Femlyv (Millicent), an orally disintegrating tablet containing ethinyl estradiol and norethindrone acetate, has been approved by the FDA for prevention of pregnancy in females with a body mass index (BMI) ≤35 kg/m². It is the first hormonal contraceptive to become available in an orally disintegrating tablet formulation. Traditional oral and chewable tablets containing ethinyl estradiol and norethindrone acetate in a wide range of doses, including those found in Femlyv, have been available in the US for years.

The primary symptoms of menopause are genitourinary and vasomotor. The genitourinary syndrome of menopause (GSM) includes symptoms such as burning, irritation, dryness, dyspareunia, dysuria, and recurrent urinary tract infection. Vasomotor symptoms (VMS; hot flashes, night sweats) often disrupt sleep.

The FDA has approved Opill (Perrigo), a progestin-only oral contraceptive that contains norgestrel, for sale over the counter (OTC). Opill is the first oral contraceptive to be approved in the US for sale without a prescription. Approval of OTC Opill is intended to increase access to effective contraception and reduce the rate of unintended pregnancies.

Intrauterine devices (IUDs) and the etonogestrel implant are the most effective reversible contraceptive methods available. Hormonal oral contraceptives, patches, rings, and injectables are also effective in preventing pregnancy. When used alone, barrier and behavioral methods generally have higher failure rates than other methods (see Table 1). Selection of a contraceptive method is usually based on patient-specific factors and personal preference

Myfembree (Myovant/Pfizer), an oral fixed-dose combination of the gonadotropin-releasing hormone (GnRH) receptor antagonist relugolix, the estrogen estradiol, and the progestin norethindrone acetate, has been approved by the FDA for management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women. It is the second product to be approved in the US for this indication; Oriahnn, which contains the GnRH receptor antagonist elagolix in combination with estradiol and norethindrone acetate, was approved earlier. Relugolix was approved for treatment of advanced prostate cancer as Orgovyx in 2020.

Oriahnn (Abbvie), a fixed-dose combination of the gonadotropin-releasing hormone (GnRH) receptor antagonist elagolix, the estrogen estradiol, and the progestin norethindrone acetate copackaged with elagolix alone, has been approved by the FDA for oral treatment of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women. It is the first product to be approved in the US for this indication. Elagolix (Orilissa) has been available since 2018 for treatment of moderate to severe pain associated with endometriosis. The GnRH receptor antagonist relugolix (Orgovyx), which is approved for treatment of advanced prostate cancer, is being reviewed by the FDA for use in combination with estradiol and norethindrone acetate for the same indication as Oriahnn.

The FDA has approved Twirla (Agile Therapeutics), a transdermal contraceptive patch containing the estrogen ethinyl estradiol and the progestin levonorgestrel, for use in women with a BMI <30 kg/m². It is the second contraceptive patch to become available in the US; Xulane, a patch that delivers ethinyl estradiol and the progestin norelgestromin, has been available since 2014.

The FDA has approved Phexxi (Evofem), a nonhormonal prescription-only vaginal gel containing lactic acid, citric acid, and potassium bitartrate, for prevention of pregnancy. The gel is intended for on-demand contraception; it is not effective when used after intercourse. It was previously approved for use as a vaginal lubricant (Amphora), but was never marketed.

The primary symptoms of menopause are genitourinary (genitourinary syndrome of menopause; GSM) and vasomotor (VMS). Vulvovaginal atrophy can cause vaginal burning, irritation and dryness, dyspareunia, and dysuria, and increase the risk of urinary tract infections. Vasomotor symptoms ("hot flashes") cause daytime discomfort and night sweats that may disrupt sleep. Hormone therapy is the most effective treatment for both genitourinary and vasomotor symptoms.

The FDA has approved a progestin-only oral contraceptive ("minipill") containing drospirenone (Slynd – Exeltis). All other progestin-only oral contraceptives available in the US contain norethindrone (Camila, and others). Progestin-only oral contraceptives are similar in efficacy to combination oral contraceptives. They are used predominantly by breastfeeding women and by those in whom estrogen is poorly tolerated or contraindicated. Combination oral contraceptives containing drospirenone and ethinyl estradiol have been available for years.

Annovera (TherapeuticsMD), a contraceptive vaginal ring that releases segesterone acetate, a synthetic progestin, and ethinyl estradiol, was approved by the FDA in 2018 and is now available. It is the first product to contain segesterone and the second vaginal ring to become available in the US; NuvaRing, which delivers etonogestrel and ethinyl estradiol, was the first. Unlike NuvaRing, which requires use of a new ring each month, the Annovera ring can be used for an entire year, but it must be removed for one week each month.

In our article on Bijuva, the oral fixed-dose combination of estradiol and progesterone (Med Lett Drugs Ther 2019; 61:99), Table 1 should have included single-ingredient oral formulations of estradiol and progesterone (see below). They will be added to the table as it appears online, along with medroxyprogesterone (Provera, and generics), another single-ingredient progestin available for use in women with an intact uterus who take systemic estrogen for menopausal symptoms. Taking generic estradiol and progesterone separately may be less convenient than taking Bijuva, but they cost less and allow for more dosing flexibility.

The FDA has approved Bijuva (TherapeuticsMD), a fixed-dose combination of estradiol and progesterone, for oral treatment of moderate to severe vasomotor symptoms (hot flashes) due to menopause in women with an intact uterus. The manufacturer is marketing Bijuva as "the first and only FDA-approved combination of bio-identical estradiol and bio-identical progesterone in a single daily oral capsule".

Intrauterine devices (IUDs) and the etonogestrel implant are the most effective reversible contraceptive methods available. Hormonal oral contraceptives, patches, rings, and injectables are also highly effective in preventing pregnancy. When used alone, barrier and fertility-based methods generally have higher failure rates than other methods.

The FDA has approved the steroid prasterone (Intrarosa – Endoceutics) for intravaginal treatment of postmenopausal women with moderate-to-severe dyspareunia due to vulvovaginal atrophy (VVA). Also called dehydroepiandrosterone (DHEA), prasterone is produced in the adrenal glands, gonads, and brain and converted intracellularly into active metabolites of estrogens and androgens. DHEA has been available over the counter for years as an oral dietary supplement claimed to benefit sexual, cardiovascular, and neuropsychiatric dysfunction.

The FDA has approved Kyleena (Bayer), an intrauterine device (IUD) that releases the synthetic progestin levonorgestrel, for prevention of pregnancy. It is the fourth levonorgestrel-releasing IUD to be approved in the US. Like Mirena, which has been available since 2000, Kyleena is approved for up to 5 years of use.

The primary symptoms of menopause are genitourinary and vasomotor. A thin, dry vaginal lining and thin urethral mucosa can cause vaginal and vulvar burning and irritation, pain during intercourse, and an increased risk of urinary tract infections. Vasomotor symptoms ("hot flashes") cause daytime discomfort and night sweats that may disrupt sleep.

Implants, intrauterine devices (IUDs), and sterilization are the most effective contraceptive methods available. Pills, patches, rings, and injectables, when used correctly, are also highly effective in preventing pregnancy. Barrier and fertility-based methods have the highest rates of failure.

The FDA has approved Duavee (Pfizer), a fixed-dose combination of conjugated estrogens and the new selective estrogen receptor modulator (SERM) bazedoxifene, for treatment of moderate to severe vasomotor symptoms and for prevention of osteoporosis in postmenopausal women with an intact uterus. Bazedoxifene is an estrogen agonist/antagonist with estrogen-like effects on bone and antiestrogen effects on the uterus. It is the second SERM to be approved for prevention of osteoporosis; raloxifene (Evista, and generics) has been available as a single agent for this indication since 1997.

Some readers have objected to our recommendation (Med Lett Drugs Ther 2013; 55:55) that postmenopausal women with an intact uterus who take the oral estrogen agonist/antagonist ospemifene (Osphena) to reduce the severity of dyspareunia should also take a progestin.1 Ospemifene has agonistic effects on the endometrium, and the Osphena package insert says: "Generally, when a product with estrogen agonistic effects on the endometrium is prescribed for a postmenopausal woman with a uterus, a progestin should be considered to reduce the risk of endometrial cancer."

Endometrial hyperplasia has been reported in more than 20% of women taking unopposed systemic estrogen for more than one year; the risk is closely related to the dose and duration of treatment. Adding a progestin to estrogen therapy in women with a uterus reduces the risk of endometrial hyperplasia and cancer, but has been associated with an increased risk of invasive breast cancer and thromboembolic events.2

In ospemifene clinical trials, the drug was taken without a progestin and at 1 year there were no cases of endometrial hyperplasia or carcinoma, but only a small number of women took the drug for more than 12 weeks. These studies excluded women with an endometrial thickness of ≥4 mm detected by transvaginal ultrasound, pathological findings on endometrial biopsy or Pap test, or any other clinically significant gynecological abnormality. They also excluded women who were obese or had hypertension, among many other exclusions.

It is possible that the estrogenic effects of ospemifene on the endometrium will prove to be similar to those of the estrogen agonist/antagonist raloxifene (Evista), which has not increased the incidence of endometrial cancer.3 For now, it would not be unreasonable for postmenopausal women with an intact uterus who can be followed closely for vaginal bleeding or spotting and do not have risk factors for endometrial cancer (obesity, hypertension, diabetes, nulliparity) to take ospemifene without a progestin. For all others, a progestin should be considered.

1. Ospemifene (Osphena) for dyspareunia. Med Lett Drugs Ther 2013; 55:55.

2. JE Manson et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA 2013; 310:1353.

3. SR Goldstein. Postmenopausal dyspareunia: has the Food and Drug Administration really helped? Menopause 2013; 20:596.

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The FDA has approved Quartette (Teva), an extended-cycle combination oral contraceptive containing increasing doses of the estrogen ethinyl estradiol (EE) combined with the progestin levonorgestrel (LNG). The rationale is that a gradual increase in the EE dose may reduce unscheduled bleeding or spotting, a common adverse effect of extended-cycle oral contraceptives.

The primary symptoms of menopause are vasomotor and genitourinary. Vasomotor symptoms ("hot flashes") cause daytime discomfort and chronic insomnia. A thin, dry vaginal lining and thin urethral mucosa can cause vaginal and vulvar irritation, pain during intercourse, and an increased risk for urinary tract infection.

Osteoporosis is characterized by low bone mass with microarchitectural disruption and skeletal fragility that results in an increased risk of fracture. The diagnosis has traditionally been established by bone densitometry, which is generally reported in terms of standard deviations (SD) from mean values in young adults (T-score). The World Health Organization (WHO) has defined normal bone mineral density (BMD) for women as a value within one SD of the young adult mean. Values 2.5 SD or more below the mean (T score -2.5) are defined as osteoporosis. The WHO has developed a computerized model (FRAX) that predicts the 10-year probability of a hip fracture or any other major osteoporotic fracture based on clinical risk factors and BMD at the femoral neck.

The FDA recently approved the marketing of hydroxyprogesterone caproate injection (Makena – Ther-Rx) for prevention of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth.

Sexual complaints related to desire, arousal, orgasm and painful intercourse are common in women. Since the last Medical Letter article on this subject, some new information has become available.

The choice of which contraceptive to use may vary from one stage of reproductive life to another. Intrauterine devices (IUDs), progestin implants and sterilization are the most effective contraceptive methods available to women. Hormonal contraceptives, when used correctly, are also highly effective in preventing pregnancy. Barrier and fertility-based methods have the highest rate of failure.

The FDA has approved the marketing of Natazia (Bayer), a 4-phase oral contraceptive containing the estrogen estradiol valerate and the progestin dienogest, both used for the first time in the US for this indication.

Combination oral contraceptives increase the risk of venous thromboembolism (VTE). Their benefits, in addition to preventing pregnancy, include lowering the risk of ovarian and endometrial cancer, reducing dysfunctional uterine bleeding and increasing serum hemoglobin concentrations. Are these benefits worth the risk? And are some combination oral contraceptives safer than others?

An old conjugated estrogens vaginal cream (Premarin Vaginal Cream - Wyeth) has been newly approved by the FDA specifically for treatment of moderate to severe dyspareunia due to vulvar and vaginal atrophy associated with menopause. Synthetic conjugated estrogens A vaginal cream (Barr) has also been approved for this indication, but has not yet been marketed.

Osteoporosis is characterized by low bone mass with microarchitectural disruption and skeletal fragility that results in an increased risk of fracture. The diagnosis has traditionally been established by bone densitometry, which is generally reported in terms of standard deviations (SD) from mean values in young adults (T score). The World Health Organization (WHO) has defined normal bone mineral density (BMD) for women as a value within one SD of the young adult mean. Values 2.5 SD (T score -2.5) or more below the mean are defined as osteoporosis. The WHO has developed a computerized model (FRAX) that predicts the 10-year probability of hip fracture based on clinical risk factors and BMD at the femoral neck.

Transdermal, transvaginal and intrauterine hormone delivery systems have made highly effective contraceptive products more convenient to use. New oral contraceptive options include regimens with fewer or shorter hormone-free intervals.

Three low-dose transdermal estrogens were recently approved by the FDA for treatment of menopausal vasomotor symptoms. Elestrin and Divigel are transdermal estradiol gels and Evamist is an estradiol spray. Elestrin has been marketed in Europe since 1976.

A combination tablet containing estradiol and drospirenone (Angeliq - Berlex) recently became available for treatment of moderate to severe menopausal symptoms in women with an intact uterus. Since the last Medical Letter issue reviewing such devices,1 more continuous glucose monitoring (CGM) systems have become available. Five devices available now, and two expected to be marketed soon, are listed in the table on page 14. The FDA has approved continuous glucose devices only for the observation of glucose trends.

Many drugs are now marketed for treatment of postmenopausal osteoporosis, but questions remain about their use.

The pathogenesis of acne is multifactorial: follicular hyperkeratinization, Propionibacterium acnes bacteria, sebum production, androgens and inflammation have all been implicated. P. acnes, a gram-positive microaerophilic bacterium, plays an important role in the development of acne lesions by secreting chemotactic factors that attract leukocytes to the follicle, causing inflammation.

Estrogen is the most effective treatment for menopausal vasomotor symptoms (hot flashes), but the Women's Health Initiative study found that women who took estrogen plus a progestin for more than 5 years were at increased risk for myocardial infarction, stroke, pulmonary emboli, deep vein thrombosis, breast cancer, and possibly dementia. Are there effective alternatives?

The FDA has approved a new low-dose estrogen patch (Menostar - Berlex) for prevention of osteoporosis in postmenopausal women. Unlike other estrogen patches, it is not approved for treatment of hot flashes or other menopausal symptoms. Promotional material from the manufacturer suggests that this low dose of estrogen could prevent osteoporosis without some of the adverse effects of higher doses.

In recent years, several new contraceptive options have become available in the United States. Novel hormone delivery systems such as transdermal, transvaginal and intrauterine devices have improved the convenience of highly effective contraceptive products. Like oral contraceptives and most barrier contraceptives, these devices do not protect against sexually transmitted diseases.

Seasonale (Barr), the first "extended-cycle" oral contraceptive, is now available in the US for pregnancy prevention. Active tablets containing 30 ╡g of ethinyl estradiol and 0.15 mg of levonorgestrel are taken for 84 consecutive days, followed by 7 days of inactive tablets, allowing for withdrawal bleeding only four times a year. Other combination oral contraceptives are dispensed as 21 days of active tablets and 7 days of placebo or no tablets, resulting in 13 withdrawal bleeding episodes each year.

An FDA Advisory Committee has recommended over-the-counter (OTC) marketing of Plan B (Barr), an emergency contraceptive "pill pack" that contains two 0.75-mg tablets of levonorgestrel to be taken 12 hours apart (Medical Letter 2000; 42:10). Plan B is one of two FDA-approved products for this indication. The Preven Emergency Contraceptive Kit (Medical Letter, 40:102, 1998) includes four tablets, each containing 0.25 mg of levonorgestrel and 50 ╡g of ethinyl estradiol; these are taken 2 at a time 12 hours apart (the "Yuzpe regimen") and are available only by prescription.

Many drugs are now marketed for treatment of post-menopausal osteoporosis (PD Delmas, Lancet 2002; 359:2018). Prevention of this disorder has been complicated by the news that hormone replacement therapy (HRT), which many women have been taking to prevent osteoporosis, increases the incidence of coronary heart disease and that of breast cancer, stroke and pulmonary embolism as well (Medical Letter 2002; 44:78).

The results of a large randomized controlled trial of estrogen plus a progestin to prevent heart disease in postmenopausal women were recently reported (Writing Group for the Women's Health Initiative Investigators, JAMA 2002; 288:321).

An oral contraceptive (Yasmin - Berlex) containing 3 mg of drospirenone and 30 mcg of ethinyl estradiol is being promoted as having a low incidence of adverse effects.

A transdermal contraceptive patch (Ortho Evra — Ortho-McNeil) has been approved by the FDA. Each 20 cm² patch contains 6 mg of the progestin norelgestromin (the active metabolite of norgestimate) and 0.75 mg of ethinyl estradiol.

The FDA had approved an intrauterine contraceptive device that releases the synthetic progestin levonorgestrel over a period of five years. The device has been available in Europe for 10 years.

Two types of oral contraceptives are available in the USA: combination oral contraceptives that contain both an estrogen and a progestin, and progestin-only contraceptives, or "mini-pills."Used as directed, all oral contraceptives marketed in the USA are similarly effective in preventing pregnancy.

The FDA has approved marketing of Plan B (Women's Capital Corporation), an emergency contraceptive "pill pack"that contains two 0.75-mg tablets of levonorgestrel.

The US Food and Drug Administration (FDA) has approved two new retinoids for treatment of psoriasis. Tazarotene gel 0.05% and 0.1% (Tazorac - Allergan) is being marketed for topical use in patients with stable, mild to moderate plaque psoriasis. Acitretin (Soriatane - Roche) is being promoted for systemic use in severe psoriasis.

Anastrozole (Arimidex - Zeneca), a selective nonsteroidal aromatase inhibitor, has been approved by the US Food and Drug Administration (FDA) for treatment of postmenopausal women with advanced breast cancer that has progressed during treatment with tamoxifen (Nolvadex, and others).

Desogen (Organon) and Ortho-Cept (Ortho), two oral contraceptives each containing a low dose (30 mcg) of the estrogen ethinyl estradiol plus 150 mcg of the progestin desogestrel, were recently approved by the US Food and Drug Administration for marketing in the USA. They are the first US oral contraceptives to contain desogestrel, which is widely used in oral contraceptive combination products in other countries. Desogestrel is one of three new progestins (norgestimate and gestodene are the others) considered less androgenic than previously available progestins (L Speroff et al, Obstet Gynecol, 81:1034, June 1993).

The commonly used methods of reversible contraception are listed in the table below. Additional information is available in RA Hatcher et al, Contraceptive Technology, 1990-1992, 15th ed, New York:Irvington, 1990.

The bone mass of an average person reaches a maximum at the age of 25 to 30, stays the same for about 15 years, and then progressively declines at a rate of 0.2% to 0.5% per year. At menopause, women go through a period of increased bone resorption (2% per year) for about 10 years and then resume a gradual rate of bone loss. Current strategies for prevention and treatment of Postmenopausal Osteoporosis include increasing calcium intake to maximize peak bone mass, using antiresorptive drugs to decrease postmenopausal resorption, and using other drugs to stimulate bone systhesis (BL Riggs and LJ Melton, III, N Engl J Med, 327:620, Aug 27, 1992).