Pharmacology- Women's Fertility Drugs (Ch. 34) & Men's Fertility Drugs (Ch. 35)

What are the therapeutic uses of testosterone?

Tx of conditions related to androgen deficiency Hypogonadism: Testosterone used as replacement therapy Condition where testes produce inadequate amounts of testosterone § Most common reason for androgen therapy Puberty is delayed until tx with long-acting parenteral dose is started Testicular failure: Testosterone used as replacement therapy § Tx improves libido, ejaculation amount and secondary characteristics § Tx does not reverse infertility ○ Delayed puberty ○ Other Uses COPD and AIDs: Testosterone may slow decline of patients with these muscle wasting diseases

What can Male infertility drugs help with?

correct hormonal imbalances that cause infertility, thereby resolving sperm issues: (oligospermia or asthenospermia) and/or helping with hypogonadotropic hypogonadism (condition in which signal for testicles to produce sperm is absent).

What are androgens?

male sex hormones- produced in testes, ovaries, and adrenal cortex.

What is the MOA of Clomiphene Citrate?

mechanism of action of CC is unknown. binds at estrogen receptor sites in hypothalamus and pituitary, thereby causing in an increase in FSH and LH. This increase leads to maturation of follicles and ovulation. Women with PCOS (polycystic ovary syndrome) may need concurrent treatment for hyperinsulinemia with metformin. Metformin helps regulate the menstrual cycle and promote ovulation when used singly; however, when it is paired with CC, the success rate is increased.

What are some nursing Interventions and Evaluation for Testosterone?

nurse should monitor the following in the patient taking replacement testosterone: ○ daily weights ○ I&O ○ changes in BP and lab values ○ protein intake and calories ○ sleep patterns ○ signs of injection site infection or allergic reaction. interventions may be needed based on evaluation of patient: ○ Report weight gain of >5 lbs in a week and check for edema. ○ Adjust dosage to keep testosterone levels WNL ○ DC tx if patient shows signs of hypercalcemia. ○ Make changes to plan of care when necessary.

What are some cultural considerations?

o In male-dominated cultures, women are often blamed for infertility and/or may immediately place blame of infertility on themselves. o Conflicts between religious and/or cultural traditions and use of reproductive technology may be an ongoing challenge that creates much stress and anxiety for couples. ○ Support and appropriate resources should be suggested to such couples and utilized in such instances. o Women may need to remain covered as much as possible during exams in order to maintain patient dignity and respect. o Often patients will combine conventional medicine with traditional medicine for infertility issues. ○ A thorough hx of conventional medicine uses is necessary in order to determine appropriate tx. o If a patient has a language barrier, appropriate interpreter is necessary. o HCPs of same gender and/or culture may be preferred by patients dealing with sensitive issues such as infertility. o Support should be provided to the patient for physical, psychological, emotional, and spiritual aspects of infertility, and appropriate interventions should be put in place.

Discuss some pharmokinetics of testosterone

o Secretion of testosterone happens in both men and women; however, amount is much greater in men. o Only 2% of testosterone is unbound, and it is this portion that is active. ○ This percentage is lower for women due to their higher estrogen levels (estrogen causes increased production of sex hormone-binding globulin or SHBG). o PO administration of testosterone requires higher doses to account for loss of up to 50% of drug when it is metabolized by liver. o PO doses only available for synthetic androgens because these have a longer half-life. o onset and peak of testosterone IM are currently unknown. duration is 2-4 weeks.

What role to androgens play in growth and management of males?

Androgens play a part in growth and management of male sex characteristics, including sexual organs (accessory) and processes and bone and muscle growth; control development and maintenance of cellular metabolism.

Key points of Women's Fertility Drugs

o There are numerous causes of infertility for women and men. o successful tx of infertility depends on an accurate diagnosis. o Drugs used to tx female infertility do this: ○ promote follicular maturation ○ stimulate ovulation ○ promote ovulation control. o Clomiphene citrate (CC) is the most commonly used ovulation stimulant. o Assessment of patient's menstrual hx and a complete physical examination, including speculum and bimanual exams, are required prior to initiation of CC. o An exhaustive battery of diagnostic tests is used to determine the cause of infertility prior to initiation of CC. o Undiagnosed vaginal bleeding, pregnancy, and uterine fibroids are contraindications for CC. o CC can cause existing ovarian cysts to enlarge. o Women who take CC are at increased risk for multiple gestations. o Teaching regarding CC should primarily focus on ovulation cycle.

What are some COUPLE pre-admin assessment points Clomiphene Citrate?

o complete assessment of couple's sexual practices ○ use of lubricants ○ timing and technique of intercourse. o couple's mental health status ○ provide a referral to a support group or counseling as needed. ○ Infertility can be isolating, because many couples experiencing infertility may have several peers who are pregnant or already have children. o Prepare couple for exhaustive battery of diagnostic tests they will undergo to evaluate cause of infertility. Once the cause of infertility is determined, conditions that contraindicate tx of choice must be ruled out. o Help couple discuss their feelings in a safe, supportive environment. It is particularly important that couple's interpretation of their infertility be explored, along with its impact on their relationship.

How would you evaluate the outcomes of Clomiphene Citrate?

o desired outcome for CC tx in infertility is for patient to become pregnant, resulting in birth of an infant. o If this outcome is not obtained, alternatives to childbearing should be discussed and appropriate support should be arranged to avoid adverse impact of failed treatment on couples' self-esteem and/or harm to their relationship. couple should be encouraged to express feelings and voice concerns about tx success and/or failure throughout entire experience.

Keypoints of testosterone?

Androgens--male sex hormones. Anabolic hormones are also androgenic. Testosterone ○ primary androgen and is an anabolic steroid. ○ primarily secreted from testes ○ also secreted in smaller amounts by adrenal cortex. ○ responsible for development and maintenance of male sex organs and secondary characteristics. ○ clinically used for tx of androgen deficiency, including hypogonadism, testicular failure, and delayed puberty. ○ secreted in both men and women, but active portion (unbound testosterone) is greater in men. Patients taking testosterone therapy should be monitored for changes in affect and muscle tone. · Baseline physical and lab assessments enable nurse to compare changes in liver function and thyroid function. Diabetic patients may need to decrease insulin; androgens decrease blood glucose. Oral anticoagulants have an increased effect when used with testosterone. Androgen therapy is contraindicated in patients with certain conditions, such as a history of MI, prostate cancer, and benign prostatic hypertrophy. · Nurses should administer IM injections deep into gluteal muscle and monitor injection site for irritations. testosterone cypionate or enanthate is used for prolonged therapy. For patients using Androderm, two patches are applied daily to arms, back, or upper buttocks. Patients experiencing frequent erections (priapism) should notify their HCPs so changes to dose can be made.

What is the Dosage and Administration of Clomiphene Citrate?

o given during days 5-9 of menstrual cycle. o first administered in 50-mg/day PO dose. o If ovulation does not occur, this dose can be increased by 50 mg/day for a second course of 5 days. o Once a dose is established, that dose should be given for a max of three sequential cycles. o Doses > 100 mg/day are not recommended. o Each new regimen should begin no sooner than 30 days after previous medication regimen. When ovulation occurs (usually within 5 to 10 days after \last CC dose), intercourse should take place at least every other day.

What are some Contraindications of Testosterone?

older male patients on androgen therapy have an increased risk of benign prostatic hypertrophy (BPH) and prostate cancer. · Contraindications: ○ Nephrosis ○ Hypercalcemia ○ Pituitary insufficiency ○ Benign prostatic hypertrophy (BPH) ○ Hepatic dysfunction ○ Prostate cancer ○ History of myocardial infarction § *Cautions: □ high BP □ high cholesterol

How would you administer testosterone via transdermal pathch?

○ Apply to back, abdomen, upper arms, or thighs (avoid bony prominences and scrotum) ○ Change site every 7 days ○ Inform patient that hypogonadism returns within 24 hours of removing patch Dosage: Androderm and Testoderm TTS Patch = 4 mg/day (adjust dose based on testosterone levels)

How would you administer testosterone via topical solution?

○ Apply to both axillary (under arm) areas around same time each morning ○ Avoid getting site wet or washing within first 2 hours after application ○ Wait until completely dry, as medication can be transferred to other persons via skin or clothing contact ○ Do not apply to genitals ○ Dosage: Axiron = 60 mg once a day

How would you administer testosterone Buccal?

○ Apply to gums and hold until administration adheres; adhesion can take up to 30 seconds ○ Remove old administration before a new one is applied ○ Caution patient not to chew or swallow buccal administrations ○ Dosage: Striant = 30 mg every 12 hours

What are Male factors that can result in infertility?

○ Genetic ○ Seminal ○ Transport ○ Testicular ○ Endocrine ○ age-related factors ○ drug use ○ excessive alcohol intake ○ exposure to pollution ○ tobacco use ○ scrotal heat exposure ○ infectious processes ○ Malnutrition ○ Allergies -autoimmunity to sperm

What are Female factors that can result in infertility?

○ Genetic ○ Tubal ○ Peritoneal ○ Ovarian ○ Cervical ○ Uterine ○ Endocrine ○ age-related factors ○ drug use ○ excessive alcohol intake ○ tobacco use --Malnutrition

What are the Dosage and Administration of Testosterone

○ PO ○ Buccal ○ Transdermal ○ IM Assess desired sexual maturation and balance of growth before choosing between an androgen or an anabolic steroid. ·

What are some side effects of testosterone?

○ Priapism: frequent erections (seen in patients with hypogonadism) § Reduced dose may be required Gynecomastia: enlarged mammary glands ○ Low urine output § Patient should be assessed for prostatic hypertrophy ○ Other side effects: § GI disturbances § Insomnia § low libido § Acne ○ Side effects of prolonged use include: § Stopped spermatogenesis (formation of spermatozoa) § Oligospermia: low sperm count § Asthenospermia: low sperm motility

What are some Adverse Effects of Clomiphene Citrate?

○ breast tenderness ○ Weakness ○ Dizziness ○ increased appetite ○ breast pain ○ hot flashes ○ uterine bleeding ○ blurred vision ○ HAs ○ abdominal bloating ○ N/V ○ visual changes ○ Reversible hair loss has also been noted. o effects of CC on development of human fetus are unclear, but developmental abnormalities have been reported in animals. o Neural tube defects have been reported, but controlled studies have not confirmed this suggested finding.

When a fertility tx is prescribed to a male, it is nurse's responsibility to?

○ ensure patient understands what it means to be compliant with medication ○ how to administer medication ○ how medication works ○ possible side effects.

What Factors related to couples that can result in infertility?

○ intercourse frequency ○ intercourse timing ○ sexual technique ○ immune response to sperm.

Low levels of testosterone in males are associated with:

○ low libido ○ Impotence ○ decreased muscle tone -testicular atrophy.

Labs for patients receiving androgen therapy may show elevated:

○ serum cholesterol ○ BUN ○ Creatinine ○ Hematocrit ○ liver function ○ elevated urine 17-ketosteroids (by-product of breakdown of androgens).

What are some pre-admin information you want to get from your male patient prior to admin of testosterone?

Ask why androgen therapy is necessary for patient. Ask what patient thinks about androgen therapy. · Record ○ patient's weight ○ BP ○ Liver function ○ thyroid function · Draw labs ○ Hgb ○ Hct ○ Glucose ○ Creatinine ○ Lipids ○ Electrolytes ○ CBC · Ask if patient is on any anticoagulation therapy. · Evaluate patient's affect. · Some patients on large doses of testosterone may become more aggressive.

What are some PATIENT pre-admin assessment points for Clomiphene Citrate?

Assessment of Patient - general health history drug and herbal product use. physical examinations · speculum and bimanual exams. reproductive and sexual histories pay attention to any: □ history of abnormal Pap testing and tx □ vaginal infections and/or STIs and tx □ past use of contraception methods □ pelvic surgery □ past and/or present gynecologic abnormalities □ pregnancy and birth complications ○ complete menstrual history- including: · menarche (LNMP) last menstrual period □ Length □ Duration □ flow of bleeding any other signs or symptoms related to the menstrual cycle.

The wide variety of medical treatments used for infertility fall into what category?

Assisted reproductive technology (ART).

What is the Therapeutic Use of Clomiphene Citrate?

CC is used to stimulate ovarian follicle growth.

What are the drugs that are most commonly used to treat infertility?

Drugs that promote follicular maturation, stimulate ovulation, and promote ovulation control

What are some teaching points you can make as a nurse regarding testosterone?

General Teaching ○ Medication should be taken just as prescribed § patient compliance is essential for successful tx. ○ Expected side effects and those that would require patient to be seen by a medical professional should be explained to patient. ○ Patient monitoring at HC facility is necessary throughout course of tx. ○ Attention should be paid to changes in muscle strength. ○ Assessment of area of gums where buccal administrations have been placed is necessary. • Diet ○ essential nutrients is important for patients taking testosterone therapy. ○ Weekly body weights should be obtained and patient should be monitored for edema § if edema occurs then sodium intake should be decreased. § Increased fluid intake can help prevent kidney stones in patients with high calcium levels. Self-Administration ○ PO forms of testosterone should be taken with food

What are some teaching points that can be made to the patient regarding Clomiphene Citrate?

General Teaching ○ Changes in basal body temperature and changes in cervical mucus are indicative of ovulation status. ○ Couples should evaluate and record day 1 of menstrual cycle. ○ For prime ovulation to be predicted, a 0.5° F drop in basal body temperature followed by a 1° F rise in basal body temperature is needed. ○ Ovulatory kits can be used to help couples determine prime time for sexual intercourse. ○ Couples should be taught to engage in intercourse 4 days before ovulation and 3 days after ovulation. ○ Couples should engage in intercourse every other day if low sperm count is an infertility factor. · Skipping a day will help maximize sperm count. ○ medication should be taken at same time daily to enhance medicine's effects and sustain therapeutic blood levels. ○ Couples should be encouraged to express feelings and voice concerns about tx success and/or failure throughout treatment.

Give some pharmokinetic information about Clomiphene Citrate

Half-life of 5-7 days Easily absorbed from GI tract Metabolized in liver E xcreted in feces via biliary elimination

What are Adverse Effects of Testosterone?

Hypercalcemia--DC if signs of this · Infrequent effects ○ Polycythemia ○ lower extremity edema ○ Dizziness ○ HAs ○ skin rash ○ Depression ○ Bleeding ○ Chills ○ muscle cramps · Hepatic carcinoma (seen with select long-term therapy androgens) · Elevated: ○ serum cholesterol ○ Hematocrit ○ thyroid levels · Rare complications: ○ hepatic peliosis (blood-filled cysts) ○ Necrosis ○ Tumors ○ Leucopenia · Altered mood · aggressiveness

What are some Cultural Considerations regarding testosterone?

Not all people have same beliefs about sexuality and expression of it. Be considerate of different cultural views related to the use of fertility tx drugs. Consider: ○ How does patient feel about sexual expression? ○ What does patient think about different types of relationships? ○ Does patient's culture prevent him from talking about sexual subjects or showing any body parts?

What are some interacting drugs with testosterone?

Oral anticoagulants Calcitonin and parathyroid hormones Antidiabetic agents Corticosteroids Barbiturates: phenytoin, phenylbutazone □ lesterol □ heart disease □ kidney disease -seizure disorders

What is the 1st line of drug treatment for ovulatory dysfunction disorders?

Oral drug therapy

What are some Ovulatory dysfunction disorders?

Polycystic ovary syndrome (PCOS) and other metabolic syndromes, are the leading cause of infertility in women.

What are interactions and interventions for each of testosterone?

Results: Increased anticoagulant effect INTERVENTION: Decrease dosage of anticoagulant Antagonized; effect of both medications is decreased INTERVENTION:Decrease dosage of anticoagulant Decreased blood sugar in patients with diabetes INTERVENTION: Reduce dosage of antidiabetic agents Exacerbation of edema common in androgen therapy INTERVENTION: Do not administer concurrently Decreased androgen effect INTERVENTION: Increase dose of androgen if necessary

What kind of steroid is testosterone and where is it produced?

Testosterone is an anabolic steroid that is produced primarily in testes, although small amounts are produced in adrenal cortex.

What is testosterone directly related to ?

directly related to expression of male sex characteristics and plays key role in health and well-being.

How would you administer testosterone IM?

Administer deep into gluteal muscle ○ Shake or warm vial to break up any crystals that have formed in long-acting solutions Dosage: Testosterone cypionate or enanthate (used for prolonged therapy) = 40-500 mg every 2-4 weeks

What is the primary male androgen?

Testosterone

What are some Interventions for Clomiphene Citrate?

○ Teach patients importance of taking their basal temperature 5 to 10 days following CC. ○ Discuss interconnectedness of ovulation, menstrual cycle, and sexual intercourse as related to conception. ○ Provide tips that enhance chance of fertilization, include: · positioning of a pillow under the women's hips during intercourse · elevation of the woman's hips for 30 minutes post intercourse. ○ Offer psychological support and counseling. ○ Many times multiple attempts must be made before successful conception takes place. Medication-Specific Interventions ○ Review expected outcomes of drug regimen according to HCP's prescription. ○ Teach importance of adhering to medication regimen to help minimize any adverse physical, psychological, emotional, and spiritual effects. ○ Discuss importance of contacting HCP if any visual disturbances or abdominal pains are experienced. ○ Inform patient that she will need to use caution with activities that require alertness. ○ Instruct patient that medication should be taken at same time daily. · creates steady blood levels and enhances drug effectiveness. ○ Instruct patient to notify HCP if a medication dose is missed. ○ Ensure patient understands that there is a chance of multiple births with use of CC and is aware of benefits and risks for and alternatives to this medication.

What is the MOA of testosterone?

○ Testosterone activates androgen receptors (NR3A) through: § Testosterone is transported to cytoplasm of a cell Testosterone binds to cell's androgen receptors or is reduced to DHT (DHT binds more strongly) -reactions are dependent upon specific receptors in cytoplasm Testosterone moves to nucleus of cell and affects DNA, promoting production of messenger RNA molecules □ Proteins are created and cellular tissue builds up (anabolism) □ Secondary characteristics develop: - hair growth in pubic area, face, and body -lowered voice - bigger muscles - Baldness - RBC formation -bone development

What are some side effects of Clomiphene Citrate?

○ breast discomfort ○ Fatigue ○ hot flashes ○ night sweats ○ Depression ○ Dizziness ○ Nausea ○ heavy menses compared to baseline ○ abdominal bloating ○ abdominal pain. ○ In rare cases, patients may experience dermatitis, increased appetite, urticaria, weakness, and anxiety. o CC may interfere with maturation of endometrium and cervical mucus production, thereby interfering with pregnancy.

What are some Contraindications and Drug Interactions of Clomiphene Citrate?

○ thyroid disease ○ adrenal disease ○ liver disease ○ thromboembolic disease ○ pituitary failure ○ ovarian failure ○ uterine fibroids ○ undiagnosed vag bleeding ○ Depression ○ already pregnant. o Existing ovarian cysts may enlarge when CC is taken. o does not have any known significant drug interactions o no known drug interactions between CC and human chorionic gonadotropin (hCG). o Some actions of CC may interfere with conception during luteal phase ○ this interference can be prevented by adding progesterone to a patient's medication regimen

How can testosterone be administered?

PO IV