Articles by Bent Formby, Phd.
Summary of 11 Significant
Published BHRT Studies
Bent Formby, PhD.”Together with more than 200 other clinical studies it can be tentatively concluded that unopposed 17beta-estradiol in transdermal dosages of 0,05 mg to 0,1 mg delivered daily effectively reversed bone loss, vasomotor symptoms, memory loss etc in menopausal women during either short-term few months up to long-term several years studies. Progesterone in few studies is given in very low dosages to protect the endometrium.”
Examples of published controlled clinical trials documenting the efficacy of various transdermal low doses of 17beta-estradiol in treatment of menopausal symptoms. In some studies low concentrations of progesterone was given for protection of the endometrium. Note the daily administered dosages of estradiol to obtain clinical significant responses ranged from 0.02 mg to 1.5 mg. Progesterone was usually given in daily doses of 10 mg to 50 mg during the last two weeks of a 4 weeks treatment period.
1. Moyer DL et al. Prevention of endometrial hyperplasia by progesterone during long-term estradiol replacement: influence of bleeding pattern and secretory changes. Fertil Steril 1993; 59:992-7
These women were treated with daily percutaneous 1.5 mg 17beta-estradiol and 12 days monthly with 200 mg oral micronized progersterone. During the 5-year study endometrial hyperplasia was prevented.
2. Nielsen T et al. Pulsed estrogen therapy improves postmenopausal quality of life: A 2 year placebo-controlled study. Maturitas 2005; (in press)
Early postmenopausal women were treated daily with 0.15 or 0.3 mg 17beta-estradiol. Women with intact uterus received, in addition, oral micronized progesterone 200 mg/day, 14 days out of 28. Pulsed estradiol therapy had a pronounced effect not only on vasomotor symptoms, but also improvement in the quality of life.
3. Burry KA et al. Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen. Am J Obstet Gynecol 1999; 180:1504-11
All women were treated with 17beta-estradiol administered transdermally at a dose of 0.05 mg/d. Progesterone was administered at a dose of 30 mg/d with a cream. The percutaneous administration of estrogen and progesterone appears to be a safe and effective route of administration.
4. Liu PY et al. A randomized placebo-controlled trial of short-term graded transdermal estradiol in healthy gonadotropin-releasing hormone agonist-suppressed pre- and postmenopausal women: effects on serum markers of bone turnover, insulin-like growth factor-I, and osteoclastogenic mediators. J Clin Endocrinol Metab 2005; 90:1953-60
Note in this study estradiol therapy was applied incrementally, with each weekly dose of 0.05, 0.1, 0.15, and 0.20 mg/d administered to mimic the estradiol changes typifying the follicular phase of the 28-day menstrual cycle. No progesterone was added. The study found that lower dose of estradiol rapidly increases osteoblastic collagen synthesis. A positive effect of estradiol on bone formation was observed.
5. Nelson RM et al. Effects in post-menopausal women of transdermal estrogen associated with progesterone upon the removal from the plasma of a microemulsion that resembles low-density lipoprotein (LDL). Maturitas 2005; (in press)
Note transdermal 17beta-estradiol was administered at increasing-decreasing dose so that the hormonal variation of the menstrual cycle was mimicked. The estradiol dosages during 4 weeks treatment periods were 0.038, 0.075, 0,100, and 0.38 mg. During the 3 and 4 week, 10 and 5 mg oral progesterone was added to the protocol. The study found that levels of “bad cholesterol” LDL significantly was reduced.
6. Abbas A et al. Contrasting effects of oral versus transdermal estrogen on serum amyloid A (SAA) and high-density lipoprotein-SAA in postmenopausal women. Artherioscler Thromb Vasc Biol 2004; 24:164-7
After 8 weeks of transdermal administration of 0,100 mg 17beta-estradiol it was found that the level of plasma SAA, an acute phase protein produced by the liver similar to C-reactive protein, was significantly reduced. No progesterone was used in the study.
7. Ettinger B et al. Effects of ultralow-dose transdermal estradiol on bone mineral density: A randomized clinical trial. Obstet Gynecol 2004; 104:443-51.
This is a 2-year study showing that unopposed transdermal administrated 17beta-estradiol at a daily dose of 0.046 mg significantly increased bone mineral density in elderly menopausal women without causing endometrial hyperplasia. No progesterone was added during the 2 year study period.
8. Kellokoski E et al. Estrogen replacement therapy increases plasma Ghrelin levels. J Clin Endocrinol Metab 2005; 2954-63.
Hysterectomized postmenopausal women received transdermal 17beta-estradiol therapy for 6 months at a daily dose of 1,0 mg. which increased serum levels of estrogen from baseline 31 pg/ml to 71 pg/ml. Note that an alcoholic gel was used as vehicle for estrogen which usually releases <50% of the hormone into the peripheral blood. Progesterone was not administered. It was found the estrogen increased ghrelin.
9. Speroff L at al. Efficacy and local tolerance of a low-dose, 7-day metrix estradiol transdermal system in the treatment of menopausal symptoms. Obstet Gynecol 1996; 88:587-92.
In this 12 weeks study a transdermal drug-dilevery system that dilevered 0.02 mg of 17beta-estradiol effectively reduced the frequency of moderate to severe vasomotor symptoms in 324 naturally menopausal women. Progesterone was not used.
10. Utian WH et al. Efficacy and safety of low, standard, and high dosages of an estradiol transdermal system (Esclim) compared with placebo on vasomotor symptoms in highly symptomatic menopausal patients. Am J Obstet Gynecol 1999; 181:71-9
0.025, 0.050 or 0,100 mg of 17beta-estradiol was daily delivered from an adhesive matrix. No progesterone was given in this study. It was shown that all three dosages of estradiol were effective in reducing vasomotor symptoms.
11. Weiss SR et al. A randomized controlled trial of four doses of transdermal estradiol for preventing postmenopausal bone loss. Transdermal Estradiol Investigator Group. Obstet Gynecol 1999; 94:330-6.
17beta-estradiol at doses of 0,025, 0,05, 0,06, and 0,1 mg/day was delivered by a transdermal system. After a study period of 2 years it was found that all four doses effectively prevented bone loss in postmenopausal women. No progesterone was given in this study.
Together with more than 200 other clinical studies it can be tentatively concluded that unopposed 17beta-estradiol in transdermal dosages of 0,05 mg to 0,1 mg delivered daily effectively reversed bone loss, vasomotor symptoms, memory loss etc in menopausal women during either short-term few months up to long-term several years studies. Progesterone in few studies is given in very low dosages to protect the endometrium.