Common Estrogens and Estrogen/Progestin Combinations Quiz

Estrogens and Progesterones

• Estrogens and progesterone are produced by the ovaries and play a crucial role in the menstrual cycle
• During the first half of the cycle, estrogens are secreted by maturing ovarian follicles, causing proliferation of the endometrium
• At midcycle, one of the ovarian follicles ruptures, forming a corpus luteum, which produces estrogens and progesterone
• The corpus luteum maintains the endometrium in a hypertrophied state until the end of the cycle
• Decreased production of ovarian hormones leads to breakdown of the endometrium and menstruation

Regulation of the Menstrual Cycle

• Two anterior pituitary hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), regulate the menstrual cycle
• FSH acts on developing ovarian follicles, causing them to mature and secrete estrogens
• LH surge at midcycle causes the dominant follicle to rupture, releasing an ovum
• LH also stimulates the corpus luteum to produce progesterone

Estrogens

• Estrogens are produced by the ovaries and are responsible for the growth and maturation of the female reproductive tract
• Estrogens also direct pigmentation of the nipples and genitalia
• During the follicular phase, estrogens promote ductal growth in the breast, thickening of the vaginal epithelium, and proliferation of the uterine epithelium
• Estrogens also increase vaginal acidity and stimulate uterine blood flow and growth

Physiologic Effects of Estrogens

• Estrogens have a positive effect on bone by blocking bone resorption and promoting mineral deposition
• Estrogens lower cardiovascular risk by decreasing vasoconstriction and raising HDL
• Estrogens promote blood coagulation and have a neuroprotective effect
• Estrogens preserve cognitive function, enhance short-term memory, and regulate mood

Therapeutic Uses of Estrogens

• Estrogens are used for menopausal hormone therapy (HT), female hypogonadism, and acne
• Estrogens are also used for cancer palliation and gender affirmation therapy for transgender women

Adverse Effects of Estrogens

• Estrogens can cause endometrial hyperplasia, endometrial cancer, breast cancer, and cardiovascular thromboembolic events
• Estrogens are contraindicated in patients with a history of deep vein thrombosis, pulmonary embolus, or liver disease

Progesterone

• Progesterone is produced by the ovaries and placenta
• Progesterone is synthesized by the corpus luteum in response to LH
• Progesterone production by the corpus luteum ceases if implantation of a fertilized ovum does not occur

Therapeutic Uses of Progesterone

• Progesterone is used for HT, dysfunctional uterine bleeding, amenorrhea, and endometrial hyperplasia and carcinoma
• Progesterone is also used to support early pregnancy in women undergoing IVF and to prevent preterm birth

Adverse Effects of Progesterone

• Progesterone can cause breast tenderness, headache, abdominal discomfort, arthralgias, and depression

Hormone Therapy (HT)

• HT consists of low doses of estrogen (with or without a progestin) taken to compensate for the loss of estrogen during menopause

• HT is used to control menopausal symptoms, including vasomotor symptoms, sleep disturbances, and improved cognition and mood

• The risks of HT, including breast cancer and thromboembolic events, must be weighed against its benefits### Hormone Therapy (HT) for Menopause

• HT has three approved indications: treatment of vasomotor symptoms, genitourinary syndrome, and prevention of postmenopausal osteoporosis.

• Duration of treatment is relatively short for vasomotor symptoms and genitourinary syndrome (typically 3 to 4 years), but lifelong for prevention of osteoporosis.

• HT is the most effective treatment for vasomotor symptoms, and the lowest effective dosage should be used to increase safety.

Alternatives to HT

• Two antidepressants, escitalopram and desvenlafaxine, can reduce hot flashes.
• Other options, such as clonidine and pregabalin, have also shown some success.
• Soy isoflavones and black cohosh are not effective in reducing hot flashes.

Genitourinary Syndrome of Menopause

• HT is the most effective treatment for genitourinary syndrome, characterized by dryness, irritation, and uncomfortable intercourse.
• Topical estrogen formulations, such as vaginal creams and rings, are safer than oral estrogen and can be used to manage vulvar and vaginal symptoms.

Postmenopausal Osteoporosis

• HT reduces bone loss and decreases the risk of osteoporosis and related fractures.
• However, when HT is stopped, bone mass rapidly decreases, and alternative treatments are preferred.

Inappropriate Uses of HT

• HT is not recommended for cardiovascular disease or dementia.
• Discontinuation of HT may cause vasomotor symptoms to return, and no firm guidelines exist for stopping HT.

Estrogen and Progestin Therapy

• Estrogen and progestin are commonly administered continuously, but an alternative is to give estrogen continuously and give progestin cyclically.
• Vaginal estrogens can be given continuously for 1 to 2 weeks, followed by dosing 1 to 3 times per week.

Transgender Hormonal Therapy

• Transgender women require medication to decrease testosterone levels and estrogen to promote female characteristics.
• Management is highly individualized, and monitoring of therapy must include the effects of estrogen and antiandrogens.
• Risks of HT are the same as for nontransgender patients.

Female Sexual Interest/Arousal Disorder (FSIAD)

• FSIAD is a common problem in women, especially after menopause.
• Treatment options include off-label use of drugs such as sildenafil and testosterone, and newly approved drugs such as flibanserin and bremelanotide.

Birth Control

• Several factors should be considered when choosing a method of birth control, including effectiveness, safety, and personal preference.
• The most effective methods are etonogestrel subdermal implants, intramuscular medroxyprogesterone acetate, sterilization, and IUDs.
• Combination oral contraceptives (OCs) are effective, but their effectiveness is impacted by factors such as weight and smoking.

Contraceptive Methods

• OCs reduce fertility primarily by inhibiting ovulation.
• Combination OCs employ three estrogens: ethinyl estradiol, mestranol, and estradiol valerate.
• Progestins in OCs can be grouped into four generations, with differences in side effects and efficacy.
• OCs can have a wide range of adverse effects, including nausea, menstrual irregularity, and thromboembolic disorders.

Oral Contraceptives (OCs)

• OCs are available in monophasic, biphasic, and triphasic formulations, with different levels of estrogen and progestin.

• OCs can decrease the risk of several disorders, including ovarian cancer, endometrial cancer, and acne.

• OCs can interact with other drugs, including warfarin, hypoglycemic agents, and theophylline.

• Some OCs contain levomefolate, a metabolite of folic acid, to reduce the risk of fetal neural tube defects.### Combination Oral Contraceptives (OCs)

• Most OCs are taken in a repeating sequence of 21 days of active pills followed by 7 days of inactive pills or iron-containing pills.

• The sequence can be started on the first day of the menstrual cycle or the first Sunday after the onset of menses.

• With a Sunday start, backup contraception is recommended for the first 7 days.

• Each dose should be taken at the same time every day to maintain effectiveness.

Extended or Continuous Cycle OCs

• 14 products are packaged and marketed for prolonged use, decreasing episodes of withdrawal bleeding and associated symptoms.
• Successive dosing cycles should commence every 28 days, even if there is breakthrough bleeding or spotting.

Missed Doses

• If one or more pills are missed in the first week, take one pill as soon as possible and continue with the pack, using an additional form of contraception for 7 days.
• If one or two pills are missed during the second or third week, take one pill as soon as possible and continue with the active pills, skipping the placebo pills and starting a new pack once all active pills have been taken.
• If three or more pills are missed during the second or third week, follow the same instructions as above, using an additional form of contraception for 7 days.

Progestin-Only OCs (Minipills)

• Contain a progestin but no estrogen, making them safer than combination OCs but less effective.
• Alter cervical secretions, making them thicker and stickier, and modify the endometrium, making it less favorable for implantation.
• Taking the pill at the same time every day is crucial, as missing a dose by even 3 hours can reduce efficacy.
• Backup contraception is recommended if unprotected sexual intercourse occurs.

Transdermal Contraceptive Patch

• Has the same mechanism as combination OCs, but with a more convenient dosing schedule (once a week).
• Has the same contraceptive efficacy and incidence of breakthrough bleeding and spotting as combination OCs.
• Adverse effects include breast discomfort, headache, local irritation, nausea, and menstrual cramps.

NuvaRing

• A hormonal contraceptive device designed for vaginal insertion, containing an estrogen/progestin combination.
• Prevents pregnancy by suppressing ovulation.
• Adverse effects, drug interactions, warnings, and contraindications are the same as for combination OCs.
• Insertion is done by the user, and a new ring is inserted after a ring-free week.

Nexplanon

• A single 4-cm rod containing 68 mg of etonogestrel, a synthetic progestin, implanted subdermally in the arm.
• Provides contraception for 3 years, with recent studies showing effectiveness up to 5 years.
• Bleeding episodes are irregular and unpredictable, and bleeding irregularities are the leading reason for discontinuation.
• Safe to use during breastfeeding after the 21st postpartum day.

Depot Medroxyprogesterone Acetate (DMPA)

• Given by injection intramuscularly or subcutaneously, protecting against pregnancy for 3 months or longer.
• Inhibits the secretion of gonadotropins, thereby inhibiting follicular maturation and ovulation, thickening cervical mucus, and causing thinning of the endometrium.
• Adverse effects include menstrual disturbances, mild weight gain, abdominal bloating, headache, depression, and decreased libido.
• Poses a risk for reversible bone loss, but this risk does not outweigh the benefits of treatment.

Intrauterine Devices (IUDs)

• Among the most reliable forms of reversible birth control, with two main classes: hormone-free copper IUDs and levonorgestrel-containing IUDs.
• Can cause cramping and alteration of menses, with main side effects including heavier menstrual bleeding and cramping for copper IUDs, and bleeding irregularities for levonorgestrel-containing IUDs.

Spermicides

• Chemical surfactants that kill sperm by destroying their cell membranes, available in various formulations.
• When used alone, spermicides are only moderately effective, but combined use with a diaphragm or condom increases efficacy.
• Adverse effects include vaginal irritation and dryness.

Emergency Contraception (EC)

• Defined as contraception implemented after intercourse, with safe and effective methods available for decades.
• Can be accomplished in two basic ways: taking an emergency contraceptive pill (ECP) or inserting a copper-T IUD.
• Three progestin-only products are available: Plan B One-Step, Next Choice One Dose, and Next Choice, which contain levonorgestrel.
• Ulipristal acetate is another ECP that prevents conception primarily by suppressing ovulation.

Test your knowledge of common oral and transdermal estrogens like conjugated equine estrogens, estradiol, and estropipate, as well as estrogen/progestin combinations such as conjugated equine estrogens/medroxyprogesterone acetate and estradiol/norethindrone acetate.