Life Extension Magazine October 2009
Why Are They Still Controversial?
Bioidentical Progesterone vs. non-bioidentical Progestin for the Treatment of Menopausal Symptoms
Four head-to-head studies comparing bioidentical progesterone to non-bioidentical progestin reported that women experienced greater satisfaction, improved quality of life, and fewer side effects when they were switched from non-bioidentical progestin to bioidentical progesterone.
In a landmark study, researchers at the Mayo Clinic studied 176 menopausal women receiving hormone replacement therapy. All of these women had previously taken hormone replacement therapy with non-bioidentical progestin, but were switched at a later date to bioidentical progesterone. The findings across the board showed that women had substantially greater improvement in their symptoms when using bioidentical progesterone, compared to non-bioidentical progestin. Sixty-five percent of the women believed that HRT combined with bioidentical progesterone was better than HRT combined with non-bioidentical progestin. The beneficial effects of bioidentical progesterone compared to non-bioidentical progestin included a 30% reduction in sleep problems, a 50% reduction in anxiety, a 60% reduction in depression, a 25% reduction in menstrual bleeding, a 40% reduction in cognitive difficulties, and a 30% improvement in sexual function. Eighty percent of women in the study reported overall satisfaction with the bioidentical progesterone formulation.152 The results of this study provide evidence of the superiority of bioidentical progesterone over non-bioidentical progestin in the treatment of menopausal symptoms.
Further research supports the use of bioidentical progesterone in preference to non-bioidentical progestin. One study of menopausal women receiving HRT found that those receiving non-bioidentical progestin experienced greater vaginal bleeding and breast tenderness than those receiving bioidentical progesterone.153 Two other studies with menopausal women also determined that HRT with non-bioidentical progestin was associated with greater vaginal bleeding compared to those receiving bioidentical progesterone.154,155 Bioidentical progesterone also offers improvements in quality of sleep and cognitive function compared with non-bioidentical forms of the hormone.156,157
Estriol and Menopausal Symptoms
Studies have shown estriol to be effective in the treatment of menopausal symptoms. In one investigation, 52 postmenopausal women were given 2 mg, 4 mg, 6 mg, or 8 mg/day of oral estriol for six months. In all patients, vasomotor symptoms of menopause (such as hot flashes) were decreased. The most improvement was experienced by women taking the highest dose of 8 mg. There were no signs of endometrial hyperplasia confirmed by endometrial biopsy over the six-month treatment period. Mammograms were obtained on six of the patients who had breast hyperplasia at the study’s outset, and no further changes were seen.158
In another trial, researchers studied the safety of estriol in the treatment of menopausal symptoms. Fifty-three women with either surgically induced or natural menopause were given 2 mg of oral estriol/day for 12 months. Endometrial biopsy and breast ultrasound found normal results in all women. The authors concluded that over a 12-month period, “estriol appeared to be safe and effective in relieving symptoms of menopausal women.”149
A 5-year study demonstrated the successful use of estriol in the treatment of menopausal symptoms. In 71% of the participants, hot flashes and sweating were eliminated completely, while in 21% they were weaker and occurred less frequently. Depressive moods were abolished in 24% of the women and were reduced in severity in another 33%. Reductions in forgetfulness, loss of concentration, irritability, and heart palpitations were also recorded, while the number of women who experienced migraine headaches dropped by two-thirds. Thrombophlebitis occurred in two patients and there were two cases of mammary cancers, which the investigators did not believe were related to the estriol treatment.159
Given the wealth of data demonstrating the superiority of bioidentical HRT over non-bioidentical HRT, a noted researcher in hormone replacement therapy proclaimed that “Physiological data and clinical outcomes demonstrate that bioidentical hormones are associated with lower risks, including the risk of breast cancer and cardiovascular disease, and are more efficacious than their… animal-derived [non-bioidentical] counterparts. Until evidence is found to the contrary, bioidentical hormones remain the preferred method of HRT.”82
Beyond Menopause: Enhancing Health with Bioidentical Hormones
The benefits of bioidentical hormones are by no means limited to the relief of menopausal symptoms. Maturing women can reap long-term health benefits by restoring youthful hormonal balance with the use of bioidentical hormones. The Life Extension Foundation® has written extensively regarding the importance of maintaining optimal hormone balance as we age in order to ensure optimal health.
Estriol Increases Bone Mineral Density
One of the unfortunate consequences of decreased estrogen production in maturing women is the loss of bone density, with the potential to develop osteoporosis. A Japanese study involving 75 postmenopausal women found that after 50 weeks of treatment with 2 mg/day of oral estriol cyclically and 800 mg/day of calcium lactate, women had an increase in bone mineral density with no increased risk of endometrial hyperplasia (uterine tissue overgrowth that may precede cancer).160 In a second study emanating from Japan, researchers treated postmenopausal and elderly women with 2 mg/day of oral estriol and 1,000 mg/day of calcium lactate versus 1,000 mg/day calcium lactate alone. Bone mineral density significantly increased in women who received estriol, while the women who did not take estriol experienced a decrease in bone mineral density.150
Similar research has confirmed these findings. In this investigation, 25 postmenopausal women were given either 2 mg/day of estriol plus 2 gram/day of calcium lactate, or 2 grams/day of calcium lactate alone for one year. Bone mineral density was significantly reduced in the group that received calcium alone (without estriol). In contrast, the group that received estriol plus calcium experienced a 1.66% increase in bone mineral density after one year. Furthermore, biochemical markers of bone resorption were significantly decreased in the estriol group. “These data indicate that the acceleration of bone turnover usually observed after menopause was prevented by treatment with E3 [estriol],” the authors of this study noted.161
The most dramatic improvements in bone density were reported by scientists in the Journal of Bone and Mineral Metabolism. In this study, 41 women over age 49 with decreased bone density received either 2 mg/day estriol orally with calcium, or calcium alone for 10 months. The group receiving estriol experienced a striking 5% increase in bone density, while the group that did not receive estriol experienced a 3% decrease in bone density.162
Estriol Enhances Sexual and Urinary Health
Postmenopausal women often suffer from urinary incontinence or recurrent urinary tract infections caused in part by hormone deficiencies.
In a prospective, randomized, placebo-controlled study, 88 women were given 2 mg intravaginal estriol suppositories (once daily for two weeks, then twice weekly for six months) or placebo. Of the women in the estriol group, 68% reported improvement in symptoms of incontinence, while only 16% improved in the placebo group.163
In another randomized, double-blind, placebo-controlled trial, women with recurrent urinary tract infections were given either intravaginal estriol cream (containing 0.5 mg estriol, once daily for two weeks, then twice weekly for eight months) or placebo. Incredibly, the incidence of urinary tract infection was reduced by 91% in the estriol group compared with placebo.164
The substantial decrease in estrogen that occurs after menopause can lead to a condition called atrophic vaginitis. The symptoms, which include vaginal dryness, vaginal burning, and painful sex can be quite bothersome for aging women. Fortunately, the use of estriol can offer relief for women suffering from these symptoms. One group of researchers, who prescribed oral estriol to 62 postmenopausal women with vaginal symptoms in a double-blind and placebo-controlled fashion, concluded that “estriol has a remarkably beneficial effect on the vaginal epithelium.”165 Another group of researchers prescribed an estriol cream for women with atrophic vaginitis. After 4 weeks of treatment, the researchers noted that “atrophy of vaginal epithelium and chronic vaginitis stopped or significantly decreased… The subjective complaints relating to the estrogen deficiency (vaginal burning and dryness, itching, dyspareunia [painful sex] and urinary dysfunctions) ceased. Side-effects and complications during the treatment were not found.”166
In a study conducted in Japan, oral estriol (2 mg/day) was administered to 59 postmenopausal women complaining of vaginal itching or discharge. After 14 days of treatment, substantial improvements were noted in the women’s vaginal flora. The authors of the study concluded: “Estriol… has the potential to be highly useful for the treatment of atrophic vaginitis.”167
Estriol Promotes Youthful Skin
One reason that facial skin “shrivels” as we age is that our natural hormone production markedly declines. To make matters worse, blood microcirculation to our skin is reduced as we grow older, thereby depriving our skin of the small amount of natural hormones our body still makes.168 A large number of published scientific studies reveal that estrogen exerts potent anti-aging effects on the skin.169-178 The topical application of natural estrogen can produce dramatic improvements to the skin without systemic absorption concerns.
The deficiency of estrogen that characterizes menopause exacerbates the effects of both normal and environmentally-induced skin aging. According to the findings of a scientific study published in 2007, “Estrogens prevent skin aging. They increase skin thickness and improve skin moisture.”178 Another recent study came to the same conclusion, i.e. “skin aging can be significantly delayed by the administration of estrogen.”170
A critical mechanism by which estrogen maintains a youthful plump appearance is by increasing the synthesis of collagen, which is the skin’s underlying support structure. Collagen atrophy is a major factor in skin aging. There is a strong correlation between skin collagen loss and estrogen deficiency at menopause.169
Skin aging, especially in the face, is associated with a progressive increase in sagging tissues and a reduction in elasticity. In menopausal and postmenopausal women, estrogen administration increases collagen content, dermal thickness and elasticity, while decreasing aging dry skin.169,172
Estrogens exert significant effects on skin physiology by modulating the effects of key epidermal and dermal cells.170 In fact, the skin is an important estrogen-responsive tissue, and without the growth promoting effects of estrogen, it literally withers away.171 The very thin skin observed in the elderly can be directly correlated to a lack of estrogens needed to generate collagen and maintain skin thickness.171
Topical estrogen application has been shown to be safe and effective in preventing skin aging. In a study published in February 2007, a group of women who were already taking oral estrogen drugs were given a topical 0.01% estrogen cream. After only four months, both dermal and epidermal thickness was enhanced, as were dermal collagen levels. This study showed that topical estrogen application provided rapid and definitive anti-aging effects even in women who had high systemic estrogen blood levels.172 The significance of this study is that it shows how quickly a small amount of estrogen delivered directly into the skin induces profound anti-aging effects.
A six-month study of perimenopausal women was conducted at the University of Vienna in Austria comparing the topical application of estriol and estradiol creams. The doctors found that skin symptoms of aging improved, and that those treated with estriol obtained superior results in decreased wrinkle depth, with no systemic hormonal side effects noted.173
In another study, twenty women with mild crow’s feet, rough-textured skin, and moderate skin tone with some blotching and imperfections applied a topical solution containing estriol with 15 other ingredients on only one side of their faces over a six-week period. All of the subjects reported that their skin texture on the treated side was smoother and that the quality of their skin had improved, while 90% and 80% said that the moisture content and elasticity of their skin had increased, respectively, giving them a healthier and younger-looking appearance. Clinical assessments showed a baseline improvement of 19% increase in elasticity and 9% increase in moisture in the skin after just one week.179