madman
Super Moderator
Bioidentical Oral 17β-Estradiol and Progesterone for the Treatment of Moderate to Severe Vasomotor Symptoms of Menopause
Abstract
Objective: To review the efficacy, safety, and available literature regarding the novel combination bioidentical product Bijuva, or 17β-estradiol/progesterone (17β-E/P), for the treatment of moderate to severe menopausal symptoms in cisgender females with an intact uterus.
Data Sources: Literature searches of both PubMed (1966 to October 2020) and Google Scholar were conducted using search terms including bioidentical, estradiol, progesterone, menopause, E2/P4, TX-001HR, and Bijuva.
Study Selection and Data Extraction: All articles with studies conducted in cisgender human females and in the English language were considered for review; 18 publications were included.
Data Synthesis: In 1 phase 3 clinical study, 17β-E/P was proven to be effective at reducing the frequency and severity of vasomotor symptoms (VMS) at 12 weeks compared with placebo, and no cases of endometrial hyperplasia were observed over the 52-week safety study period. Menopausal women with an intact uterus were included in the study population.
Relevance to Patient Care and Practice: Concerns over the content and safety of compounded bioidentical hormones have been raised by several professional societies. As women experience VMS of menopause, a desire for a Food and Drug Administration– regulated bioidentical combination product for the treatment of moderate to severe menopausal symptoms may be desirable. Given as a once-daily oral capsule at the dose of 1 mg estradiol/100 mg progesterone, 17β-E/P is approved for the treatment of VMS associated with menopause.
Conclusions: 17β-E/P is a novel bioidentical product that is the first of its kind in the treatment of moderate to severe menopausal symptoms.
Introduction
The median age of natural menopause for cisgender women in the United States is currently 50 to 51 years, with a range of 40 to 60 years.1,2 Twelve months of amenorrhea, which is not precipitated by secondary factors, has traditionally defined clinical menopause.1 The International Society for the Study of Women’s Sexual Health and the North American Menopause Society (NAMS) introduced the term genitourinary syndrome of menopause (GSM) in 2014 to encompass the syndrome of endocrine and physical changes associated with menopause caused by estrogen loss, including atrophic vaginitis, vulvovaginal atrophy, and urogenital atrophy. It has been reported that the majority of women will experience some aspect of GSM, most often vaginal dryness or dyspareunia.3 Other GSM symptoms include physical changes involving the labia and clitoris, with additional genital symptoms such as urinary urgency and recurrent urinary tract infections.4 Although menopausal symptoms are usually most severe within 5 years of menopause onset, vulvovaginal atrophy has been found to persist for more than 6 years after menopause in some women.4 In addition to GSM, vasomotor symptoms (VMS) such as hot flashes and night sweats are experienced by 50% to 80% of menopausal women.5 Therefore, a need exists for effective treatment of menopausal symptoms whether it be short-term for VMS or longer-term for GSM.
Estradiol, estrone, and estriol are the female body’s endogenous estrogens. Estradiol is the predominant estrogen in premenopausal women, and estrone takes prevalence in menopause. As ovarian function declines leading to menopause, the serum level of estradiol continues to decrease and is predominantly responsible for the routinely reported vaginal and VMS associated with the menopausal transition.3 Menopausal symptoms may, therefore, be improved through the use of hormone therapy.
A number of treatment options are available to women depending on which bothersome symptoms of menopause are experienced.4 Nonhormonal therapies include vaginal lubricants, vaginal moisturizers, and vaginal activity and are preferred for symptoms of GSM. Prescription therapies include both local and systemic estrogen preparations. Whereas local vaginal preparations are preferred for only GSM symptoms, systemic estrogen hormone therapy at the lowest dose for the shortest amount of time is the preferred treatment of choice for VMS per the most recent recommendations.6 Estrogen formulations that are most prescribed for menopausal symptoms include conjugated equine estrogens (CEEs), synthetic conjugated estrogens, micronized 17β-estradiol, and ethinyl estradiol.6 Progestin formulations include micronized progesterone and synthetic progestins, such as medroxyprogesterone acetate (MPA), drosperinone, norethindrone, and norgestimate, and are used in combination with estrogens to prevent endometrial hyperplasia.6 Bijuva or 17β-estradiol/progesterone (17β-E/P) was approved by the Food and Drug Administration (FDA) in October 2018 for oral treatment of moderate to severe VMS secondary to menopause.7 The objective of this review is to describe the efficacy, safety, and available literature regarding the novel combination bioidentical product 17β-E/P for the treatment of moderate to severe menopausal symptoms in cisgender females with an intact uterus.
Conclusion
Although the efficacy and short-term safety is now established for a new FDA-approved, oral, fixed-dose combination, long-term safety with 17β-E/P is still unknown. 17β-E/P offers women with an intact uterus an option of a bioidentical, single-dose product that is accessible; however, the cost of the newly approved combination may be a deterrent for many patients. In line with current guidelines and recommendations for treatment of VMS, 17β-E/P may be utilized in younger women within 10 years of menopause for the shortest duration possible to avoid potential long-term risks.
Abstract
Objective: To review the efficacy, safety, and available literature regarding the novel combination bioidentical product Bijuva, or 17β-estradiol/progesterone (17β-E/P), for the treatment of moderate to severe menopausal symptoms in cisgender females with an intact uterus.
Data Sources: Literature searches of both PubMed (1966 to October 2020) and Google Scholar were conducted using search terms including bioidentical, estradiol, progesterone, menopause, E2/P4, TX-001HR, and Bijuva.
Study Selection and Data Extraction: All articles with studies conducted in cisgender human females and in the English language were considered for review; 18 publications were included.
Data Synthesis: In 1 phase 3 clinical study, 17β-E/P was proven to be effective at reducing the frequency and severity of vasomotor symptoms (VMS) at 12 weeks compared with placebo, and no cases of endometrial hyperplasia were observed over the 52-week safety study period. Menopausal women with an intact uterus were included in the study population.
Relevance to Patient Care and Practice: Concerns over the content and safety of compounded bioidentical hormones have been raised by several professional societies. As women experience VMS of menopause, a desire for a Food and Drug Administration– regulated bioidentical combination product for the treatment of moderate to severe menopausal symptoms may be desirable. Given as a once-daily oral capsule at the dose of 1 mg estradiol/100 mg progesterone, 17β-E/P is approved for the treatment of VMS associated with menopause.
Conclusions: 17β-E/P is a novel bioidentical product that is the first of its kind in the treatment of moderate to severe menopausal symptoms.
Introduction
The median age of natural menopause for cisgender women in the United States is currently 50 to 51 years, with a range of 40 to 60 years.1,2 Twelve months of amenorrhea, which is not precipitated by secondary factors, has traditionally defined clinical menopause.1 The International Society for the Study of Women’s Sexual Health and the North American Menopause Society (NAMS) introduced the term genitourinary syndrome of menopause (GSM) in 2014 to encompass the syndrome of endocrine and physical changes associated with menopause caused by estrogen loss, including atrophic vaginitis, vulvovaginal atrophy, and urogenital atrophy. It has been reported that the majority of women will experience some aspect of GSM, most often vaginal dryness or dyspareunia.3 Other GSM symptoms include physical changes involving the labia and clitoris, with additional genital symptoms such as urinary urgency and recurrent urinary tract infections.4 Although menopausal symptoms are usually most severe within 5 years of menopause onset, vulvovaginal atrophy has been found to persist for more than 6 years after menopause in some women.4 In addition to GSM, vasomotor symptoms (VMS) such as hot flashes and night sweats are experienced by 50% to 80% of menopausal women.5 Therefore, a need exists for effective treatment of menopausal symptoms whether it be short-term for VMS or longer-term for GSM.
Estradiol, estrone, and estriol are the female body’s endogenous estrogens. Estradiol is the predominant estrogen in premenopausal women, and estrone takes prevalence in menopause. As ovarian function declines leading to menopause, the serum level of estradiol continues to decrease and is predominantly responsible for the routinely reported vaginal and VMS associated with the menopausal transition.3 Menopausal symptoms may, therefore, be improved through the use of hormone therapy.
A number of treatment options are available to women depending on which bothersome symptoms of menopause are experienced.4 Nonhormonal therapies include vaginal lubricants, vaginal moisturizers, and vaginal activity and are preferred for symptoms of GSM. Prescription therapies include both local and systemic estrogen preparations. Whereas local vaginal preparations are preferred for only GSM symptoms, systemic estrogen hormone therapy at the lowest dose for the shortest amount of time is the preferred treatment of choice for VMS per the most recent recommendations.6 Estrogen formulations that are most prescribed for menopausal symptoms include conjugated equine estrogens (CEEs), synthetic conjugated estrogens, micronized 17β-estradiol, and ethinyl estradiol.6 Progestin formulations include micronized progesterone and synthetic progestins, such as medroxyprogesterone acetate (MPA), drosperinone, norethindrone, and norgestimate, and are used in combination with estrogens to prevent endometrial hyperplasia.6 Bijuva or 17β-estradiol/progesterone (17β-E/P) was approved by the Food and Drug Administration (FDA) in October 2018 for oral treatment of moderate to severe VMS secondary to menopause.7 The objective of this review is to describe the efficacy, safety, and available literature regarding the novel combination bioidentical product 17β-E/P for the treatment of moderate to severe menopausal symptoms in cisgender females with an intact uterus.
Conclusion
Although the efficacy and short-term safety is now established for a new FDA-approved, oral, fixed-dose combination, long-term safety with 17β-E/P is still unknown. 17β-E/P offers women with an intact uterus an option of a bioidentical, single-dose product that is accessible; however, the cost of the newly approved combination may be a deterrent for many patients. In line with current guidelines and recommendations for treatment of VMS, 17β-E/P may be utilized in younger women within 10 years of menopause for the shortest duration possible to avoid potential long-term risks.
