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First-line Hormone Therapy Options: Transdermal Estrogen and Micronized Progesterone “ Growing body of evidence that each type of estrogen and progestogen, route of administration and timing of therapy has distinct beneficial and adverse effects.” The North American Menopause Society. Menopause, 2010;17(2):242-55.
Overall Benefits of Hormone Therapy (HT)
SOGC MeNOpAuSe ANd OSTeOpOrOSiS updATe 2009: recommendations for Hormone Therapy
J Obstet Gynaecology Can, 2009; Jan;31(1)(Suppl 1).
• HT should be prescribed at the appropriate dose, route and duration according to symptoms and to achieve treatment goals
• Primary indication for HT: Management of moderate to severe menopausal symptoms (Grade A)
• Vaginal therapy for vaginal symptoms only
• Prolonged therapy may be offered with appropriate assessment and counselling
• HT should not be prescribed for primary or secondary prevention of cardiovascular disease or primary prevention of dementia (Grade A)
Micronized progesterone
progestogen indications
(NAMS. Menopause, 2010.)
• Metabolites act at non-sex-steroid receptor sites • Primary menopause-related indication is endometrial protection from unopposed ET • Not necessary with standard doses of vaginal ET (including vaginal ring) - Sedation with higher doses of oral progesterone (utilized therapeutically for sleep)
• Adequate progestogen (as CC-EPT or CS-EPT) recommended with intact uterus - 11-deoxycorticosterone has aldosterone properties (may reduce fluid retention) • Progestogen not generally indicated with ET post-hysterectomy - May cause nausea and dizziness - Contraindicated in patients with peanut allergy Micronized progesterone
Medroxyprogesterone Acetate
CEE with cyclic MP has the most favourable effect on HdL-C
and no excess risk of endometrial hyperplasia
The Writing Group for the pepi Trial. JAMA, 1995;
273:202.
In a woman with a uterus, CEE with cyclic MP has the most favourable effect on HdL-C and no excess risk of endometrial
hyperplasia
Breast Cancer
Estrogen in combination with micronized progesterone is Estrogen therapy used with progestin has been associated not associated with an increased risk of breast cancer
with an increased risk of breast cancer within three to
French e3n Cohort Study, Fournier, Br Ca res. Treat,
2008;107:103-111.
Estrogen/Progesterone RR 1.00 (0.83-1.22) Estrogen/dydrogesterone RR 1.16 (0.94-1.43) Micronized progesterone does not counteract estrogen-mediated Medroxyprogesterone Acetate may negate the beneficial effects on blood vessels rosano GM, et al. J AM Coll Cardiol, 2000;36:2154-2159.
Bleeding patterns
Micronized progesterone is associated with a lower incidence of bleeding overall Lorrain J, et al. Int J Gynecol Obstet, 1991;13:297-311.
Marengo M, et al. Proceedings of the 4th International
Symposium in Osteoporosis, 1993:331-333.
Developed by the Society of Obstetricians and Gynaecologists of Canada (SOGC) Supported by an unrestricted educational grant from Merck in Canada. Transdermal estrogen
Clinical pearls
The key differences between oral and transdermal therapy is in their metabolism: • Total surface area gel spread determines level of circulating estrogen, • Orally-administered HT must go through first-pass metabolism in the liver and
digestive tract before entering the circulation. • Surface area of patch determines rate of absorption and circulating levels of estrogen • Transdermal preparations do not go through this route, entering directly into • The gel must be applied to same surface area with regular frequency as prescribed Prescribe as a first-line therapy to relieve menopausal symptoms for any woman, • The patch can be applied to any area with regular frequency as prescribed in addition to patients with underlying medical conditions which may make transdermal HT the preferred route of administration: • Surface area of the same dose of gel can be decreased, or decrease the number of pumps • All matrix patches can be cut down as necessary to decrease surface area for absorption • Results in decreasing levels of circulating estrogen • Reservoir patches cannot be cut (i.e., Estraderm) Transdermal estrogen
Oral estrogen
risk of stroke
Increased risk of stroke with oral HT, including low-dose estrogen, estrogen alone or combined estrogen plus Scarabin p-Y et.al. Lancet, 2003; 362 :428-432.
Santen rJ et al., postmenopausal hormone therapy: an endocrine
Society Scientific Statement. J Clin Endocinol Metab, 2010; 95
Suppl 1:S7-S66.
These types of hormone therapy may increase stroke Canonico M, et al. Circulation, 2007; 115:840.
risk–this translates into an absolute excess risk of about 4.5 additional cases per 1000 women per 5 years of use Cardiovascular risk
Decreased CV risk in patients with metabolic Oral estrogen can further elevate tryglyceride levels Sanada N, et al. Menopause, 2004;11:331.
Walsh BW, et al. N Engl J Med, 1991;325:1196.
Modena MG. et al. Am J Med, 2002; 113:331-4.
Lewandowski KC. J Clin Endo, 2006; 91: 3123-30.
Che MC. Am J Ob Gyn, 2008; 199: 526.e1-526.e7.
The Writing Group for the pepi trial. JAMA, 1995; 273:199-208.
Metabolism
Transdermal preparations bypass liver, entering HT must go through first-pass metabolism in the liver
and digestive tract before entering the circulation Steady State
Compliance
Stomach upset due to oral estrogen intake Contraindications to HT
Non-contraindications to HT
• Unexplained/undiagnosed vaginal bleeding prior to investigation • Active thromboembolic disease (estrogen only) Developed by the Society of Obstetricians and Gynaecologists of Canada (SOGC) Supported by an unrestricted educational grant from Merck in Canada.

Source: http://www.osteoporosisandu.ca/resources/MenoMDtool.pdf