Demystifying Bioidentical Hormones A Review Of BHRT Use In Clinical Practice With Respect To Menopausal Concerns

This article provides an overview of the scientific literature regarding the safety and efficacy of bioidentical hormone replacement therapy (BHRT) for the treatment of symptoms associated with menopause, including vasomotor symptoms, urinary tract infections, and vaginal atrophy. This review specifically compares safety of bioidentical estrogens and progesterone to conventional hormone replacement therapy (HRT). Data from large randomized controlled trials such as the Women’s Health Initiative (WHI) and the Heart and Estrogen/progestin Replacement Study (HERS) demonstrate detrimental effects resulting from use of estrogen in combination with synthetic progestins. In contrast, data from the large E3N cohort suggest that bioidentical progesterone may offset this risk. Progesterone differs from synthetic progestins in its biological effects on breast tissue, metabolic parameters, as well as on the cardiovascular system. In addition, different routes of BHRT delivery will be discussed, comparing topical and transdermal application methods with oral administration. Demystifying Bioidentical Hormones A Review Of BHRT Use In Clinical Practice With Respect To Menopausal Concerns By Tannaz Mokhtari, BSc, ND and Ishita Patel, HBSc, Pharm D, RPh Tannaz Mokhtari, BSc, ND and Ishita Patel, HBSc, Pharm D, RPh Hayyan HealthCare , 9301 Bathurst St. Unit 8, Richmond Hill, On L4C 3T7 tannaz@yournd.com February / March 2014 l www.ihpmagazine. com 65 Introduction Bioidentical hormones are manufactured to be molecularly identical to endogenous human hormones. They are derived primarily from plant sources, such as soy and wild Mexican yam root. The extracted plant compounds then undergo synthetic processing to obtain structures identical to endogenous human hormones (Bosarge 2009). Some examples include estriol, estradiol, estrone, progesterone and testosterone. There are many commercially available, FDA-approved bioidentical hormones in various forms and dosages. The following products are available: in pill form, Estrace or Innofem; vaginal cream for vaginal symptoms such as Estrace; patches Menopause RM.indd 56 14-02-18 9:35 AM 66 www.ihpmagazine. com l February / March 2014 such as Alora, Climara, Estraderm; topical gels Estrogel/Elestrin; and ring forms Estring and Fermin. Progesterone forms include in pill form Prometrium, and as vaginal gel Crinone 4%. Combined formulations include: Combipatch (Estradiol and norethindrone acetate), Prefest (pill) and Limara Pro (patch). By contrast, synthetic hormones differ structurally compared to human hormones. These compounds typically contain a chemically conjugated functional group to prevent the breakdown of the hormone before it reaches the circulation (Bosarge 2009). Examples include conjugated equine estrogen (CEE) or Premarin, and medroxyprogesterone acetate (MPA). The following diagrams show the molecular structure of biological estrogens and progesterone, compared to the synthetic forms that are used in conventional HRT and are sometimes referred to as “natural hormones”. The bioidentical hormones have a molecular structure identical to the biological hormones. Rationale for HRT The use of hormones in the treatment of periand postmenopausal symptoms has a long history dating from the 1960s. Hormone replacement therapy (HRT) is often prescribed to treat symptoms associated with menopause, including hot flashes, sleep disturbance and night sweats (Schmidt 2006). However, since the publication of the Women’s Health Initiative Study (WHI) reporting an increased risk of various cardiovascular events and cancers, many women suffering from periand postmenopausal symptoms have turned to the use of BHRT. BHRT is perceived as an effective and safer alternative to conventional treatment with synthetic hormones. Before menopause, ovarian follicles are the source of greater than 90% of estrogen, particularly estradiol. During pregnancy, estriol is the most active form of estrogen. After menopause, the conversion of androstendione to estrone by non-ovarian tissues is the main source of estrogen. Relief of hot flashes in postmenopausal women can usually be achieved by maintaining serum estradiol levels at 40-50 pg/ml, the lowest level of estradiol that is expected to be seen in a typical menstrual cycle (Schmidt 2006). Co-administration of a progestogen is still the standard method used in order to prevent estrogen-induced endometrial hyperplasia (Emons 2004), but co-administration of a synthetic progestin has its own side effects. Estrogen receptor subtypes The conflicting results regarding the safety of estrogen use may be in part due to the different forms of estrogen. Each form exhibits different binding affinity and selectivity to estrogen receptors, which is responsible for mediating a different physiologic effect. Estrogenic effects are mediated through two different estrogen receptor subtypes: estrogen receptor-alpha (ER-a) and estrogen receptorbeta (ER). ER-a promotes breast cell proliferation, while ERinhibits proliferation and prevents breast cancer development via G2 cells cycle arrest (Holtorf 2009). Estradiol equally activates ER-a and ER, while estrone selectively activates ER-a at a ratio of 5:1. In contrast, estriol selectively binds ERat a ratio of 3:1(Holtorf 2009). This suggests that estriol is strongly implicated in breast cancer prevention, while the other forms of estrogens may play a role in breast cancer promotion (Holtorf 2009). Due to minimal (<0.4%) conversion of intravenously administered estradiol or estrone to estriol, given its protective qualities, estriol is physiologically important in postmenopausal women. Therefore it is advisable to coadminister estriol with estradiol (Schmidt 2006). The synthetic counterpart of endogenous estrogens, CEE (Premarin), also selectively binds ER. Its components are potent downregulators of the ERreceptor Figure 1. Structure of biological hormones (Left column) compared to synthetics used in conventional hormone replacement therapy (Right column) B