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Therapeutics II > Block 5: Infertility > Flashcards

Block 5: Infertility Flashcards

1
Q

What is infertility?

A

Inability to conceive after 12 months of unprotected sexual intercourse

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2
Q

How is lifestyle linked to fertility?

A
  1. Increase in protien, fruits, veggies
  2. Men need zinc
  3. Exercise too much stop ovulation
  4. Fertility improves with BMI of 24–30 kg/m2
  5. Fertility decreased in those with BMI less than 19 kg/m2
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3
Q

What are the RF of infertility?

A
  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/m2 or more than 25 kg/m2 for women
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4
Q

How do you assess infertility?

A
  1. TIming of intercourse
  2. Modifiable RF (smoking, alcohol, caffeine, obesity)
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5
Q

How do you identify infertility cause?

A
  1. Semen analysis
  2. Confirmation of ovulation
  3. Documentation of tubal patency
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6
Q

How do you treat hyperprolactinemia?

A

Increased prolactin can cause infertility
First line: dopamine agonist (bromocriptine, carbergoline)
Second: surgery

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7
Q

How do you treat hypothyroidism?

A

Change menstrual cycle or sperm production

First line: thyroxine

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8
Q

What are the fertility agents?

A
  1. Clomiphene citrate
  2. Aromatase inhibitors(Femara (letrozole), Arimidex (anastrozole) –used off label)
  3. Human menopausal gonadotropin (hMG)
  4. Follicle-stimulating hormone (FSH)
  5. Human chorionic gonadotropin (hCG)
  6. Gonadotropin-releasing hormone analogs
    (GnRH)
  7. Metformin/ thiazolidinediones
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9
Q

What is the tx for ovulatory dysfunction?

A

First line: Clomiphene (Clomid®)

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10
Q

Clomiphene

Brand, MOA, Counseling, ADR, CI

A

Clomid
MOA: SERM
* Competes with estradiol for estrogen receptors at the hypothalamus
* Blocks estrogen negative feedback at the hypothalamus
* Increase in GnRH -> release of more FSH and LH -> stimulates ovaries

Counseling:
* Women failing to ovulate with 100 mg/day or failing to conceive following 3 to 6 months of ovulatory response to clomiphene should be considered for alternative treatments

ADR:
* Hot flashes
* Mild pelvic discomfort
* Breast tenderness

CI:
* Uncontrolled thyroid or adrenal dysfunction
* Primary ovarian failure or ovarian cysts
* Abnormal uterine bleeding
* Hepatic disease (hepatic metabolism)
* Pregnancy (category X)

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11
Q

What is the tx of PCOS?

A
  1. Weight loss, nutrition, exercise
  2. Insulin-sensitizing agents: First line: metformin 500-850mg BID and TZD
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12
Q

What are the gonadotropins?

A

LH, FSH

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13
Q

Indications and risks for gonadotropins?

A

Indication: Women with hypogonadism and PCOS
Risks: Multiple gestation, ovarian hyperstimulation

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14
Q

What is endometriosis?

A

Chronic disorder resulting in pain and infertility, endometrial tissue found outside the uterus

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15
Q

What are the risk facotrs for endometriosus?

A
  1. Menstruation-related problems
  2. Genital tract abnormalities
  3. Never had children/delayed pregnancy
  4. Elevated estrogen levels
  5. Genetic predisposition
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16
Q

What are the s/s of endometriosus?

A

Sx:
1. Pelvic pain
1. Subfertility
1. Dyspareunia
1. Dysmenorrhea
1. Abnormal menses
1. GI/GU symptoms
1. Asymptomatic

Signs:
1. Ligament tenderness
1. Tender nodules
1. Tender pelvic or adnexal mass
1. Small lesions on ovaries (dark brown, black, or blue lesions, nodules, and cysts)

17
Q

What are the goals of therapy?

A
  1. Remove tissue deposits
  2. Prevent progession of the condition
  3. Reduce the severity of pain
  4. Prevent or correct infertility
18
Q

What are the tx of endometriosus?

A

First: COC
Second: NSAIDs, GnRH agonist, Danazol, Progestin

19
Q

Therapy that doesn’t reduce scarring or cause reversal of endometriosis?

20
Q

NSAID agents for endometriosus?

MOA, Caution

A

Ibuprofen 400 mg q4-6h
Naproxen 250 mg q6-8h

MOA: Decreases PG production
Caution: Reactive airways disease, renal disease, GI ulcer

21
Q

GNRH agonist

MOA, Brand, ADR, Dosing

A

MOA:
* Prevents LH surge that occurs right before ovulation, which helps with timing of ovulation
* overstimulation = desensitization=downregulation=hypogonadism
* Induces “menopause” state

Brand: Leuprolide (Lupron), nafarelin (Synarel)
ADR: Hot flashes, vaginal dryness, irregular vaginal bleeding, mood changes, fatigue, and loss of bone density
Dosing: 1000 mg Ca daily while taking GnRH agonist

22
Q

What are the add-on therapy for GnRH?

A

Improves side effects and helps to reduce bone loss:
1. Norethinedrone 5 mg po daily
2. Norethindrone + Conjugated equine estrogen 5 mg po daily + 0.625 mg po daily
3. Norethindrone + Etidronate 2.5 mg po daily + 400 mg po daily x 14 days every 8 weeks

23
Q

Danazol

MOA, ADR, CI

A

MOA: Pituitary suppression of midcycle FSH/LH, Immunosuppressive
ADR: Androgenic: acne, hot flashes, increased LDL, weight gain, edema, hirsutism, myalgia (voice change is not reversible)
CI: Avoid in hyperlipidemia and liver disease, teratogenic

24
Q

Progestin agents for endometriosis?

A

Medroxyprogesterone 30-100 mg PO qd OR 150mg IM q3months
Norethindrone 15 mg qd
Megestrol 40 mg PO qd OR 3.75 mg IM q month

25
Progestins | MOA, ADR
**MOA:** Decreases endometrial buildup of tissue and decrease inflammation **ADR:** Delay in return to fertility, breakthrough bleeding, weight gain, edema, depression, mood swings, breast tenderness
26
Aromatase inhibitors | Products, MOA, ADR
Anastrozole (Arimidex) and Letrozole (Femara) **MOA:** Interrupt local estrogen formation within the endometriosis implants themselves **ADR:** Significant bone loss with prolonged use, HA, GI complaints, joint and bone pain, edema, sweating, flushing
27
1st line for infertility tx?
Conservative surgery: resection of lesions Radical surgery (other option): definitive tx, induces menopause
28
What are the surgical risks?
1. Pelvic damage 2. General surgical risks
29
What are the monitoring parameters for endometriosis?
1. Relieved within 2 months of therapy: If symptoms persist, consider different medical and/or surgical therapy 2. For infertility, most experts recommend 6 months of watchful waiting after surgical intervention 3. Lipids, BP measurements, BMI
30
What is dysmenorrhea?
Crampy pelvic pain that occurs with menses
31
What causes dysmenorrhea?
**Primary:** Caused by menstrual period, mediated by prostaglandins **Secondary:** Caused by menstrual period, mediated by prostaglandins, later in life
32
What is the tx plan for dysmenorrhea?
**Non Pharm:** * Topical heat therapy * Exercise * Low-fat vegetarian diet * Transcutaneous electric nerve stimulation * Acupressure/acupuncture **NSAIDs:** Scheduled dose starting 1 day prior to menses or prn, Trial for 2-3 menstrual cycles, Take with food or milk **OCs:** Trial of 2-3 months to determine efficacy **Depot medroxyprogesterone:** Renders most patients amenorrheic within 1 year, Lack of menses -> absence of PG release **Levonorgestrel-releasing IUD:** Reduces menstrual flow -> decrease in PG release If contraception is desired: OC is initial tx If contraception is not desired: Scheduled NSAIDs are initial treatment
33
What is the criteria for being diagnosed with PMDD?
1. Sx during last week of luteal phase, remit with menses 2. At least 5 of the following are present: Depressed mood, anxiety, affective lability, anger or irritability, decreased interest in activities, fatigue, difficulty concentrating, changes in appetite, sleep disturbance, feelings of being overwhelmed, physical symptoms **(One symptom must be depressed mood, anxiety, irritability or affective lability)** 3. Symptoms interfere with work/social relationships 4. Symptoms are not an exacerbation of an underlying psychiatric disorder
34
What is the non pharm tx for PMS/PMDD?
1. Chart sx for at least 2 cycles 2. Lifestyle modifications 3. Vitamin B6 50-100 mg daily 4. Calcium carbonate 1200 mg daily 5. Not recommended: herbal medicines, homeopathic remedies, dietary supplements
35
What is the pharm tx for PMS/PMDD?
**First:** SSRI **Alternatives:** * Clomipramine (TCA) * Venlafaxine (SNRI) * OC (Ethinyl estradiol/drospirenone +/- levomefolate (Beyaz®/Yaz®), Drospirenone (progesterone)) * Leuprolide (GnRH agonist): severe PMDD but expensive

Therapeutics II (30 decks)

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