2.5 mg
5 mg
10 mg

Dehydroepiandrosterone (DHEA) is a synthetic steroid that is chemically identical to the naturally-occurring pro-hormone 5-dehydroepiandrosterone (5-DHEA), a pro-hormone secreted by the adrenal cortex, gonads and brain tissue. The intravaginal DHEA insert is indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. The product provides a non-estrogen, vaginal therapy option to address isolated genitourinary symptoms in these women. DHEA was shown to significantly (p less than 0.05) reduce the severity of pain experienced during sexual intercourse when compared to placebo in two 12-week placebo-controlled clinical trials of 406 healthy postmenopausal women 40 to 80 years of age.

The mechanism of action of prasterone in postmenopausal women with vulvar and vaginal atrophy is not fully established. Prasterone is a synthetic steroid that is chemically identical to the naturally-occurring pro-hormone 5-dehydroepiandrosterone (5-DHEA), a pro-hormone secreted by the adrenal cortex, gonads and brain tissue. Exogenous prasterone is converted into active estrogens in the same manner as endogenous prasterone or DHEA. Endogenous DHEA is synthesized by the conversion of cholesterol via CYP11A1 to pregnenolone, followed by CYP17 conversion to DHEA and then to DHEAS via dehydroepiandrosterone sulfatransferase. The synthesis of DHEA occurs exclusively in the adrenal cortex in women. In females, DHEA serum levels are high in neonates right after birth, rapidly fall within 5 months, then begin to rise at the age of 7 years. Endogenous DHEA concentration then peaks again in females at roughly the 20th and 40th year of life. DHEA levels decline steadily after the fifth decade.

DHEA is administered intravaginally. Exogenous DHEA is metabolized in the same manner as endogenous DHEA. Human steroidogenic enzymes such as hydroxysteroid dehydrogenases, 5-alpha-reductases, and aromatases transform DHEA into androgens and estrogens.

Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: Data not available.

Route-Specific Pharmacokinetics

In a clinical study, administration of DHEA vaginal insert once daily for 7 days resulted in a mean DHEA Cmax and exposure (AUC 0 to 24) at Day 7 of 4.4 ng/mL and 56.2 ng x hour/mL, respectively, which were significantly higher than those in the group treated with placebo. The Cmax and AUC of the metabolites testosterone and estradiol were also slightly higher in women treated with DHEA compared to those receiving placebo.

DHEA is contraindicated for use in patients with vaginal bleeding or dysfunctional uterine bleeding of undetermined origin. DHEA is metabolized to estrogen; DHEA use is contraindicated in known or suspected estrogen-dependent neoplasia, such as breast cancer, ovarian cancer, or endometrial cancer. DHEA has not been adequately studied in women with breast cancer; therefore, it should not be used in women with known or suspected breast cancer or with a history of breast cancer. Unopposed estrogen therapy increases the risk of endometrial cancer in women with a uterus. Prolonged use is associated with an increased risk of neoplasm with a risk persisting for at least 8 to 15 years after estrogen therapy is discontinued. Adding a progestin to postmenopausal estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Of note, estrogen-progestin regimens carry their own unique risks compared to estrogen-alone regimens. Progestin use with DHEA has not be evaluated.
DHEA is only indicated in postmenopausal women. There are no data with DHEA use in pregnancy regarding any drug-associated risks. Animal reproduction studies have not been conducted with DHEA. Studies of the role of endogenous fetal and maternal DHEA (DHEA) in pregnancy indicate that the ratio of DHEA or DHEAS to other hormones in the serum or placenta may influence the processes of fetal development, parturition, and labor. Endogenous DHEA and DHEAS appear to be important in the functional development of the adrenal cortex and other endocrine activities in the fetus; it is assumed that exogenous DHEA supplementation to a pregnant woman could potentially have deleterious effects on fetal development or viability. The androgenic effects of DHEA could potentially result in masculinization of a female fetus. Do not administer DHEA to a pregnant woman.
DHEA is only indicated in postmenopausal women. There is no information on the presence of DHEA in human milk, the effects on the breastfed infant, or the effects on milk production. Most hormones are excreted in breast milk. Like other androgenic hormones, it is possible that DHEA could inhibit lactation. Due to the potential harm to a nursing infant, DHEA use should be avoided during breast-feeding.
DHEA is only indicated for use in menopausal and postmenopausal females, and is not indicated in infants, children, or adolescents. Safety and effectiveness have not been established in pediatric patients.

DHEA is only indicated in postmenopausal women. There are no data with DHEA use in pregnancy regarding any drug-associated risks. Animal reproduction studies have not been conducted with DHEA. Studies of the role of endogenous fetal and maternal DHEA (DHEA) in pregnancy indicate that the ratio of DHEA or DHEAS to other hormones in the serum or placenta may influence the processes of fetal development, parturition, and labor. Endogenous DHEA and DHEAS appear to be important in the functional development of the adrenal cortex and other endocrine activities in the fetus; it is assumed that exogenous DHEA supplementation to a pregnant woman could potentially have deleterious effects on fetal development or viability. The androgenic effects of DHEA could potentially result in masculinization of a female fetus. Do not administer DHEA to a pregnant woman.

DHEA is only indicated in postmenopausal women. There is no information on the presence of DHEA in human milk, the effects on the breastfed infant, or the effects on milk production. Most hormones are excreted in breast milk. Like other androgenic hormones, it is possible that DHEA could inhibit lactation. Due to the potential harm to a nursing infant, DHEA use should be avoided during breast-feeding.

Vaginal discharge is the most frequently reported adverse reaction with DHEA, with an incidence of greater than or equal to 2%. In four 4 placebo-controlled, 12-week clinical trials, there were 38 cases in 665 women (5.71%) treated with DHEA compared to 17 cases in 464 (3.66%) in the placebo treatment group. In a 52-week non-comparative clinical trial, vaginal discharge and abnormal pap smear were the most frequently reported adverse reactions in women receiving DHEA with an incidence of greater than or equal to 2%. There were 74 cases of vaginal discharge (14.2%) and 11 cases of abnormal pap smear (2.1%) in 521 participating postmenopausal women. Cases of abnormal pap smear include 1 case of low-grade squamous intraepithelial lesion (LSIL) and 10 cases of atypical cells of undetermined significance (ASCUS).

Store this medication in its original container at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.

North Florida	South Florida
Jacksonville	Miami	West Palm Beach	Weston
Pensacola	Hialeah	Pompano Beach	Delray Beach
Tallahassee	Fort Lauderdale	Davie	Homestead
Ocala	Port St. Lucie	Miami Beach	Tamarac
Gainesville	Pembroke Pines	Plantation	Sarasota
Fort Walton Beach	Hollywood	Sunrise	Wellington
Panama City	Miramar	Boca Raton	Jupiter
Palm Coast	Coral Springs	Deerfield Beach	Margate
Dunnellon	Miami Gardens	Boynton Beach	Coconut Creek
	Naples	Lauderhill	Broward
	Spring hill	Orlando

• Intrarosa (prasterone) vaginal insert package insert. Quebec City, Canada: Endoceutics Inc.; 2018 Feb.
• Kroboth PD, Slalek FS, Pittenger AL et al. DHEA and DHEA-S: a review. J Clin Pharmacol 1999;39:327-348.