Drugs Affecting the Female Reproductive System

Smoke

Women taking estrogen should be advised to avoid this lifestyle behavior because it can cause increased risk of thrombotic events?

Sex Hormones

Drugs: estrogens and progestins

Estrogens

• estradiol (Estrace, Climara, and others)

• conjugated estrogens (Premarin), esterified estrogen (Menest)

• estropipate (Ogen).

Progestins

• drospirenone (Yasmin, Yaz)

• etonogestrel (Implanon),

• levonorgestrel (Mirena)

• medroxyprogesterone (Provera)

• norethindrone (Aygestin)

• norgestrel (generic)

• progesterone (Prometrium, and others),

• desogestrel

• ulipristal (Ella)

Estrogens

• in small doses, they are used for hormone replacement therapy (HRT) when ovarian activity is blocked or absent.

• treat female hypogonadism and ovarian failure

• prevent postpartum breast engorgement, as part of combination contraceptives

• to slow bone loss in osteoporosis, and for palliation in certain cancers that have known receptor sensitivity

menopause

An absence or decrease in estrogen produces the signs and symptoms of ________ in the uterus, vagina, breasts, and cervix.

Effects of Estrogen

• Growth of genitalia (in preparation for childbirth)

• Growth of breast tissue (in preparation for pregnancy and lactation)

• Characteristic female pubic hair distribution (a triangle)

• Stimulation of protein-building (important for the developing fetus)

• Increased total blood cholesterol (for energy for the mother as well as the developing fetus) with an increase in high-density lipoprotein levels (“good” cholesterol, which serves to protect the female blood vessels against atherosclerosis)

• Retention of sodium and water (to provide cooling for the heat generated by the developing fetus and to increase diffusion of sodium and water to the fetus through the placenta)

• Inhibition of calcium resorption from the bones (helps deposit calcium in the fetal bone structure; when this property is lost at menopause, osteoporosis, or loss of calcium from the bone, is common)

• Alteration of pelvic bone structure to a wider and flaring pelvis (to promote easier delivery)

• Closure of the epiphyses (to conserve energy for the fetus by halting growth of the mother)

• Increased thyroid hormone globulin (metabolism needs to be increased greatly during pregnancy, and the increase in thyroid hormone facilitates this)

• Increased elastic tissue of the skin (to allow for the tremendous stretch of the abdominal skin during pregnancy)

• Increased vascularity of the skin (to allow for radiation loss of heat generated by the developing fetus)

• Increased uterine motility (estrogen is high when the ovum first leaves the ovary, and increased uterine motility helps move the ovum toward the uterus and to propel the sperm toward the ovum)

• Thin, clear cervical mucus (allows easy penetration of the sperm into the uterus as ovulation occurs; used in fertility programs as an indication that ovulation will soon occur)

• Proliferative endometrium (to prepare the lining of the uterus for implantation with the fertilized egg)

• Anti-insulin effect with increased glucose levels (to allow increased diffusion of glucose to the developing fetus)

• T-cell inhibition (to protect the non self-cells of the embryo from the immune surveillance of the mother)

Effects of Progesterone

• Decreased uterine motility (to provide increased chance that implantation can occur)

• Development of a secretory endometrium (to provide glucose and a rich blood supply for the developing placenta and embryo)

• Thickened cervical mucus (to protect the developing embryo and keep out bacteria and other pathogens; this is lost at the beginning of labor as the mucous plug)

• Breast growth (to prepare for lactation)

• Increased body temperature (a direct hypothalamic response to progesterone, which stimulates metabolism and promotes activities for the developing embryo; this increase in temperature is monitored in the “rhythm method” of birth control to indicate that ovulation has occurred)

• Increased appetite (this is a direct effect on the satiety centers of the hypothalamus and results in increased nutrients for the developing embryo)

• Depressed T-cell function (again, this protects the nonself-cells of the developing embryo from the immune system)

• Anti-insulin effect (to generate a higher blood glucose concentration to allow rapid diffusion of glucose to the developing embryo)

Progestins

• used as contraceptives, most effectively in combination with estrogens

• treat primary and secondary amenorrhea and functional uterine bleeding and as part of fertility programs.

• some are useful in treating specific cancers with specific receptor site sensitivity

3 years

Etonogestrel (a Progestins) is a subdermal implant that may be left in place for up to how many years before it must be removed.

Estrogens

contraindicated in:

• allergies

• in patients with idiopathic vaginal bleeding, breast cancer, or any estrogen-dependent cancer (all of which could be exacerbated by the drug)

• a history of thromboembolic disorders, including cerebrovascular accident, or with heavy smokers because of the increased risk of thrombus and embolus development

• With hepatic dysfunction, because of the effects on liver function.

• In pregnancy

Caution in:

• patients with metabolic bone disease because of the bone-conserving effect of

  estrogen

• renal insufficiency: fluid and electrolyte imbalance

• Hepatic impairment

Progestins

contraindicated in:

• presence of pelvic inflammatory disease (PID)

• sexually transmitted diseases

• endometriosis

• pelvic surgery

• Drospirenone: in patients who are at risk for hyperkalemia due to renal disorders, liver disease, adrenal dysfunction, or the use of other drugs that can affect potassium levels because of its antimineralocorticoid effects and the risk of hyperkalemia.

Caution in:

• patients with epilepsy,

• migraine headaches

• asthma

• cardiac or renal dysfunction

Estrogens

Adverse Effects:

• genitourinary (GU) tract

  • breakthrough bleeding

  • menstrual irregularities

  • dysmenorrhea

  • amenorrhea

  • changes in libido.

• Systemic Effects:

  • fluid retention

  • electrolyte disturbances

  • headache

  • dizziness

  • mental changes

  • weight changes

  • edema.

• GI effects:

  • nausea,

  • vomiting

  • abdominal cramps

  • bloating

  • colitis.

  • acute pancreatitis

  • cholestatic jaundice

  • hepatic adenoma

Progestins

Adverse effects

Vaginal Gel 

• headache

• nervousness

• constipation

• breast enlargement

• perineal pain.

Intrauterine systems

• abdominal pain

• intensifying endometriosis symptoms

• abortion

• PID

• Expulsion of the intrauterine device.

Estrogens

Drug–Drug Interactions:

• Increased therapeutic and toxic effects of corticosteroids

• St. John’s wort can affect this drugs metabolism, contraceptives containing this drug would become less effective

Progestins

Drug–Drug Interactions:

• Interaction with barbiturates, carbamazepine, phenytoin, griseofulvin, penicillins, tetracyclines, or rifampin may reduce this drugs effectiveness

• Patients using any of these drugs should use another method of contraception if birth control is needed.

• St. John’s wort can affect the drug’s metabolism, contraceptives containing this drug would become less effective

Estrogen Receptor Modulators

Drugs:

Raloxifene (Evista) 

Toremifene (Fareston).

Estrogen Receptor Modulators

Are not hormones but affect specific estrogen receptor sites, stimulating some and blocking others.

• Are developed to produce some of the positive effects of estrogen replacement while limiting the adverse effects

Estrogen Receptor Modulators

Contraindications and Cautions:

• known allergy to the drug

• pregnancy and lactating mothers

• patients with a history of venous thrombosis or smoking because: increased risk of blood clot formation if they are combined.

Estrogen Receptor Modulators

Adverse Effects:

• GI upset (nausea, vomiting)

• Changes in fluid balance

  • headache, dizziness, visual changes, and mental changes.

• Secondary

  • Hot flashes, skin rash, edema, and vaginal bleeding

• Venous thromboembolism

Estrogen Receptor Modulators

Drug–Drug Interactions:

• Cholestyramine reduces the absorption of raloxifene.

• Highly protein-bound drugs, such as diazepam (Valium), ibuprofen (Motrin), indomethacin (Indocin), and naproxen (Naprosyn), may interfere with binding sites.

• Warfarin taken with raloxifene may decrease the prothrombin time

Fertility Drugs

cetrorelix (Cetrotide)

chorionic gonadotropin (Pregnyl)

chorionic gonadotropin alpha (Ovidrel)

clomiphene (Clomid and others)

follitropin alfa (Gonal-F)

follitropin beta (Follistim AQ)

ganirelix (generic)

menotropins (Pergonal)

urofollitropin (Bravelle).

Fertility Drugs

These drugs are used to treat infertility in women with functioning ovaries whose partners are fertile.

• Women without primary ovarian failure who cannot get pregnant after 1 year of trying may be candidates for the use of fertility drugs.

Fertility Drugs

A drug that work either directly to stimulate follicles and ovulation or stimulate the hypothalamus to increase FSH and LH levels, leading to ovarian follicular development and maturation of ova.

(they only work to stimulate functioning ovaries)

Cetrorelix

inhibits premature LH surges in women undergoing controlled ovarian stimulation by acting as a GnRH antagonist.

Menotropins

A purified gonadotropin (similar to FSH and LH), that is also used to stimulate spermatogenesis

Fertility Drugs

Contraindications and Cautions:

• presence of primary ovarian failure

• thyroid or adrenal dysfunction: effects on the hypothalamic–pituitary axis

• ovarian cysts: can become larger

• Pregnancy and lactating mother

• idiopathic uterine bleeding

• known allergy to any fertility drug to avoid hypersensitivity reactions

• thromboembolic diseases: increased thrombus formation

• women with respiratory diseases

Fertility Drugs

Adverse Effects:

• greatly increased risk of multiple births and birth defects

• ovarian overstimulation (abdominal pain, distention, ascites, pleural effusion)

• headache

• fluid retention

• nausea

• bloating

• uterine bleeding

• ovarian enlargement

• gynecomastia

• febrile reactions

Uterine Motility Drugs

Drugs that stimulate uterine contractions to assist labor or induce abortion

Tocolytics

Are drugs used to slow uterine activity

• Terbutaline, a beta2-selective adrenergic agonist (widely used off-label)

• black box warning

hydroxyprogesterone caproate (Makena)

The drug that was approved to reduce the risk of preterm birth in women with a single-fetus pregnancy and a history of singleton spontaneous preterm birth.

• not approved for use in multiple-fetus pregnancies

Oxytocics

Drugs that stimulate contraction of the uterus, much like the action of the hypothalamic hormone oxytocin, which is stored in the posterior pituitary.

Oxytocics

Methylergonovine (Methergine)

Oxytocin (Pitocin).

Oxytocics

These drugs directly affect neuroreceptor sites to stimulate contraction of the uterus. They are especially effective in the gravid uterus.

• Indicated

  • prevention and treatment of uterine atony after delivery

  • This is important to prevent postpartum hemorrhage.

Oxytocics

Contraindications and Cautions:

• presence of any known allergy

• cephalopelvic disproportion

• unfavorable fetal position

• complete uterine atony

• early pregnancy

• compromised by uterine stimulation.

• coronary disease and hypertension: causes

• patients who have had previous cesarean births

• arterial contraction

• Hepatic or renal impairement

Oxytocics

Adverse Effects:

• Common: GI upset, nausea, headache, and dizziness also are common

• Methylergonovine: ergotism

• manifested by nausea, blood pressure changes, weak pulse, dyspnea, chest pain, numbness and coldness in extremities, confusion, excitement, delirium, convulsions, and even coma.

• severe water intoxication: coma patients

• maternal death: used in prolonged period.

Abortifacients

Drugs that are sed to evacuate uterine contents via intense uterine contractions.

Abortifacients

carboprost (Hemabate)

dinoprostone (Cervidil, Prepidil Gel, Prostin E2)

mifepristone (RU-486, Mifeprex)

Abortifacients

stimulate uterine activity, dislodging any implanted trophoblasts and preventing implantation of any fertilized egg.

12 - 20 weeks

Abortifacients is only approved to terminate pregnancy at how many week from the date of the last menstrual period

Abortifacients

Contraindications and Cautions:

• known allergy to the drug or prostaglandins

• after 20 weeks from the last menstrual period: too late for an abortion

• Active PID or acute CV, hepatic, renal, or pulmonary disease

• Lactating mother’s

• history of asthma, hypertension, or adrenal disease

• Acute vaginitis or scarred uterus

Abortifacients

Adverse Effects:

• Exaggeration of the desire effect: 

  • abdominal cramping, heavy uterine bleeding, perforated uterus, and uterine rupture

• headache

• nausea

• vomiting

• diarrhea

• diaphoresis (sweating)

• backache, and rash

Misoprostol (Cytotec)

A Oxytocics (Uterotonic Agent) that is a synthetic prostaglandin E1 analogue that binds uterine prostaglandin receptors to cause cervical ripening, uterine smooth muscle contraction, increased uterine tone, provides Postpartum hemorrhage (PPH) control 

Tocolytics

Labor suppressants, they delay preterm labor.  

Tocolytics

• Terbutaline

• Nifedipine

• Magnesium Sulfate

Magnesium Sulfate

a physiological calcium antagonist used in obstetrics for short-term tocolysis, seizure prophylaxis/treatment in preeclampsia/eclampsia, and fetal neuroprotection in imminent very-preterm birth.

Calcium gluconate

An intravenous (and oral) calcium salt used to raise serum calcium acutely or provide cardioprotective calcium in specific toxic or emergency settings.

• Antidote for Magnesium sulfate toxicity

Progestin-only pills

A hormonal contraceptive that safe in breastfeeding; must be taken at the same time daily.

Rho(D) Immune Globulin (RhoGAM)

Prevents Rh isoimmunization in Rh-negative mothers with Rh-positive fetus/baby.

• When administered to an Rh-negative mother, it destroys any Rh-positive fetal RBCs that enter her bloodstream. This prevents her immune system from developing anti-Rh antibodies, which could otherwise attack Rh-positive fetal cells in future pregnancies (causing hemolytic disease of the newborn).

28 weeks gestation, within 72 hours postpartum if baby is confirmed Rh positive or after any risk event

What is Rho(D) Immune Globulin (RhoGAM) standard timing of administration?

• antepartum and postpartum

Combined oral contraceptives COCs

The most common type of combined hormonal contraceptives (CHCs) that contain an estrogen and a progestin

• Contraindicated: > 35 smoker, HTN, clotting history