36.2 Hormonal, Contraception, and Infertility Drugs

Estrogens

Estrogen is produced in the body in four types: estrone (E1), estradiol (E2), estriol (E3), and estetrol (E4) (Hariri & Rehman, 2023). Indications for the use of estrogen include hormone replacement therapy (HRT) during menopause to relieve signs and symptoms such as vaginal dryness, hot flashes, mood swings, and painful intercourse. One type of estrogen, estradiol, can also be used as HRT for hypogonadism and ovarian failure (medical or physiological). Estradiol is available in a multitude of types and combinations, and dosages vary with the indication and use, the administration method, and its combined form (DailyMed, Estradiol, 2021; Hariri & Rahman, 2023).

Estrogens are administered in several ways. If administered orally, they are absorbed well from the gastrointestinal tract, metabolized by the liver, and excreted in urine. Depending on the dose, estrogens can inhibit or promote ovulation. Other positive effects include preservation of calcium and phosphorus and stimulation of bone growth.

Table 36.1 lists two forms of estrogen therapy that are synthetic but identical to the body’s natural hormone and typical routes and dosing for adult clients.

Adverse Effects and Contraindications

Adverse effects of estrogens are related mostly to the retention of fluids. Migraine headaches, bloating, weight gain, mood depression, stroke, and cardiovascular disease are known adverse reactions and can be life-threatening.

Contraindications for estrogens include hormone-positive breast cancer, undiagnosed uterine bleeding, and active or history of thrombophlebitis or thromboembolism. Pregnancy and breastfeeding are also contraindications because estrogens cross the placenta and enter breast milk. Estrogens must be used cautiously in conditions that are affected or exacerbated by fluid retention, such as migraine headaches with an aura, renal or cardiac dysfunction, and hypertension. Obesity and age greater than 35 are circumstances when estrogens should be used cautiously, if at all.

Table 36.2 is a drug prototype table for estrogens featuring conjugated estrogen. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.

Progestins

Progestins include progesterone and its derivatives. They can function as both a stimulant and an inhibitor to manage the secretion of pituitary gonadotropins. One of the properties of progestins is their ability to prevent follicular maturation and ovulation. They accomplish this by inhibiting the secretion of pituitary gonadotropins and decreasing LH secretion. Progestins thicken cervical mucus, which hinders sperm migration and changes the endometrium to decrease the likelihood that an egg can be implanted. These properties make progestins an excellent contraceptive medication. Progestins are metabolized by the liver and excreted in urine.

Progesterone is used for several reasons. It can be added to estrogen in postmenopausal HRT to reduce the risk of endometrial cancer. It is also used for amenorrhea and for dysfunctional uterine bleeding. It can be administered orally, intramuscularly, intrauterine, and as a gel, depending on the intended effect of the drug. Progesterone dosage for HRT varies, as does the number of days it is used per month.

Desogestrel, drospirenone, medroxyprogesterone, norethindrone, and levonorgestrel are progestins. Desogestrel and drospirenone are used only in combination form for contraception.

Table 36.3 lists common progestins and typical routes and dosing for adult clients.

Adverse Effects and Contraindications

Adverse effects, contraindications, and precautions for progesterone are similar to those of estrogen and include weight gain, nausea, bloating, headaches, visual disturbances, rash, and acne. Contraindications for progestin are hypersensitivity, pregnancy/lactation, history of thrombotic events, sexually transmitted disease (STD), pelvic inflammatory disease, endometriosis, undiagnosed uterine bleeding, cardiac/renal/liver disease, and hormone-sensitive cancers. Caution should be used with clients who have any condition that can be affected by fluid retention (migraine headache, cardiac/renal disease, seizure disorder), diabetes, hyperlipidemia, or clinical depression.

Table 36.4 is a drug prototype table for progestins featuring norethindrone. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.

Oral and Injectable Contraceptives

Oral contraceptives are pills that contain either a combination of estrogen and progestin or progestin alone. Oral contraceptives are prescribed based on a client’s medical history, needs, and risk factors. Combined oral contraceptives (COCs) contain estrogen and progestin in varying dosages. The type of progestin varies with each COC depending on the individual client’s needs and medical status. There are three different categories of COCs. Monophasic contraceptive pills contain a fixed ratio of estrogen and progestin. Biphasic COCs contain a fixed dose of estrogen with a varying dose of progestin. Triphasic COCs contain low doses of both estrogen and progestin with a varying dose of estrogen (Britton et al., 2020; Casey, 2022; Mayo Clinic, 2023a; Cooper et al., 2020).

Injectable contraceptives are hormones that are injected, usually intramuscularly, at specific intervals to provide the same birth control protection as oral contraceptives (Britton et al., 2020; Casey, 2022; Cooper et al., 2020).

Table 36.5 lists common forms of COCs and typical routes and dosing for adult clients.

Progestin-only contraceptives are used when estrogen is not appropriate for the client’s situation. For instance, the client may have significant risk factors such as obesity, smoking, hypertension, and age over 35 years. These are also commonly used by clients who are breastfeeding, as they have less effect on the breast milk supply than oral contraceptives containing estrogen. Medroxyprogesterone, norethindrone, and levonorgestrel are progestin-only contraceptives. The injectable contraceptive medroxyprogesterone is administered intramuscularly or subcutaneously (Britton et al., 2020; Casey, 2022; Cooper et al., 2020).

Table 36.6 lists common progestin-only contraceptives and typical routes and dosing for adult clients.

Intrauterine and Implanted Contraceptives

In addition to oral and injectable contraceptives, intrauterine devices (IUDs) and implanted contraceptive devices are available. The advantages to these forms of contraception are their long-term effects and ease of use. They do not require remembering to take daily pills or scheduling appointments for injections. However, they do have side effects, like any hormonal medication. Additionally, because they are inserted into the body, risks of infection and migration (moving) or dislodgement of the devices exist (Andersen & Spanfeller, 2022; Britton et al., 2020; Casey, 2022; Madden, 2023).

IUDs have become the most commonly used contraceptive method in the world and are among the most effective types of contraceptives. IUDs are small T-shaped devices that are placed inside the uterus via the cervix. Five types of IUDs are used in the United States. Four of them are hormonal. They release small amounts of progestin (levonorgestrel) into the body. They also have a positive effect of making monthly periods lighter. Further, these IUDs may decrease the risk of ovarian, endometrial, and cervical cancers (Andersen & Spanfeller, 2022; Casey, 2022; Madden, 2023).

The fifth type is copper. It works by stimulating the body’s immune response, creating an unfavorable uterine environment for the sperm, and preventing pregnancy. It may initially increase bleeding with periods and between periods; however, the bleeding should lessen to an acceptable level. Hormonal IUDs can last for 3–8 years, depending on the specific hormone and dose, and the copper type lasts for 10 years (Andersen & Spanfeller, 2022; Britton et al., 2020; Casey, 2022; Madden, 2023).

Another type of birth control method is the implanted device. The device comes as a single soft, radiopaque, flexible implant (4 cm in length × 2 mm in diameter) that contains 68 mg etonogestrel, 15 mg barium sulfate, and 0.1 mg magnesium stearate. It comes with the insertion device in the package. The contraceptive is implanted under the skin of the inner upper arm. It has the same action, use, contraindications, and side effects as any other contraceptive containing levonorgestrel. The primary risk is infection or dislodgement of the implant. This device lasts for 3 years and is a highly effective contraceptive method (Britton et al., 2020; Casey, 2022; DailyMed, Nexplanon, 2022).

Table 36.7 lists the four hormonal IUD types and dosing for adult clients.

Adverse Effects and Contraindications

Contraindications include active STI or recent pelvic infection, pregnancy, cancer of the cervix or uterus, or unexplained vaginal bleeding. Hormonal IUDs should not be used by clients who have had breast cancer.

Side effects include bleeding and spotting as the uterus adjusts to the IUD. Other adverse effects include abdominal pain, endometriosis, pelvic inflammatory disease (PID), and expulsion of the IUD. Extremely rare is the possibility that an IUD may cause uterine perforation.

For a copper IUD, the bleeding and spotting may last up to 6 months. The insertion of the IUD may be uncomfortable, and the client may experience some cramping and backache for a day or two after the procedure. The pain can be managed using ibuprofen or acetaminophen and heating pads. Other side effects include nausea, cramping, ovarian cysts, and mood changes. The most concerning complications of all IUDs are infection, expulsion, or perforation; however, the risk for these complications is extremely low (Andersen & Spanfeller, 2022; Britton et al., 2020; Casey, 2022; Madden, 2023).

Other Contraceptive Methods

Two other hormonal contraceptive methods are a transdermal patch and a vaginal ring. The patch contains an estrogen–progestin combination and is applied weekly for 3 weeks and left off for 1 week. The vaginal ring also contains a combination of estrogen–progestin and is inserted once and left in place for 3 weeks. The ring is removed for 1 week before a new ring is inserted. Both methods are based on a 4-week cycle (Britton et al., 2020; Casey, 2022).

In 2018 the FDA approved a new vaginal ring that is reused for a year (Center for Devices and Radiological Health, 2018). It is used according to the same cycle of 3 weeks in place and 1 week out. The difference is that between cycles it can be washed and stored and then reused.

Specific client teaching for the vaginal ring includes properly placing and removing the ring and properly disposing of the monthly ring or cleaning and storage of the yearly ring. If the ring is removed for more than 3 hours, clients should be advised to use a backup contraceptive method concurrently for 7 days (Britton et al., 2020; Casey, 2022).

Client teaching for the patch includes correct opening of the package; placing the patch on clean, dry skin on the buttocks, upper outer arm, lower abdomen, or upper body; pressing it firmly for 10 seconds; and not placing the patch on the breasts (Britton et al., 2020; Casey, 2022).

All contraceptive drugs, regardless of form, are derived from the hormones estrogen and progestin. Refer to Table 36.1 and Table 36.3 for information related to mechanism of action, indication, therapeutic effects, side effects, contraindications, and food and drug interactions.

Initiating Contraceptives

The oral and transdermal methods can be initiated using a first-day start method, a quick start method, or a Sunday start method. All are equally effective. The first-day start method means the client starts the contraceptive on day 1 of their menstrual cycle and continues as directed. The quick start method means that the client starts the contraceptive immediately, regardless of the timing of their menstrual period. This is week one. The individual continues to take the pills or apply the patch as directed. One advantage of the quick start method is that the client can begin taking the medication the day they receive the medication. The Sunday start method means the client will start using the contraceptive on the first Sunday following the start date of their period. Then the client continues to take the pills or apply the patch as directed. A disadvantage of the Sunday start method is that clients may forget to start on the correct date and then must wait until after their next period to begin taking the medication (Britton et al., 2020; Casey, 2022; Cooper et al., 2020).

Adverse Effects and Contraindications

Adverse effects of infertility drugs include a significant risk of multiple births and birth defects. Ovarian overstimulation is another side effect that is manifested by abdominal pain, distention, ascites (fluid accumulation in the abdomen), and pleural effusion. Headache, fluid retention, ovarian enlargement, uterine bleeding, nausea, and fever are additional side effects.

Infertility drugs are contraindicated when the client has primary ovarian failure, thyroid or adrenal dysfunction, ovarian cysts, or idiopathic uterine bleeding or is pregnant. Clients with respiratory issues or who are breastfeeding should use caution before deciding to take fertility medications.

Table 36.10 is a drug prototype table for infertility drugs featuring clomiphene. Clomiphene is a selective estrogen receptor modulator (SERM) with both estrogen antagonist and agonist effects that increase gonadotropin release as well as increase production of FSH and LS. The ultimate effect is ovarian follicular growth (Carson & Kallen, 2021). The table lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.