Chapter 7: Women's Health

Progestin contraindications

- Allergies - Pregnancy - Breast-feeding - History of active cardiovascular disease; thrombophlebitis; thromboembolic disorders; cerebral hemorrhage; renal disease; hepatic disease; and carcinoma of the breast, ovaries, or endometrium - Undiagnosed vaginal bleeding - A history of depression warrants caution

Drugs that decrease the effects of estrogen

- Anticonvulsants, such as carbamazepine, oxcarbazepine, phenytoin, and topiramate --Induce enzymes that accelerate the metabolism of estrogens - Barbiturates, rifampin, ritonavir, and tetracyclines --Induce enzymes that accelerate inactivation of estrogens With corticosteroids and estrogen, increased therapeutic effects and a risk of toxicity of the corticosteroids occur. Use of ropinirole with estrogen may require a dosage adjustment of the estrogen. Estrogens have a decreased effect on tamoxifen, sulfonylurea antidiabetic drugs, and anticoagulants, especially warfarin. St. John's wort increases the breakdown of estrogen, which may decrease the effectiveness of birth control pills.

Indications for use of exogenous estrogens

- As a component in birth control pills and other contraceptives. An estrogen combined with a progestin are used widely to control fertility. Estrogens are contraindicated with pregnancy. - Menopause. HCP prescribe estrogens to relieve symptoms of estrogen deficiency and to prevent / treat osteoporosis. Called estrogen replacement therapy (ERT). When prescribers order estrogen for women with an intact uterus, they also order a progestin to prevent unwanted thickening of the lining of the uterus and to decrease the risk of cancer of the uterus, a possible result of using estrogen alone. Both drug therapies are commonly referred to as HRT or menopausal hormone therapy (MHT), terms used to describe the administration of one or more female hormones during menopause. - As a replacement therapy in deficiency states, which usually result from hypofunction of the pituitary gland or the ovaries. For example, in adolescent girls with delayed sexual development, health care providers may prescribe estrogen to produce the changes that normally occur at puberty. In women of reproductive age (~12-45 years of age), prescribers may order an estrogen occasionally for menstrual disorders, including amenorrhea and abnormal uterine bleeding due to estrogen deficiency. Other uses of estrogens involve the treatment of moderate to severe vasomotor and atrophic symptoms associated with menopause, prevention of postmenopausal osteoporosis, and palliative treatment for metastatic breast carcinoma and advanced androgen-dependent prostatic cancer. Treatment of abnormal uterine bleeding caused by hormonal imbalance, in the absence of organic pathology, requires an intravenous injection. The short-term use (1-2 years) of estrogens (sometimes synthetic) in postmenopausal women may be indicated for management of menopausal symptoms. Note that the long-term use of estrogen-only therapy and estrogen-progestin combinations is no longer recommended for most women because of potentially serious adverse effects.

Estrogen-progestin combinations - contraindications

- Cigarette smoking - Age 35+ - History of thromboembolic problems - Concurrent cirrhosis or active viral hepatitis - Diabetes mellitus - Hypertension - Migraine with aura

Estrogen-progestin combinations - adverse effects

- GI: nausea and vomiting (take with food or at bedtime to minimize) - Cardiovascular effects of thromboembolism, MI, stroke, and hypertension - Gallbladder disease - Edema, weight gain, headache - Cigarette smoking increases the risk of cardiovascular adverse effects, especially in women older than 35 years of age. - Possibility of broken bones and osteoporosis, especially after menopause, from loss of stored calcium from bones with the use of Depo-Provera and Depo-SubQ Provera. There is a greater risk of bone loss with long-term use. - Risks of thromboembolic events increase with use of transdermal patch due to the higher levels of estrogen that are circulated into the blood.

Estrogen nursing implications

- Identification of those factors that result in the contraindication of estrogen use in high-risk women. Thorough medical and social history assessing for menopausal symptoms, cardiovascular disease (hypertension, hyperlipidemia, and cerebrovascular risk), gynecologic history (menstrual history, last menstrual period, and age at menopause), cancer history, and history of smoking. - Obtain a family history relating to menopause, osteoporosis, cardiovascular disease, cerebral vascular disease, and cognitive disease, as well as allergy status. - In the careful screening of any high-risk woman, the nurse assesses blood pressure, weight, height, pregnancy status, and lipid values. - A clinical breast examination with a mammogram and pelvic examination are essential.

Progestin adverse effects

- Increased risk of cardiovascular complications, such as stroke, heart attack, hypertension, thromboembolic and thrombotic disease, thrombophlebitis, retinal thrombosis, and pulmonary embolism. - Irregular vaginal bleeding (common; decreases during the first year of use). Amenorrhea may occur. - Weight gain and fluid retention (common) - Ophthalmic disorders, such as sudden, partial, or complete loss of vision - An increased risk of migraines and mental depression - Possible skin conditions, such as rash, acne, alopecia, and hirsutism - GI upset, with nausea and vomiting - Bone loss Progestins... - Should not be used in pregnancy - Should not be used in combination with estrogen for the prevention of cardiovascular disease or dementia - Are associated with an increased risk of thromboembolic events, such as myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism in women taking estrogen-progestin combination therapy - Are associated with an increased risk of dementia in postmenopausal women

Estrogen adverse effects

- Increased risk of thromboembolic conditions such as thrombophlebitis, pulmonary embolism, cerebrovascular thrombosis, and coronary thrombosis. Estrogens promote blood clotting by stimulating hepatic production of four clotting factors (II, VII, IX, X). Thromboembolic disorders are most likely to occur in women older than 35 years of age who take oral contraceptives and smoke cigarettes, postmenopausal women taking long-term estrogen and progestin therapy, and men or women who receive large doses of estrogens for cancer treatment. - Menstrual disorders: breakthrough bleeding, dysmenorrhea, and amenorrhea. - GI upset: nausea, vomiting, abdominal cramping, bloating. - Gallbladder disease. - CNS adverse reactions: migraine headache, dizziness, mental depression (caused or aggravated). - Edema and weight gain (fluid retention). Estrogens are associated with the following: - An increased risk of endometrial cancer. Estrogens should not be used alone in women with an intact uterus. - An increased risk of thromboembolic events such as myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism. Estrogens (with or without progestins) should not be used for the prevention of cardiovascular disease. - An increased risk of dementia in postmenopausal women. Estrogens should not be used for the prevention of dementia. - An increased risk of breast cancer development in women taking estrogen-progestin combinations.

Estrogen contraindications

- Known or suspected pregnancy, because teratogenic effects capable of interfering with the normal development of the fetus may result - Thromboembolic disorders, such as thrombophlebitis, deep vein thrombosis, or pulmonary embolism - Known or suspected cancers of breast or genital tissues, because the drugs may stimulate tumor growth. An exception is the use of estrogens for treatment of metastatic breast cancer in women at least 5 years postmenopause. - Undiagnosed vaginal or uterine bleeding - Fibroid tumors of the uterus - Active liver disease, including liver cancer and impaired liver function - History of cerebrovascular disease, coronary artery disease, thrombophlebitis, hypertension, or conditions predisposing to these disease processes - Tobacco use. Women who smoke cigarettes have a greater risk of thromboembolic disorders if they take estrogen supplements. Serious cardiovascular risks. The risk increases with age; thus, oral contraceptives should not be use in women over the age of 35 who smoke - Family history of breast or reproductive system cancer

Patient Teaching Guidelines for Estrogens, Progestins, and Estrogen-Progestin Combinations

- Take your weight weekly, and report sudden weight gain to your health care provider. (Such weight gain may be due to fluid retention and edema.) - Report any unusual vaginal bleeding immediately to your health care provider. - Discuss the increased thromboembolic risk associated with smoking while using estrogens or progestins. - Know the warning signs that may occur if a thromboembolism should develop—think ACHES ([severe] abdominal pain, chest pain, headache, eye changes, severe leg pain). Seek medical attention immediately if such symptoms occur. - If taking estrogen for long periods, have a physical examination at least annually. Have your blood pressure checked, as well as a breast and pelvic examination. Adverse conditions may occur when these drugs are taken for long periods. Your health care provider needs to monitor for adverse drug effects such as high blood pressure, gallbladder disease, and blood-clotting disorders. - If taking these medications for contraception, use a backup birth control method, and call your health care provider if you fail to take medications as prescribed or if an intrauterine device or a subdermal implant comes out of its own accord.

Key Concepts

- When exogenous estrogens and progestins are administered for therapeutic purposes, they produce the same effects as endogenous hormones. - Oral contraceptives are very effective at preventing pregnancy, but they do not prevent transmission of sexually transmitted diseases. - Cigarette smoking in women who use oral contraceptives increases risks of blood clots in the legs, lungs, heart, or brain. - Because estrogens cause epiphyseal closure, caution is necessary when used in children before completion of bone growth and attainment of adult height. - When estrogens are used alone in postmenopausal women, they cause endometrial hyperplasia and may cause endometrial cancer. Women with an intact uterus should also be given a progestin, which opposes the effects of estrogen on the endometrium. - The FDA has issues a black box warning that estrogens increase the risk of developing cancer of the uterus. The warning instructs women who take estrogens with or without progestins that there is an increased risk of dementia, myocardial infarctions, strokes, breast cancer, and blood clots. In addition, a black box warning warns that estrogens and progestins should not be used in pregnancy. - A black box warning outlines the concern of the use of Depo-Provera and Depo-SubQ Provera being associated with the loss of stored calcium from bones, which increases the risk of broken bones and osteoporosis, especially after menopause. There is a greater risk of bone loss with long-term use. - Black box warning regarding the risk for serious cardiovascular events from the use of oral contraceptives in women who smoke. As the risk increases with age, oral contraceptives should not be used in women over the age of 35 who smoke.

Estrogen-progestin combinations - pharmacokinetics

Absorption of ethinyl estradiol is good with oral administration, and it reaches peak plasma levels within 2 hours. It is 98% bound to plasma proteins, and its half-life varies from 6 to 20 hours. The estrogen undergoes extensive first-pass metabolism, additional metabolism, and conjugation in the liver; the conjugates are then excreted in bile and urine.

Estrogens pharmacokinetics

Conjugated estrogen and some synthetic derivatives of natural estrogens (e.g., ethinyl estradiol, the most widely used synthetic steroidal estrogen) are chemically modified to be effective with oral administration. After oral administration, these estrogens are well absorbed and are released slowly over several hours. Degradation occurs very slowly in the liver, allowing for high intrinsic potency. Ethinyl estradiol reaches peak plasma levels within 2 hours. It is 98% bound to plasma proteins, and its half-life varies from 6 to 20 hours. Extensive first-pass metabolism occurs in the liver, where further metabolism and conjugation occur; excretion of the conjugates is in bile and urine. Transdermal estradiol patches allow for absorption of estrogen through the skin to the bloodstream. The transdermal route bypasses the liver; thus, the amount of estrogen received is less. With this route, patients experience less nausea and vomiting than with the oral route. Serum levels produced through transdermal application more closely mimic premenopausal estrogen levels compared with serum levels with oral estrogens. This form of estrogen reaches peak plasma levels within 4 hours, and its half-life is approximately 4 hours.

Menstrual cycle

Consists of the follicular phase (days 1-14) and the luteal phase (days 15-28). Hormones in the hypothalamus, pituitary gland, and ovary regulate this cycle. The usual length of a complete menstrual cycle is 28 days, and the first day of menstrual bleeding is day 1.

Common reproductive health problems in women

Deficiencies in endogenous sex hormones result in the absence of normal sexual development. In women with deficiencies of these hormones, primary sex organ maturity will not occur and secondary sexual characteristics will not develop; normal growth and development of the adolescent will not occur, and reproduction is not possible. Assuming that the sexual organs and reproductive system are mature, endogenous sex hormone levels that drop after puberty will result in decreased secondary sexual characteristics. The ability to reproduce and carry a pregnancy to term is reduced. In addition, normal and aberrant changes in hormone levels across the life span can lead to conditions associated with the reproductive system. Drug therapy may be helpful. premenstrual syndrome, endometriosis, menopause

Progestin use in patients with critical illness

Due to the increased risk of thromboembolic disorders, such as thrombophlebitis, deep vein thrombosis, and pulmonary embolism associated with the use of progestins, critical illness resulting in extended bed rest may increase the risk of using the drug. It may be less beneficial.

Estrogen-progestin combinations use with hepatic impairment

Due to the metabolism of combined oral contraceptives in the liver, hepatic impairment is an absolute contraindication for use. In addition, women who have had jaundice during pregnancy have an increased risk of recurrence if they take estrogen-containing contraceptives. Any patient in whom jaundice develops when taking estrogen should stop taking the drug. Because jaundice may indicate liver damage, the cause warrants investigation.

Endometriosis

Endometriosis is one of the most common gynecologic problems in the United States, affecting an estimated 11% of women. Risk factors include family history of endometriosis, increasing age, short menstrual cycles with longer flow, young menarche, high-fat diet, and few or no pregnancies. Chronic pelvic pain is a classic symptom of endometriosis. Other characteristic indications include menorrhagia, dysmenorrhea, dyspareunia, fatigue, and abdominal pain. Infertility is also associated with endometriosis, especially in severe cases. The presence of endometrial tissue outside the uterine cavity is characteristic. This tissue can be attached to the ovaries, the fallopian tubes, the outside of the uterus, the bowels, and the retrovaginal septum. Drug Therapy - Nonsteroidal anti-inflammatory agents - Hormonal contraceptives, including a low-dose oral contraceptive and a hormonal intrauterine device - GnRH agonists - No data support one treatment or treatment combination over another. The treatment choice is based on symptom severity, response to treatment, contraceptive needs, and cost.

Estrogen use in patients with renal impairment

Estrogen use has been associated with fluid retention and dilated kidneys, especially when used in higher doses. Therefore, patients with renal impairment require close evaluation and management, and advanced impairment may be a contraindication.

Estrogens action

Estrogens circulate in the bloodstream to target cells, where they enter cells and combine with receptor proteins in cell cytoplasm. After transport of the estrogen-receptor complex to the cell nucleus, this complex interacts with DNA to produce RNA and new DNA. These substances stimulate cell reproduction and production of various proteins. Estrogen primarily influences the reproductive system, although it also affects the skeletal, metabolic, and coagulation systems, as well as the skin and subcutaneous tissues. Hormonal contraceptives that include estrogen act by several mechanisms. First, they inhibit hypothalamic secretion of GnRH, which inhibits pituitary secretion of FSH and LH. When these gonadotropic hormones are absent, ovulation and therefore conception cannot occur. Second, the drugs produce cervical mucus that resists penetration of spermatozoa into the upper reproductive tract. Third, the drugs interfere with endometrial maturation and reception of ova that are released and fertilized. These overlapping mechanisms make the drugs highly effective in preventing pregnancy.

Is the following statement True or False? Combined oral contraceptives are safe to use for all women.

False Rationale: There are several contraindications for combined oral contraceptives. These include cigarette smoking, age of 35 years and older, a history of thromboembolic problems, and concurrent cirrhosis or active viral hepatitis, diabetes mellitus, hypertension, or migraine with aura.

Estrogen and progesterone

Female sex hormones produced primarily by the ovaries and secondarily by the adrenal cortex in nonpregnant women. Small amounts of estrogens are also synthesized in the liver, kidney, brain, skeletal muscle, testes, and adipose tissue. In normal premenopausal women, estrogen synthesis in adipose tissue may be a significant source of the hormone. Women with anorexia nervosa, chronic disease, or malnutrition, as well as women who engage in long-distance running, usually have amenorrhea. As with other steroid hormones, estrogen and progesterone are synthesized from cholesterol. The ovaries and adrenal glands can manufacture cholesterol or extract it from the blood. Through a series of chemical reactions, cholesterol is converted to progesterone and then to androgens, testosterone, and androstenedione. The ovaries use these male sex hormones to produce estrogens. After formation, the hormones are secreted into the bloodstream in response to stimulation by the anterior pituitary gonadotropic hormones, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). In the bloodstream, the hormones combine with serum proteins and are transported to target tissues, where they enter body cells. They cross cell membranes easily because of their steroid structure and lipid solubility. Inside the cells, the hormones bind to estrogen or progesterone receptors and regulate intracellular protein synthesis. Estrogen can enhance target-tissue responses to progesterone by increasing progesterone receptors. Progesterone seems to inhibit tissue responses to estrogen by decreasing estrogen receptors.

Estrogen use in patients with hepatic impairment

Impaired liver function may lead to impaired estrogen metabolism, with resultant accumulation and adverse effects.

Effects of endogenous estrogens

In nonpregnant women, between puberty and menopause (permanent end of menstrual periods), estrogens are secreted in a monthly cycle called the menstrual cycle. During the first half of the cycle, before ovulation, estrogens are secreted in progressively larger amounts. During the second half of the cycle, estrogens and progesterone are secreted in increasing amounts until 2 to 3 days before the onset of menstruation. At that time, secretion of both hormones decreases abruptly. When the endometrial lining of the uterus loses its hormonal stimulation, it is discharged vaginally as menstrual flow. During pregnancy, the placenta in conjunction with the fetus produces large amounts of estrogen causing enlargement of the uterus and breasts, growth of glandular tissue in the breasts, and relaxation of ligaments and joints in the pelvis. All these changes are necessary for the growth and birth of the fetus. Finally, estrogens are deactivated in the liver and readily excreted through the kidneys. Metabolites are also formed in the gastrointestinal (GI) tract, brain, skin, and other steroid target tissues. Most of the conjugates are excreted in urine, and some are excreted in bile and recirculated to the liver or excreted in feces. Breasts Sexual organs Skeleton Skin & subcutaneous tissue Anterior pituitary gland Metabolism Blood coagulation

Estrogen-progestin combinations - patient teaching

It is essential that women seek information about the use of oral contraceptives. The nurse should be sure that women understand that oral contraceptives are very effective at preventing pregnancy but do not prevent transmission of sexually transmitted diseases (e.g., human immunodeficiency virus [HIV], Chlamydia, gonorrhea).

Estrogen-progestin combinations - nursing implications

It is necessary to assess each patient's need and desire for contraception, as well as her willingness to comply with the prescribed regimen. Assessment includes determining a patient's knowledge about birth control, both pharmacologic and nonpharmacologic, and identifying patients in whom hormonal contraceptives are contraindicated or who are at increased risk for adverse drug effects. Adherence involves the willingness to take the drugs as prescribed and to have breast and pelvic examinations and blood pressure measurements every 6 to 12 months. The goal of effective oral contraceptive use is the prevention of pregnancy with the lowest effective dose of hormones.

Estrogen-progestin combinations - assessing for adverse effects

It is very important to monitor for adverse drug effects such as high blood pressure, gallbladder disease, and blood-clotting disorders, which may be associated with oral contraceptive use. The assessment of weight, blood pressure, regularity of menses (occurring only on the withdrawal pills), absence of chest pain, abdominal pain, headache, vision changes, and leg pain indicates an absence of adverse effects of the oral contraceptives.

Progestin action

Medroxyprogesterone acetate and other progestins diffuse freely into cells, where they bind to progesterone receptors. The progestins act primarily on the endometrial lining of the uterus by changing it from a proliferative endometrium into a secretory endometrium. They also suppress the release of pituitary hormones, which inhibit ovulation. Finally, they inhibit spontaneous uterine contractions.

Menopause

Menopause is a normal physiologic response to deficiencies of endogenous sex hormones. Menopause is the absence of menses for 1 year, with the average age at 51. Because of the insufficient levels of circulating estrogen, secondary sexual characteristics diminish. As a result, there is a decrease in skin elasticity, body hair, and breast and subcutaneous tissue. The uterus and ovaries decrease in size, and the vagina becomes atrophic. Dyspareunia, urinary stress incontinence, and urinary tract infections may occur because of these hormone changes. Decreased estrogen results in vasomotor symptoms of "hot flushes" or "hot flashes," and night sweats may occur. Palpitations, headaches, and dizziness may be present. In addition, postmenopausal women may exhibit insomnia, irritability, anxiety, and depression. A reduction in the number of ovarian follicles (~100 per ovary) is the major contributing factor to menopause. Due to a reduction in the number of ovarian follicles, the secretion of inhibin B decreases, which causes an increase in FSH, and estradiol levels decrease. The hypothalamus and pituitary gland produce increased levels of GnRH, FSH, and LH in an attempt to stimulate the ovaries to produce estrogen and progesterone. The decreasing endogenous sex hormone levels result in a myriad of physical, psychological, and somatic symptoms. Long-term estrogen deficiency causes an imbalance in bone remodeling, which may lead to osteoporosis. Cardiovascular risk factors increase as total cholesterol and LDL increase and HDL decreases. Drug Therapy - Hormone replacement therapy (HRT) with estrogen is the most effective treatment available for relief of menopausal symptoms, most importantly vasomotor symptoms. The U.S. Food and Drug Administration (FDA) recommends the use of HRT only in women with symptoms severe enough to warrant its use, at the lowest dose and for the shortest duration possible, to ease the menopausal transition. - Although alternate drug therapies are available, none are as effective as estrogen. - A fixed-dose combination drug is appropriate for women who have an intact uterus who do not require a progestin.

Progestin use in patients with hepatic impairment

Metabolism of progestins occurs primarily in the liver. Therefore, impaired liver function or liver disease prohibits use.

Progestin pharmacokinetics

Oral administration of medroxyprogesterone acetate and other progestins results in rapid absorption, and the drug can reach a maximum concentration in 1 to 2 hours. During the first 6 hours, half-life is about 2 to 3 hours; thereafter, half-life extends to 8 to 9 hours. Prompt degradation occurs in the liver, and metabolites are excreted primarily in the urine. Rapid absorption is also a characteristic of intramuscular progestins, which have a half-life of just a few minutes. Long-acting forms can maintain effective concentrations for 3 to 6 months; maximum concentrations can be achieved in 24 hours with a half-life of about 10 weeks. Gel preparations have sustained-release properties, and absorption is prolonged with half-lives of 1 to 2 days.

Estrogen-progestin combinations use with critical illness

Oral contraceptive use during a critical illness that results in limited mobility is contraindicated. There is an increased risk of thromboembolic disorders, such as thrombophlebitis, deep vein thrombosis, and pulmonary embolism.

Estrogen-progestin combinations use with renal impairment

Oral contraceptives are associated with fluid retention and dilated kidneys as a result of increased renin-angiotensin-aldosterone system activity. This alteration in the renal system occurs especially when the contraceptives are used in higher doses; therefore, patients with renal impairment require close evaluation and management. Severe renal impairment may be a contraindication to oral contraceptive use.

Estrogen use in patients with critical illness

Patients should avoid taking estrogen during a critical illness that results in limited mobility. There is an increased risk of thromboembolic disorders, such as thrombophlebitis, deep vein thrombosis, and pulmonary embolism.

Estrogen use in patients receiving home care

Patients usually self-administer estrogens. Home care nurses may encounter patients or family members who take an estrogen when visiting the home for another reason. It may be necessary to teach or assist patients to take the drugs as prescribed. In addition, patients may need encouragement to keep appointments for follow-up supervision and blood pressure monitoring. In families that include postmenopausal women, home care nurses may need to teach about nonhormonal strategies for preventing osteoporosis and cardiovascular disease.

Estrogen-progestin combinations use in home care

Patients usually self-administer oral contraceptives. Home care nurses may encounter patients or family members taking one of the drugs when visiting the home for another reason. It may be necessary to teach or assist patients to take the drugs as prescribed. In addition, patients may need encouragement to keep appointments for follow-up supervision and blood pressure monitoring. When visiting families that include adolescent girls or young women, home care nurses may need to teach about birth control measures, adverse reactions, and adverse effects.

Premenstrual syndrome

Premenstrual syndrome (PMS) is characterized by physical, emotional, and behavioral symptoms that occur during the luteal phase or the last half of the menstrual cycle and resolve with menses. The term PMS is used for those women who experience these symptoms at a severe level that interferes with activities of daily living and personal relationships. Clinical manifestations include the following symptoms: - Physical: bloating, abdominal pain, headache, back pain, and breast tenderness - Emotional: agitation, irritability, anxiety, and depression - Behavioral: outbursts of anger, confusion, social withdrawal, and oversensitivity to insignificant events A more severe variant of PMS is premenstrual dysphoric disorder (PMDD). Women with PMDD experience extreme symptoms that interfere greatly with work, school, social activities, and relationships. The exact cause of PMS and PMDD is not known but is probably multifactorial. Although a hormonal abnormality has not been confirmed, evidence suggests an association with variation in the normal cyclical changes of reproductive hormones. The symptoms relate to progesterone production by the ovary. The corpus luteum produces metabolites of progesterone that bind to a neurosteroid-binding site on the gamma-aminobutyric acid (GABA) receptor. This changes the receptor, making it resistant to further activation and decreases central GABA-mediated inhibition. Neurotransmitters, particularly serotonin, are also associated with symptoms. Drug Therapy - Antidepressants have proven effective - a selective serotonin reuptake inhibitor (SSRI) or a serotonin and norepinephrine reuptake inhibitor (SNRI) may be ordered. - Oral contraceptives containing drospirenone or any progestin provide additional options but are generally considered second-line therapy. - If anxiety or insomnia are the main symptoms, a benzodiazepine such as alprazolam (Xanax) may be useful, but monitoring is necessary because drug dependency may develop.

Progesterone effects

Progesterones decrease high-density lipoprotein (HDL) cholesterol and increase low-density lipoprotein (LDL) cholesterol, both of which increase the risk of cardiovascular disease. Physiologic progesterone increases insulin levels but does not usually impair glucose tolerance. However, long-term administration of potent synthetic exogenous progestins, such as norgestrel, may decrease glucose tolerance and make diabetes mellitus more difficult to control. Like estrogen, progesterone is metabolized in the liver. In nonpregnant women, progesterone is secreted by the corpus luteum during the last half of the menstrual cycle, which occurs after ovulation. This hormone continues the changes in the endometrial lining of the uterus begun by estrogens during the first half of the menstrual cycle. These changes provide for implantation and nourishment of a fertilized ovum. When fertilization does not take place, the estrogen and progesterone levels decrease and menstruation occurs. If the ovum is fertilized, progesterone acts to maintain the pregnancy. The corpus luteum produces progesterone during the first few weeks of gestation. Then, the placenta produces the progesterone needed to maintain the endometrial lining of the uterus. In addition to its effects on the uterus, progesterone prepares the breasts for lactation by promoting development of milk-producing cells. Milk is not secreted, however, until the cells are further stimulated by prolactin from the anterior pituitary gland. Progesterone also may help maintain pregnancy by decreasing uterine contractility. This, in turn, decreases the risk of spontaneous abortion.

Progestin use in patients with renal impairment

Progestin metabolites are predominately excreted in urine. Therefore, patients with renal impairment require close evaluation and management, and advanced renal impairment may contraindicate progestin use.

Progestin - preventing interactions

Progestin use often alters liver function and endocrine function tests. It is essential that health care providers be aware that progestins are being used when laboratory testing is indicated. No reports of drug-drug, drug-food, or drug-herb interactions concerning progestin have appeared.

Progestins

Progestins are used for a range of contraceptive and noncontraceptive purposes either alone or in combination with estrogens. The choice of preparation varies with use. Provera is the prototype progestin

Progestin use

Progestins have both noncontraceptive and contraceptive uses, as part of estrogen-progestin combinations or as progestin-only preparations. Progestin-only pills are one option for women who cannot or prefer not to use estrogen-containing contraceptives. Implantable intrauterine devices (IUDs) or subdermal implants are types of long-acting reversible contraceptives. Health care providers use progestins to prevent hyperplasia of the endometrial lining of the uterus in women taking endogenous estrogen. In addition, progestins suppress ovarian function in dysmenorrhea, endometriosis, endometrial cancer, and uterine bleeding. These uses of progestins are extensions of the physiologic actions of progesterone on the neuroendocrine control of ovarian function and on the endometrium.

Estrogen-progestin combinations - interactions

Several medications may reduce the effectiveness of oral contraceptives (i.e., increase the likelihood of pregnancy). These include medications for tuberculosis and HIV as well as anticonvulsants. Patients should notify all health care providers who prescribe medications that they are taking a birth control pill. Use of an additional or alternative method of birth control is necessary (1) if a dose is missed or (2) if the oral contraceptive cannot be taken because of illness or infection. As previously mentioned, St. John's wort increases the breakdown of estrogen, which can decrease the effectiveness of birth control pills. Drugs That Decrease the Effects of Oral Contraceptives: - Anticonvulsants, such as carbamazepine, hydantoins (ethotoin, mephenytoin, phenytoin), and succinimides --Induce hepatic cytochrome P450, resulting in increased metabolism - Barbiturates such as phenobarbital, primidone, griseofulvin --Increase metabolism - Benzodiazepines, rifampin, St. John's wort --Activate the hepatic enzyme cytochrome P450, resulting in increased metabolism - Topiramate --Decreases contraceptive efficacy and increases breakthrough bleeding

Estrogen-progestin combinations - action

The estrogen component of combined oral contraceptives prevents pregnancy by inhibiting ovulation; it prevents the formation of the follicle by suppressing FSH and LH and stabilizing the endometrium. The progestin component thins the endometrium, slows sperm transport, thickens cervical mucus, and suppresses the LH surge.

Progestin nursing implications

The following information is essential in the identification of those women for whom progestin therapy is contraindicated: - Assessment of medical and social history. The nurse assesses for menopausal symptoms, cardiovascular disease (hypertension, hyperlipidemia, and cerebral vascular risk), gynecologic history (menstrual history, last menstrual period, and age at menopause), cancer history, and history of smoking. - Assessment of family history of menopause, osteoporosis, cardiovascular disease, cerebrovascular disease, cognitive disease, and allergy status - Assessment of blood pressure, weight, height, with lipid panel, clinical breast examination with age-appropriate mammogram, pelvic examination, and Pap smear

Estrogen-progestin combinations

The most effective and widely used contraceptives are estrogen-progestin combinations. For contraception, the prototype hormonal combination is Ortho-Novum. For HRT, the prototype drug is Prempro.

Estrogen-progestin combinations - use

The primary use of estrogen-progestin contraceptives is to prevent pregnancy. Four different types of hormonal contraceptives are common: monophasic contraceptives, which contain fixed amounts of both estrogen and progestin components; biphasics, which contain either fixed amounts of estrogen and varied amounts of progestin; triphasics, which contain three different doses of estrogen and progestin; and quadriphasics, which contain four different doses of estrogen and progestin.Biphasic, triphasic, and quadriphasic preparations mimic normal variations of hormone secretion, decrease the total dosage of hormones, and may decrease adverse effects. Dispensers with 28 tablets contain 7 inactive or placebo tablets of a third color. Several combination products and alternative dosage forms are available to help individualize treatment and promote adherence. Health care providers also use oral contraceptive preparations to treat menstrual disorders (e.g., amenorrhea, dysmenorrhea). The FDA has approved some oral contraceptives for the treatment of acne.

Is the following statement True or False? Estrogen and progesterone hormones are secreted during the menstrual cycle and pregnancy.

True Rationale: Estrogen and progesterone are secreted in different amounts during the menstrual cycle and during pregnancy.

Is the following statement True or False? Estrogen use should be supervised at the lowest dose for the shortest duration.

True Rationale: Estrogen use is supervised at the lowest dose for the shortest duration due to an FDA black box warning regarding estrogen use.

Progestin - patient teaching

Women who have an intact uterus should take both estrogen and progestin; the progestin component (e.g., Provera) prevents endometrial cancer, an adverse effect of estrogen-only therapy. Posthysterectomy, women should take estrogen-only medications. Combined estrogen-progestin therapy may increase blood sugar levels in women with diabetes. This effect is attributed to progestin and is unlikely to occur with estrogen-only therapy. Women with diabetes should report increased blood glucose levels. Take progestins with food or at bedtime to decrease nausea, a common adverse reaction. Patients should take their weight weekly and report sudden weight gain, which may result from fluid retention and edema. Patients should report any unusual vaginal bleeding.

Progesterone

hormone produced in the ovaries and adrenal cortex that prepares the lining of the uterus for pregnancy. Secreted during the menstrual cycle to change the endometrial lining of the uterus. Progesterone also acts to maintain pregnancy if the ovum is fertilized. Progesterone may also help maintain pregnancy by decreasing uterine contractility.

Estrogen

hormone produced primarily by the ovaries and secondarily by the adrenal cortex that promotes growth of specific body cells and development of most female secondary sexual characteristics Main function is to promote growth in tissues related to reproduction and sexual characteristics in women. Estrogens are secreted during the menstrual cycle. Estrogens are necessary during pregnancy for the growth and birth of the fetus.

Progestin

synthetic form of progesterone that is similar to the hormone produced naturally by the body most often used in combination with an estrogen in contraceptive products

Exogenous estrogens are used to...

treat women's health disorders when endogenous estrogen levels are low or absent. Conjugated estrogen (Premarin), the prototype estrogen, is the most commonly used oral estrogen.