Treatment will shorten the duration of symptoms and infectivity of the initial infection. C. Treatment of the initial infection will decrease the severity of recurrent herpes infections. D. Treatment of the initial infection will prevent the virus from remaining latent in the dorsal root ganglia. 10. D.H. returns to the clinic 10 months after her initial herpes infection. She is troubled by all the recurrences she is having (seven to date). Which therapy is best to recommend? A. Valacyclovir 500 mg orally twice daily to be used for 5 days whenever she notices a recurrence beginning. B. Acyclovir 400 mg orally three times daily to be used for 10 days whenever she notices a recurrence beginning. C. Suppressive therapy with famciclovir 250 mg orally three times daily. D. Suppressive therapy with valacyclovir 500 mg daily orally. B. Syphilis (Treponema pallidum) 1. Characteristics a. A systemic infection caused by T. pallidum, a spirochete bacterium that is transmitted primarily through sexual activity or during pregnancy b. Untreated syphilis in pregnant women can lead to fetal demise and congenital infection. Cases of congenital syphilis have recently increased in the United States. c.  Persons who acquire T. pallidum remain chronically infected and can develop an array of clinical manifestations, which can progress in different stages (primary, secondary, latent, tertiary), with episodes of active clinical disease interrupted by periods of latent infection. d. Jarisch-Herxheimer reaction after initiating syphilis treatment i. Self-limited systemic reaction that typically begins within 4 hours after receiving the first antibiotic dose to treat syphilis, peaks in about 8 hours, and gradually resolves within 24 hours. ii. It results from transient release of inflammatory cytokines in response to spirochete lipoproteins lysed by antimicrobial therapy. iii. Most common symptoms associated with the Jarisch-Herxheimer reaction include fever, chills, tachycardia, myalgias, vasodilatation with flushing, accentuation of skin rash (if present pre-treatment), and dizziness (from mild to moderate hypotension). iv. Management consists of supportive therapy with antipyretics and intravenous fluids (if needed). Premedicating with antipyretics or corticosteroids before an antimicrobial dose does not prevent the Jarisch-Herxheimer reaction. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-610 Sexual & Reproductive Health 2. Diagnosis a. Dark-field examination and direct fluorescent antibody stains of exudate for spirochetes b. Nontreponemal (Venereal Disease Research Laboratory and Rapid Plasma Reagin); detect serum concentrations of antibody to cardiolipin. c. Treponemal (fluorescent treponemal antibodies and T. pallidum particle agglutination test): Detect antibodies to T. pallidum. d. Two testing algorithms may be used i. Traditional testing algorithm: Nontreponemal test, confirm with the treponemal test. ii. Reverse testing algorithm: Treponemal test; if positive, followed by quantitative nontreponemal, then confirm with treponemal test if nontreponemal is negative. 3. Primary syphilis a. From 10 to 90 days after exposure (mean 21 days) b. The primary symptom is the development of a chancre. c. The chancre resolves spontaneously in 2–6 weeks, even without treatment. d. Recommended treatment i. Benzathine penicillin G 2.4 million units intramuscularly in a single dose (adults) ii. If penicillin allergy: Doxycycline 100 mg orally twice daily, tetracycline 500 mg four times daily for 2 weeks, or ceftriaxone 1 g intramuscularly or intravenously daily for 10 days (if tolerated). If pregnant, avoid doxycycline or tetracycline, and consider ceftriaxone if there is supporting efficacy data or low concern for cross-reactivity; otherwise, consider penicillin desensitization. 4. Secondary syphilis or early latent syphilis (<1 year) a. 4–10 weeks after exposure b. Skin lesions: Characteristically on the palms and soles c. Latent phase begins when all symptoms have resolved. d. Recommended treatment i. Benzathine penicillin G 2.4 million units intramuscularly in a single dose ii. If penicillin allergy: Doxycycline 100 mg orally twice daily, tetracycline 500 mg four times daily for 28 days, or ceftriaxone 1 g intramuscularly or intravenously daily for 10 days (if tolerated). If pregnant, avoid doxycycline or tetracycline, and consider ceftriaxone if there is supporting efficacy data or low concern for cross-reactivity; otherwise, consider penicillin desensitization. 5. Late latent syphilis a. More than 1 year in duration or unknown duration b. Recommended treatment i. Benzathine penicillin G 2.4 million units intramuscularly every week for 3 weeks ii. If penicillin allergy: Doxycycline 100 mg twice daily or tetracycline 500 mg four times daily for 4 weeks 6. Tertiary syphilis a. Infectious granulomas and cardiovascular effects: Aortic insufficiency and aortitis b. Recommended treatment i. Benzathine penicillin G 2.4 million units intramuscularly every week for 3 weeks ii. If penicillin allergy: Treat in consultation with an infectious disease specialist. 7. Neurosyphilis a. Recommended treatment: Aqueous crystalline penicillin G 3–4 million units intravenously every 4 hours or continuous infusion (total of 18–24 million units per day) for 10–14 days b. Alternative regimen i. Procaine penicillin 2.4 million units/day intramuscularly plus probenecid 500 mg four times daily for 10–14 days ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-611 Sexual & Reproductive Health 8. ii. If penicillin allergy: Ceftriaxone 2 g/day intramuscularly/intravenously for 10–14 days, or patients should be desensitized and given penicillin (see CDC recommendations for skin testing and desensitization). Treatment of sexual partners a. Sexual partners should be presumptively treated if exposed within 90 days preceding the diagnosis in their partner. b. If exposure occurred more than 90 days prior, sexual partners should be tested and monitored closely or treated presumptively if serologic test results are not available immediately. C. Chlamydial Infection 1. Can lead to PID, ectopic pregnancy, and infertility 2. Less dysuria and penile discharge in men compared with gonococcal infection 3. Diagnosis a. Nucleic acid amplification testing (NAAT) i. Preferred method ii. Allows for a wide variety of FDA-cleared specimen types such as vaginal swabs, urethral swabs, endocervical, and urine b. Culture i. Requires endocervical swab (women) ii. Requires urethral swab (men) 4. Treatment a. Doxycycline 100 mg twice daily for 7 days b. Alternatives: Azithromycin 1 g orally for one dose (pregnancy) or levofloxacin 500 mg/day orally for 7 days c. Abstain from sexual intercourse for at least 7 days and until sexual partners are adequately treated. d. All sexual partners within the past 60 days should be assessed and treated. Expedited partner therapy is one strategy to improve treatment of sexual partners. It involves treating the sex partners of patients diagnosed with chlamydia or gonorrhea by providing prescriptions or medications to the patient to take to their partner without the health care provider first examining the partner. D. Gonococcal Infection 1. Penile discharge and dysuria are common in men, but women are often asymptomatic (which can lead to PID); symptoms in women include vaginal discharge and dysuria. 2. Diagnosis a. Nucleic acid amplification testing (NAAT) i. Preferred method ii. Allows for a wide variety of FDA-cleared specimen types such as vaginal swabs, urethral swabs, endocervical, and urine b. Culture i. Requires endocervical swab (women) ii. Requires urethral swab (men) 3. Treatment a. Uncomplicated gonococcal infections of cervix, urethra, and rectum: Ceftriaxone 500 mg intramuscularly for persons weighing less than 150 kg (for persons >150 kg, ceftriaxone 1 gram). If chlamydial infection has not been excluded, also treat with doxycycline 100 mg orally 2 times/day for 7 days. b. Gonococcal infection of the pharynx: Ceftriaxone 500 mg intramuscularly for persons weighing less than 150 kg (for persons > 150 kg, ceftriaxone 1 gram) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-612 Sexual & Reproductive Health c. Allergy to cephalosporins, may consider dual treatment with single dose of intramuscular gentamicin 240 mg plus azithromycin 2 g orally. Should consult an infectious disease specialist if patient has a cephalosporin allergy or immunoglobulin E–mediated penicillin allergy d. Abstain from sexual intercourse for at least 7 days and until sexual partners are adequately treated. e. All sexual partners within the past 60 days should be assessed and treated. E. Urethritis 1. Undiagnosed: Treat for both chlamydia and Gonococcus. 2. Nongonococcal a. Treat for chlamydia. b. Also consider Mycoplasma genitalium. i. Responsible for 15%–20% of nongonococcal urethritis (NGU), 20%–25% of non-chlamydial NGU, and about 30% of persistent or recurrent urethritis ii. Treatment: Doxycycline 100 mg orally 2 times/day for 7 days iii. Alternate: Azithromycin 1 g orally in a single dose or 500 mg orally for one dose then 250 mg orally for 4 days 3. Recurrent or persistent: Ensure adherence and no reinfection from infected partner; if these are ensured, treat with metronidazole or tinidazole for Trichomonas vaginalis and azithromycin. 4. All sexual partners within the past 60 days should be assessed and treated. F. Pelvic Inflammatory Disease 1. Ascending infection of the female genital tract involving primarily the fallopian tubes 2. Clinical presentation a. Lower abdominal tenderness b. Adnexal tenderness c. Cervical motion tenderness d. Oral temperature greater than 101°F e. Abnormal cervical or vaginal discharge f. Elevated erythrocyte sedimentation rate g. Elevated C-reactive protein h. Menorrhagia i. Dysuria 3. Sequelae: Abscess in pelvic or fallopian tubes, tubal occlusion, fibrosis, infertility; PID leads to infertility and ectopic pregnancies. 4. In general, sexually transmitted and caused by Neisseria gonorrhoeae, Chlamydia trachomatis, anaerobes, gram-negative facultative bacteria, and streptococci. 5. Treatment a. Parenteral treatment i.  Recommended regimens: (a) Ceftriaxone 1 g intravenously every 24 hours plus doxycycline 100 mg orally or intravenously every 12 hours plus metronidazole 500 mg orally or intravenously every 12 hours (b) Cefotetan 2 g intravenously every 12 hours plus doxycycline 100 mg orally or intravenously every 12 hours (c) Cefoxitin 2 g intravenously every 6 hours plus doxycycline 100 mg orally or intravenously every 12 hours. (d) Parenteral therapy can be discontinued 24–48 hours after clinical improvement and changed to orgal therapy for 14 days. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-613