So, here is the dos and don'ts of menopause hormonal health management and the relevant research papers, in case your doctor is one of those confused and misinformed.
Important: Don't let your doctor overdose you.
- Doctors are brain washed to think: most of oral natural progesterone or estrogen gets "digested", therefore it requires 10 times more than what you actually need.
- Doctors are brain washed to think: natural progesterone or estrogen does not get absorbed much through skin, therefore it requires 10 times more than what you actually need.
- Doctors are brain washed to think: your blood hormone level (98% inactive, 2 % active form of hormone) has to achieve the same level as normal reproductive age level by supplementing active form of hormone (micronized powder in gel cap or liquid in cream, oil, gel, patch, spray, etc.), and measuring inactive form of hormones. Although what really matters is the level of active form of hormones and the traditional blood test is not sensitive enough to keep track the active form of hormones.
- One time I consulted a doctor who seemed better
informed. When I asked him about oral progesterone, he prescribed me
100mg capsules. It made me so tired and lethargic I had to quit after 2
days.
Dos:
1. Use natural bio-identical hormones at lowest dose necessary in transdermal forms (skin cream*, patch, oil, spray, vaginal gel/cream/ring**). The higher the dosage the more bleeding and spotting will occur, not to mentions all the overdose side effects and hormonal imbalance risks. For many women with intact ovaries, 20mg/day progesterone cream without estrogen can completely eliminate hot flashes and other menopausal symptoms during the early post menopause years (see the table below). 0.025mg/day transdermal estradiol + progesterone is enough to control menopause symptoms for most women, 0.05mg/day transdermal estradiol + progesterone will take care the rest[1]. For protection of uterine lining (endometrium), as low as 10mg/day vaginal progesterone can protect uterus against estrogen stimulated proliferation, although individual differences exist. Keep in mind that maximum daily progesterone secretion during normal cycle is around 30mg.
*Caution: for the progesterone cream to be well absorbed and protected from oxidation, it has to be suspended in some protective delivery medium (e.g. liposome) or dissolved in protective oil such as vitamin E. Gritty and/or watery cream is not effective. High quality cream will resist oxidation up to 3 months after opening, but not much more. Also, the cream has to be rubbed in well to clean and soft part of skin free of mineral oil to ensure absorption.
**Caution: vaginal rings are know to cause tissue irritations and should be monitored closely.
2. Start progesterone supplementation with the first sign of menopause transition to prevent estrogen dominance. The progesterone level drops several years before menopause, while estrogen level stays normal or higher[2]. Even during the early post menopause years, the estrogen level stays high enough to stimulate endometrial proliferation[3], therefore progesterone supplementation is needed to prevent estrogen dominance syndromes including uterine cancer.
3. Use continuous regimen (no estrogen only days). There is no need to induce bleeding to protect your uterus in post menopause years (D L Moyer et al. 1993[4]). Low dose progesterone (as low as 10 mg/day vaginal and 30 mg/day skin cream) is enough to protect uterus lining (endometrium) in the continuous regimen when combined with low to medium dose estradiol (see the table below). However, it is normal to see some spotting or bleeding at the beginning of continuous regimen. Continuous regimen is also important for protection against ovarian cancer[5].
4. Get regular check-up. Although maintaining healthy hormonal balance the right way will reduce various health risks, it will not make you bullet proof.
Don'ts:
1. Use of unopposed estrogen is not justified even for women without uterus. Besides the well known uterine cancer risk, it raises risks of breast cancer[6], ovarian cancer [7] [8], stroke[9], dementia[10] and a wide range of estrogen dominance syndromes. In other words, whenever you use estrogen, you need to use progesterone (bio-identical) along with it. Anybody who says otherwise is ignorant of the differences between the real and fake progesterone as well as the serious nature of estrogen dominance syndromes.
2. Use of fake hormones of any kind is not justified for any condition. They raise breast cancer risk[11], blood clot risk[12], bad cholesterols[13], to mention just a few. How can you tell which one is real? If the active ingredients does not simply say "progesterone" or "estradiol" or "17-beta estradiol", stay away. Note also that all birth control drugs are fake hormones.
3. Use of oral hormone delivery (pills, capsules) is not justified for any condition. It negatively affects cholesterol[14], cardio-vascular risk[15], and metabolic risk factors[16]. It is less effective in controlling uterine lining[17]. It burdens liver and kidney[18], raises gallbladder disease risk[19]. Oral progesterone can cause fatigue, depressive mood, and PMS like symptoms due to the high standard dose (100 mg capsule is the lowest available) and high rate of metabolic conversions, especially when it is not in balance with estrogen level[20]. Progesterone and its metabolites are GABAa receptor activators (i.e. They act as tranquilizer). Given a large enough dose, it can induce drunkenness and slow down digestive as well as cognitive functions[21].
4. Use of venous blood hormone tests for measuring hormone supplementation level is useless. It's been known that the plasma hormone levels and uterine lining status do not correlate (Trevoux, et al. 1986[22], Sojo-Aranda et al. 1988[23], ). The same applies when you try to see the effects of hormone supplementation (Ficicioglu et al. 2004[24], Tavaniotou et al. 2000[25], Friedler et al. 1999[26]). Measuring hormone levels in venous blood, be it plasma or red blood cells, free or bound, is like measuring oxygen in venous red blood cells and concluding the person is suffocating. Saliva or capillary blood spot test reflects what's delivered to the tissues much better. However, there is no need to use such indirect measures that go through a rapid change with each application[27] [28] [29]. When you need to know if the symptoms improved, you measure the symptoms. When you need to know if the uterus is protected, you check the uterus, and so forth.
Table 1. Continuous regimen studies with transdermal (non oral) natural progesterone on post menopausal women
Study
|
Size/duration
|
Estrogen
|
Progesterone
|
Results
|
Leonetti et al. 1999[30]
|
43 (47 placebo) women within 5 years of natural menopause,
1 year trial
|
no estrogens
(daily multivitamins and 1200 mg of calcium)
|
quarter teaspoon of cream (containing 20 mg progesterone) to the skin daily or placebo
|
vasomotor symptom relief: 25 of 30 (83%), 5 of 26 (19%) with placebo, complete relief in 11 of 30. Most reached maximum relief after the first month.
no bone loss or gain
spotting: 8 women
|
Leonetti et al. 2003[31]
|
32 women
time since menopause (7.1 ±6.2 years)
28 day trial
|
premarin (oral conjugated estrone) 0.625mg/day
started 2 weeks before progesterone to stimulate endometrium
|
twice daily transdermal application of 0%, 1.5%(30mg /day), or 4.0%(80mg/day) P in 1000 mg cream, adjusted by body weight
|
The endometrial proliferation scores (EPS)
Initial EPS=2 a Final EPS=0 for 30mg and 80mg group, no change for 0% (placebo) group
0=inactive,
1=scantly proliferative, 2= moderately proliferative, 3= proliferative, 4= highly proliferative.
Spotting occurred in 3 during the washout estrogen-only period, 3 during the first 2 weeks of P treatment (2 in 0% group, 1 in 1.5% group)
greater than 98% compliance
|
Arvind Vashisht et al. 2005[32]
|
41 (3 of 44 did not complete)
48 week trial |
1 mg transdermal estradiol daily
|
40 mg transdermal natural progesterone cream daily
|
At 24 weeks, 48% remained entirely amenorrhoeic. At 48 weeks 35% had been entirely amenorrhoeic and 50% had either no bleeding or spotting alone. The number of bleeding episodes did not reduce with time.
32 % proliferative or hyperplastic.
|
Arvind Vashisht at al. 2005[33]
|
same as above
|
same as above
|
same as above
|
Women reported significant reductions in menopausal symptoms, as measured by the Green Climacteric Scale, after 24 and 48 weeks of combined treatment.
|
D de Ziegler et al. 2000[34]
|
67 women for 6 months
|
estrogens (not specified)
most likely transdermal estradiol 0.05 mg |
vaginal progesterone gel (Crinone 4%= (45 mg) twice weekly
|
54 (80.6%) of 67 amenorrhoeic throughout 6 months. No hyperplasia
|
Cicinelli, Ettore et al. 2002[35]
|
26 women,
I year |
transdermal estradiol 0.05 mg
|
vaginal progesterone gel (Crinone 4%= 45 mg) twice weekly
|
287/350 (82%) cycles were amenorrheic. endometrial atrophy in 24 (92.3%) cases and signs of decidualization in 2 cases.
|
Hamada et at. 2003[36]
|
20 women
16 weeks
|
vaginal ring estradiol 160 microg/day
|
4 month vaginal ring progesterone 10 or 20 mg/day.
|
Significant decreases in the incidence of hot flushes and night sweats as well as a striking improvement in mood scores as early as 2 weeks after insertion.
Increased vaginal discharge within the first 6 weeks.
Endometrium thickness of <3mm
Vaginal bleeding was more frequently apparent among users of the 20mg ring, although bleeding and spotting were confined to the first 6 weeks.
|
Ben-Chetrit et al. 2005[37]
|
29 women
ring kept 4 to 6 months
11 dropped out due to side effects
|
same as above
|
same as above
|
Reduced climacteric symptoms, prevented endometrial proliferation, and provided an acceptable bleeding pattern.
Endometrial thickness increased in 6(20%). |
Suvanto-Luukkonen et al. 1998[38]
|
15 women
I year trial |
percutaneous estradiol gel containing 1.5 mg estradiol daily
|
natural progesterone 100 mg daily vaginal
|
After 12 months of therapy, no significant change in endometrial thickness (2.5 mm -> 2.4mm), 5 had inactive or atrophic endometrium, 10 were proliferative. No hyperplasia.
|
Notes: Red indicates excessive dosage, oral form, or otherwise problematic, that should not be followed.
[1] H Gadomska, E Barcz, A Cyganek, Y Leocmach, H Chadha-Boreham, L Marianowski. Efficacy and tolerability of low-dose transdermal estrogen (Oesclim) in the treatment of menopausal symptoms. Curr Med Res Opin. 2002 ;18 (2):97-102,
[2] Santoro N, Brown JR, Adel T, Skurnick JH. Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab. 1996;81(4):1495-1501.
[3] R Trevoux, J De Brux, M Castanier, K Nahoul, J P Soule, R Scholler. Endometrium and plasma hormone profile in the peri-menopause and post-menopause. Maturitas. 1986 Dec ;8 (4):309-26
[4] D L Moyer, B de Lignieres, P Driguez, J P Pez. Prevention of endometrial hyperplasia by progesterone during long-term estradiol replacement: influence of bleeding pattern and secretory changes. Fertil Steril. 1993 May ;59 (5):992-7
[5] Tomas Riman, Paul W Dickman, Staffan Nilsson, Nestor Correia, Hans Nordlinder, Cecilia M Magnusson, Elisabete Weiderpass, Ingemar R Persson Hormone replacement therapy and the risk of invasive epithelial ovarian cancer in Swedish women. J Natl Cancer Inst. 2002 Apr 3;94 (7):497-504 1.
[6] Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Agnes Fournier, Franco Berrino, Francoise Clavel-Chapelon. Breast Cancer Res Treat. 2007 Feb 27.
[7] James V. Lacey Jr. et al., Menopausal Hormone Replacement Therapy and Risk of Ovarian Cancer, 288 JAMA 334 (2002).
[8] Karen Wernli, Polly Newcomb, John Hampton, Amy Trentham-Dietz, Kathleen Egan. Hormone therapy and ovarian cancer: incidence and survival. Cancer Causes Control. 2008 Feb 9
[9] Garnet L Anderson et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004 Apr 14;291 (14):1701-12
[10] Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, Fillit H, Stefanick ML, Hendrix SL, Lewis CE, Masaki K, Coker LH; Women's Health Initiative Memory Study. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA. 2004 Jun 23;291(24):2947-58.
[11] Agnes Fournier, Franco Berrino, Francoise Clavel-Chapelon. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat. 2007 Feb 27
[12] J L Ambrus, I B Mink, N G Courey, K Niswander, R H Moore, C M Ambrus, M A Lillie. Progestational agents and blood coagulation. VII. Thromboembolic and other complications of oral contraceptive therapy in relationship to pretreatment levels of blood coagulation factors: summary report of a ten-year study. Am J Obstet Gynecol. 1976 Aug 15;125 (8):1057-62,
[13] U B Ottosson Oral progesterone and estrogen/progestogen therapy. Effects of natural and synthetic hormones on subfractions of HDL cholesterol and liver proteins. Acta Obstet Gynecol Scand Suppl. 1984 ;127 :1-37,
[14] M Erenus, B Karakoc, A Gurler Comparison of effects of continuous combined transdermal with oral estrogen and oral progestogen replacement therapies on serum lipoproteins and compliance. Climacteric. 2001 Sep ;4 (3):228-34
[15] Karine Lacut, Emmanuel Oger, Jean-Herve Abalain, Marie-Pierre Moineau, Dominique Mottier. Effects of oral and transdermal 17 beta-estradiol combined with progesterone on homocysteine metabolism in postmenopausal women: a randomised placebo-controlled trial. Atherosclerosis. 2004 May ;174 (1):173-80
[16] J C Stevenson, D Crook, I F Godsland, B Lees, M I Whitehead. Oral versus transdermal hormone replacement therapy. Int J Fertil Menopausal Stud. 1993 ;38 Suppl 1
[17] Tavaniotou et al. Comparison between different routes of progesterone administration as luteal phase support in infertility treatments. Hum Reprod Update. 2000, 6 (2):139-48
[18] K A Steingold, D W Matt, D DeZiegler, J E Sealey, M Fratkin, S Reznikov. Comparison of transdermal to oral estradiol administration on hormonal and hepatic parameters in women with premature ovarian failure. J Clin Endocrinol Metab. 1991 Aug ;73:275-80
[19] Bette Liu, Valerie Beral, Angela Balkwill, Jane Green, Sian Sweetland, Gillian Reeves. Gallbladder disease and use of transdermal versus oral hormone replacement therapy in postmenopausal women: prospective cohort study. BMJ. 2008 ;337 :a386
[20] B de Lignieres, M Vincens. Differential effects of exogenous oestradiol and progesterone on mood in post-menopausal women: individual dose/effect relationship. Maturitas. 1982 Apr ;4 (1):67-72.
[21] E W Freeman, L Weinstock, K Rickels, S J Sondheimer, C Coutifaris. A placebo-controlled study of effects of oral progesterone on performance and mood. Br J Clin Pharmacol. 1992 Mar ;33:293-8
[22] R Trevoux, J De Brux, M Castanier, K Nahoul, J P Soule, R Scholler Endometrium and plasma hormone profile in the peri-menopause and post-menopause. Maturitas. 1986 Dec ;8 (4):309-26
[23] I Sojo-Aranda, R Alonso-Uriarte, M Gonzalez-Diddi, V Cortes-Gallegos. The biological expression of natural progesterone. J Steroid Biochem. 1988 Aug ;31 (2):219-22
[24] C Ficicioglu, B Gurbuz, S Tasdemir, S Yalti, H Canova. High local endometrial effect of vaginal progesterone gel. Gynecol Endocrinol. 2004 May ;18 (5):240-3
[25] Tavaniotou et al. Comparison between different routes of progesterone administration as luteal phase support in infertility treatments. Hum Reprod Update. 2000, 6 (2):139-48
[27] O'leary P.; Feddema P.; Chan K.; Taranto M.; Smith M.; Evans S. Salivary, but not serum or urinary levels of progesterone are elevated after topical application of progesterone cream to pre-and postmenopausal women. Clinical Endocrinology, Volume 53, Number 5, November 2000 , pp. 615-620(6)
Topical application of progesterone cream will show up in saliva within 30 to 60 min., and reaches high peak in 1 to 4 hours, then falls thereafter.
[28] E Cicinelli, S Sabatelli, D Petruzzi, S Stragapede, M Lapenna, G Balzano [Transvaginal absorption of an oleic solution of progesterone (Gestone) in fertile women] Minerva Ginecol. 1995 Mar ;47 (3):99-102
P in oil 100 mg, Blood P level peaked in 1 to 4 hours, was still higher than baseline after 24 hours.
[29] B Villanueva, R F Casper, S S Yen. Intravaginal administration of progesterone: enhanced absorption after estrogen treatment. Fertil Steril. 1981 Apr ;35 (4):433-7
The peak level can be 20 to 40 times baseline. After how much P given not mentioned in the abstract.
[30] H B Leonetti, S Longo, J N Anasti.Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss. Obstet Gynecol. 1999 Aug ;94 (2):225-8
This confirmed the common observation of those doctors who have been recommending progesterone skin cream for menopausal symptoms that 2 in 3 women in the US can manage menopause with progesterone only therapy.
[31] Leonetti H, Wilson KJ, Anasti JN. Topical progesterone cream has an antiproliferative effect on estrogen-stimulated endometrium. Fertil Steril 2003; 79: 221-222.
Premarin 0.625mg was the most often prescribed estrogen in the US at the time, and they demonstrated natural progesterone cream can be combined effectively with it instead of Provera, which has been know for its multitude of side effects.
[32] Arvind Vashisht, Fred Wadsworth, Adam Carey, Beverley Carey, John Studd. Bleeding profiles and effects on the endometrium for women using a novel combination of transdermal oestradiol and natural progesterone cream as part of a continuous combined hormone replacement regime. BJOG. 2005 Oct ;112 (10):1402-6
I wonder why they used 1 mg /day transdermal estradiol, which is 40 times higher than what's needed. No wonder 40mg/day progesterone cream could not control endometrium adequately. Doctors at Chelsea and Westminster Hospital, London, UK are starting to realized that they cannot simply dismiss progesterone cream based on serum/plasma hormone level like they did in their 2000 study. However, they did not learn much about the right estradiol dosage since. Or was it their main aim to discourage the use of progesterone cream? Whatever the reason, I hope they are not routinely prescribing such a high amount of estradiol to their menopause patients.
[33] Arvind Vashisht, Fred Wadsworth, Adam Carey, Beverley Carey, John Studd. A study to look at hormonal absorption of progesterone cream used in conjunction with transdermal estrogen. Gynecol Endocrinol. 2005 Aug ;21 (2):101-5
[34] D de Ziegler, R Ferriani, L A Moraes, C Bulletti. Vaginal progesterone in menopause: Crinone 4% in cyclical and constant combined regimens. Hum Reprod. 2000 Jun ;15 Suppl 1 :149-58
[35] Cicinelli et al. Twice-weekly transdermal estradiol and vaginal progesterone as continuous combined hormone replacement therapy in postmenopausal women: A 1-year prospective study. American Journal of Obstetrics & Gynecology. 187(3):556-560, September 2002.
[36] A L Hamada, T Maruo, T Samoto, S Yoshida, H Nash, I M Spitz, E Johansson. Estradiol/progesterone-releasing vaginal rings for hormone replacement therapy in postmenopausal women. Gynecol Endocrinol. 2003 Jun ;17 (3):247-54
With the local effect of transdermal delivery, 10 mg/day progesterone is enough to control endometrium even with relatively high dose of estradiol used in this study. They also demonstrated that enough hormones reached brain to control menopausal symptoms and mood.
[37] Avraham Ben-Chetrit, Drorit Hochner-Celnikier, Tzina Lindenberg, David Zacut, Shlomo Shimonovitz, Hadassa Gelber, Irving M Spitz. Vaginal ring delivering estradiol and progesterone: a possible alternative to relieve climacteric symptoms. Isr Med Assoc J. 2005 May ;7 (5):302-6.
The vaginal ring was apparently abrasive and irritated the tissues, which caused 11 of 28 people to dropout. I wonder how they did in the Japanese arm of the study, which does not mention anything about it in the abstract. I wonder who would use vaginal rings if they know they can try progesterone skin cream to see if it work for them.
[38] E Suvanto-Luukkonen, H Malinen, H Sundstrom, J Penttinen, A Kauppila. Endometrial morphology during hormone replacement therapy with estradiol gel combined to levonorgestrel-releasing intrauterine device or natural progesterone. Acta Obstet Gynecol Scand. 1998 Aug ;77 (7):758-63
This study was done to demonstrate the superiority of levonorgestrel-releasing intrauterine device (LNG-IUD). The high doses reflect the attempt to achieve "normal" plasma level commonly believed necessary at the time. Too bad they did not create natural progesterone releasing device. Although, I cannot imagine inserting IUD in my uterus even if it is natural progesterone, much less a fake progesterone like levonorgestrel.
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Before you post your HRT questions, please try what I think safe and effective for at least 3 months: estradiol 0.025~0.050mg/day patch, with 20~40mg/day progesterone cream (about 1000mg progesterone in 2oz cream). You can also add DHEA 5~10mg /day.
That is the only recommendation you will get from me.