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Sexual & Reproductive Health ii.  Alternative regimens: (a) Ampicillin/sulbactam 3 g intravenously every 6 hours plus doxycycline 100 mg intravenously or orally every 12 hours (b) Clindamycin 900 mg intravenously every 8 hours plus gentamicin 2 mg/kg body weight intravenously or...

Sexual & Reproductive Health ii.  Alternative regimens: (a) Ampicillin/sulbactam 3 g intravenously every 6 hours plus doxycycline 100 mg intravenously or orally every 12 hours (b) Clindamycin 900 mg intravenously every 8 hours plus gentamicin 2 mg/kg body weight intravenously or intramuscularly for a single dose then 1.5 mg/kg body weight every 8 hours b.  Treatment for M. genitalium should be considered if PID treatment for 7–10 days has failed. Recommended to start moxifloxacin 400 mg orally daily for 14 days. c. Sexual partners of patients with PID within the past 60 days should be tested and treated. Patient Case Questions 11 and 12 pertain to the following case: M.A. is a 24-year-old woman who presents to the emergency department with severe abdominal pain, fever, dysuria, and a vaginal discharge. She is sexually active. Her medical history is unremarkable except for recurrent genital herpes (one or two episodes a year). Her medications on admission include birth control pills (ethinyl estradiol 30 mcg/desogestrel 0.15 mg) and fluticasone nasal spray as needed. On physical examination, M.A.’s vital signs include temperature 101.2°F (38°C), heart rate 92 beats/minute, respiration rate 15 breaths/minute, and blood pressure 117/75 mm Hg. M.A. has adnexal tenderness, cervical motion tenderness, and a vaginal discharge. 11. Which is the best empiric therapy for M.A.? A. Ampicillin/sulbactam intravenously 2 g every 6 hours for 14 days B. Metronidazole 500 mg intravenously three times daily for 7 days C. Cefotetan 2 g intravenously every 12 hours with doxycycline 100 mg orally every 12 hours for 14 days D. Ceftriaxone 125 mg intramuscularly once with doxycycline 100 mg intravenously twice daily for 7 days 12. Which statement is best for M.A. to tell her sexual partners? A. There is no need for concern because this condition is not transmittable to or acquired from a sexual partner. B. Her partner can resume having sexual intercourse with M.A. as soon as her symptoms improve. C. If her partner has had sex with M.A. within the past 60 days, he should be assessed for possible treatment. D. Her partner does not need to be tested for human immunodeficiency virus (HIV) because there is no relationship between HIV and this condition. G. Bacterial Vaginosis 1. Malodorous vaginal discharge caused by an overgrowth of anaerobic bacteria (circumventing the normal flora of Lactobacillus); more than 50% with bacterial vaginosis are asymptomatic. 2. Infection risk is increased in relation to sexual activity, but it is unknown whether acquired through sexual partner. 3. Diagnosis is based on a malodorous vaginal discharge that is high in pH, contains clue cells, and is whiff test positive (fishy odor after potassium hydroxide 10% added to sample). 4. Bacterial vaginosis has been implicated in PID and is possibly linked to endometritis. 5. Treatment a. Nonpregnant women: Metronidazole 500 mg orally twice daily for 7 days or clindamycin 2% cream, 1 full applicator intravaginally at bedtime for 7 days, or metronidazole 0.75% gel, 1 full applicator intravaginally once daily for 5 days ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-614 Sexual & Reproductive Health b. Alternatives: Clindamycin ovules 100 mg intravaginally at bedtime for 3 days, clindamycin 300 mg orally twice daily for 7 days, tinidazole 2 g orally once daily for 2 days, tinidazole 1 g orally once daily for 5 days, secnidazole (Solosec) 2 g packet of granules, sprinkle on pudding, applesauce, or yogurt (do not chew or crush granules, do not dissolve in a liquid) and consume within 30 minutes c. Treatment of sexual partners is not necessary. H. Trichomoniasis 1. Caused by T. vaginalis 2. Men often have no symptoms, but women generally have a malodorous, yellow-green vaginal discharge and vaginal irritation. 3. Diagnosis most sensitive with NAAT, many times detecting five times more T. vaginalis infections than wet-mount microscopy. 4. Treatment a. Recommended treatment for women: Metronidazole 500 mg orally 2 times/day for 7 days b. Recommended treatment for men: Metronidazole 2 g orally in a single dose c. Alternative: Tinidazole 2 g orally in a single dose d. All sexual partners should be treated. e. Metronidazole-allergic patients should be desensitized. I. Vulvovaginal Candidiasis 1. Seventy-five percent of women have at least one episode (40%–45% will have many episodes). 2. Symptoms include pruritus and vaginal discharge. 3. Predisposing factors include OCs, pregnancy, obesity, diabetes mellitus, corticosteroid use, chemotherapy, and antibiotics. 4. Diagnosed by symptoms and potassium hydroxide smear 5. Therapeutic regimens: 1- and 3-day regimens may take up to 7 days for full effect (Table 20). Table 20. Therapeutic Regimens for Treatment of Vulvovaginal Candidiasis Drug Dose Length of Therapy Butoconazole Clotrimazole 2% cream: 5 g intravaginally 1% cream: 5 g intravaginally at bedtime (OTC) 2% cream: 5 g intravaginally at bedtime (OTC) 2% cream: 5 g intravaginally at bedtime (OTC) 4% cream: 5 g intravaginally at bedtime (OTC) 100-mg vaginal suppository at bedtime (OTC) 200-mg vaginal suppository at bedtime (OTC) 1200-mg vaginal suppository × 1 (OTC) 0.4% cream: 5 g intravaginally at bedtime 0.8% cream: 5 g intravaginally at bedtime 80-mg vaginal suppository at bedtime 6.5% ointment: 5 g intravaginally (OTC) 150-mg oral tablet 1 dose 7–14 days 3 days 7 days 3 days 7 days 3 days 1 dose 7 days 3 days 3 days 1 dose 1 dose 150 mg every 72 hours for 2–3 doses (severe infection) Miconazole Terconazole Tioconazole Fluconazole OTC = over the counter ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-615 Sexual & Reproductive Health 6. Recurrent vulvovaginal candidiasis (three or more episodes a year): Needs prescription drug treatment, not OTC. a. Initial treatment for 7–14 days or fluconazole 100-, 150-, or 200-mg dose every third day for three doses b. Maintenance: Oral fluconazole 100, 150, or 200 mg/week for 6 months c. Consider conditions precipitating recurrent vulvovaginal candidiasis: HIV, diabetes mellitus. d. Oteseconazole 150 mg capsule i. FDA approved in 2022 for recurrent vulvovaginal candidiasis in females who are not of reproductive potential. It should only be used in females who are postmenopausal or have permanent infertility (e.g., tubal ligation, hysterectomy, salpingo-oophorectomy). ii. Through a tetrazole metal-binding group, oteseconazole offers greater selectivity for fungal CYP51 than human CYP enzymes and thus causes fewer off-target CYP-induced drug interactions. iii.  Two dosing approaches: (a) Day 1: Oteseconazole 600 mg (single dose); Day 2: oteseconazole 450 mg (single dose); beginning on Day 14: oteseconazole 150 mg once weekly for 11 weeks (weeks 2–12) (b) Days 1, 4, and 7: Fluconazole 150 mg; Days 14–20: oteseconazole 150 mg once daily for 7 days; beginning on Day 28: oteseconazole 150 mg once weekly for 11 weeks (weeks 4–14) iv. Headaches and nausea are most commonly reported adverse effects 7. Prophylaxis needed for vulvovaginal candidiasis while taking antibiotics; recommend OTC 7-day treatment and use a full applicator at bedtime while taking antibiotics; oral fluconazole is also sometimes used. 8. Pregnant women: Drugs of choice are topical azoles, 7-day treatment. XVI. MALE SEXUAL DYSFUNCTION A. Types 1. Reduced libido from organic or psychological causes a. Low serum testosterone concentrations b. Elevated concentrations of serum prolactin 2. Ejaculation a. Premature b. Retarded c. Absent d. Retrograde 3. Erectile dysfunction a. Persistent (at least 6 months) inability to achieve or maintain an erection of sufficient duration and firmness to complete satisfactory intercourse through vaginal penetration b. Psychological c. Organic d. Mixed e. Causes i. Vasculogenic (a) CVD (hypertension, coronary artery disease) (b) Diabetes mellitus (c) Hyperlipidemia (d) Smoking (e) Major pelvic surgery or radiotherapy ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-616 Sexual & Reproductive Health ii. Neurogenic (a) Central causes: Degenerative disorders, spinal cord trauma or disorders, stroke, CNS tumors (b) Peripheral causes: Type 1 or 2 diabetes, chronic renal failure, neuropathy, abdominal surgery, or urethral surgery iii. Hormonal abnormalities because of excess prolactin (hyperprolactinemia) or decreased testosterone concentrations (hypogonadism), hyperthyroidism or hypothyroidism, hypercortisolism or hypocortisolism iv. Medical conditions such as angina, shortness of breath because of asthma or chronic obstructive pulmonary disease v. Drugs such as antihypertensives, psychiatric medications (antidepressants and antipsychotics), antiandrogens, recreational drugs vi. Anatomical (a) Hypospadias (b) Micropenis (c) Peyronie’s disease vii. Trauma: Penile fracture, pelvic fracture B. Treatment of Erectile Dysfunction 1. Control risk factors a. Stop smoking. b. Control chronic conditions (diabetes, hyperlipidemia, hypertension) c. Decrease alcohol intake. d. Discontinue illicit drugs. e. Lose weight and increase physical activity. f. CVD must be stabilized and assessed before treatment; must assess whether sexual activity in stable relationship does not increase risk of cardiovascular events or put undue stress on heart. 2. Nonpharmacologic treatment a. Vacuum pump devices (may cause adverse effects such as pain and bruising) b. Venous constriction rings (may cause adverse effects such as pain and bruising) c. Shockwave therapy d. Penile implant e. Counseling 3. Testosterone replacement if testosterone concentrations are low (e.g., less than 300 ng/dL) a. Oral testosterone undecanoate oral capsules (Jatenzo): Recommended dosage is 237 mg by mouth in the morning and evening with food. May decrease dose to 158 mg twice daily or maximal dose of 396 mg twice daily, depending on testosterone concentration obtained 6 hours after the morning dose after 7 days of administration. b. Depot intramuscular injection of testosterone enanthate 200 mg or cypionate 300 mg every 2–4 weeks c. Transdermal patches placed daily: Androderm 2–6 mg at bedtime on back, abdomen, or arms; rotate sites; available in 2 mg/day and 4 mg/day transdermal systems d. Testosterone gel applied every morning i. Testim 1% has 50 mg of testosterone per tube; apply to shoulders, upper arms only. ii. AndroGel 1.62% packets, 20.25 mg and 40.5 mg of testosterone or in a pump; 2 pumps = 40.5 mg of testosterone and should be applied once daily in the morning. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-617 Sexual & Reproductive Health iii. AndroGel 1% packets available in 25 mg and 50 mg of testosterone or in a pump; 4 pumps = 50 mg of testosterone that should be applied once daily in the morning; may be applied to shoulders, upper arms, and abdomen; should not be applied to genitals, chest, or back. iv. Fortesta 2% gel, may apply 10–70 mg; 1 pump = 10 mg; apply to thighs; avoid genitals. v. Vogelxo 1% 50 mg/one tube or packet and Vogelxo 1% Pump (4 actuations, 1 actuation = 12.5 mg); apply to clean, dry, intact skin of shoulders or upper arms; do not apply to genitals or abdomen. e. Axiron topical solution, apply 60 mg (1 actuation = 30 mg) to underarms once daily. f. Testopel 75-mg pellet, implanted; provides hormone for 3–4 months. g. Striant 30-mg buccal system; placed on gum tissue above incisors with flat section facing cheek; used twice daily. h. Natesto nasal gel, recommended dosage is 11 mg of testosterone (5.5 mg/actuation, 2 pump actuations, 1 per nostril) applied intranasally three times daily; should not be administered with sympathomimetic decongestants (e.g., oxymetazoline). i. Adverse effects and contraindications i. Contraindicated in patients with prostate cancer ii. Patches may cause redness and irritation at site of application. iii. May cause increase in blood pressure, acne, enlarged prostate, liver toxicity, cholesterol changes, edema, polycythemia. j. Monitor serum testosterone within 1–3 months and at 6- to 12-month intervals. k. If no improvement after 3 months, may discontinue treatment. l. The 2020 ACP guidelines recommend the following: i. Discussions of testosterone treatment in men with age-related low testosterone and sexual dysfunction should include the potential benefits, harms, costs, and patient preferences. ii. Symptoms should be reevaluated within 12 months (and then periodically). Testosterone should be discontinued if sexual function does not improve. iii. Given lower costs, intramuscular testosterone rather than transdermal should be considered. Efficacy and risk profiles are similar between the formulations. 4. Phosphodiesterase (PDE) inhibitors (first-line drug therapy for men without contraindications to use) (Table 21) a. Sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra/Staxyn), avanafil (Stendra) b. Inhibits PDE-5 in the penile tissue, preventing the breakdown of cyclic guanosine monophosphate, thus increasing smooth muscle relaxation in the corpora cavernosa and increasing penile rigidity. c. Adverse effects: Headache, hot flashes, heartburn, diarrhea, myalgias, hypotension, dizziness, difficulty discriminating blue from green d. Contraindications, cautions, and drug interactions i. Contraindicated with nitrate use; should not be used together. ii. Use caution with CVD, hypotension, uncontrolled hypertension, MI, or stroke within 6 months, life-threatening arrhythmias, penile deformities, renal or hepatic dysfunction, and degenerative retinal disorders. iii. Drug interactions such as protease inhibitors; decrease PDE inhibitor dosage by half in some cases; precautions with CYP3A4 inhibitors and macrolides because they increase PDE inhibitor levels; may also need to decrease PDE inhibitor doses in these situations or possibly avoid combined use with CYP3A4 inhibitors. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-618 Sexual & Reproductive Health Table 21. Summary of Phosphodiesterase-5 Medications Name Sildenafil (Viagra) Dosage 50 mg PO 1 hr before intercourse (dose range 25–100 mg) Vardenafil (Levitra) 10 mg PO 1 hr before intercourse (dose range 5–20 mg) Vardenafil oral 10 mg PO 1 hr before intercourse disintegrating tablet Tadalafil (Cialis) 5 mg PO up to 36 hr before intercourse (dose range 5–20 mg) 2.5–5 mg PO daily for daily dosing Avanafil (Stendra) 100 mg PO 30 min before intercourse (dose range 50–200) Comments May require hepatic and renal dosage adjustments Take on empty stomach May require hepatic dosage adjustment Fatty meal delays onset Not recommended with hepatic conditions Do not use with CYP3A4 inhibitors May require hepatic or renal dose adjustments Food has no effect on onset Fatty food may delay onset PO = by mouth 5. 6. Alprostadil (second-line therapy if PDE-5 inhibitors fail) a. Caverject intracavernosal injection 2.5–40 mcg b. MUSE urethral pellets 125–1000 mcg c. Effect may last 30–90 minutes. d. Adverse effects: Penile pain, cavernosal scarring, priapism, hypotension e. Drug interactions: Do not use with PDE inhibitors. Yohimbine a. Derivative of African yohimbine tree b. α2-Antagonist c. Efficacy controversial; not recommended according to the American Urological Association guidelines. d. Adverse effects: Headaches, dizziness, insomnia, and anxiety e. Dose: 5.4 mg orally three times daily C. Treatment of Premature Ejaculation 1. Antidepressants: Off-label use a. Selective serotonin reuptake inhibitors: Fluoxetine, paroxetine, sertraline b. Tricyclic antidepressant: Clomipramine c. Continuous (daily), or episodic dosing 2–12 hours before intercourse 2. Topical anesthetics: Lidocaine/prilocaine cream (EMLA [eutectic mixture of local anesthetic]) 2.5 g applied to the glans penis and penile shaft 20–30 minutes before intercourse Patient Case 13. A 65-year-old man presents to his physician with symptoms that are determined to be erectile dysfunction. He has a history of hyperlipidemia, gastroesophageal reflux disease, and glucose intolerance. His medications include atorvastatin 40 mg orally daily, omeprazole 20 mg orally daily, and aspirin 81 mg orally daily as tolerated. He states that he has heard of medications to help with his symptoms but does not want to have to plan his intimate moments. Which drug would work best for this patient? A. Tadalafil B. Avanafil C. Yohimbine D. Bupropion ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-619 Sexual & Reproductive Health Answer 6 Table.* Drugs Interfering with Oral Contraceptive Efficacy Increased Decreased Ascorbic acid Anticonvulsantsa Acetaminophen-scheduled Atorvastatin Rosuvastatin Ginseng NNRTIsd Protease inhibitors Tranexamic acid Voriconazole e Oral Contraceptives Interfering with the Efficacy of OtherDrugs Increased Decreased Antibiotics Rifampin Theophylline Benzodiazepinesb Theophylline and caffeine Cyclosporine Corticosteroids Benzodiazepinesc Warfarin Thyroid agents Hypoglycemics St. John’s wort Alcohol Methyldopa NNRTI–nevirapine Protease inhibitorsf Sulfonamides Griseofulvin Bosentan β-Blockers Tricyclic antidepressants Ropinirole Zolmitriptan Metformin Amprenavir Lamotrigine Fosamprenavir Tacrolimus Modafinil Note. *Table not all-inclusive of all drug interactions; some interactions may exist that are not listed in this table. a Barbiturates, phenytoin, primidone, carbamazepine, oxcarbazepine, felbamate, topiramate, vigabatrin b Alprazolam, chlordiazepoxide, diazepam c Temazepam d Delavirdine, efavirenz e Atazanavir, indinavir f Nelfinavir, ritonavir, lopinavir/ritonavir, amprenavir NNRTI = nonnucleoside reverse transcriptase inhibitor ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-631