• breast cancer
  
• stroke
  
• pulmonary embolism
  
• colorectal cancer
  
• endometrial cancer
  
• hip fracture
  
• death due to any cause
  

• 29% increase in coronary heart disease
  
• 41% increase in strokes
  
• 22% increase in cardiovascular disease
  
• 2100% increase in pulmonary embolism
  
• 26% increase in breast cancer
  

This is not the case with BHRT
Studies have shown that bioidentical hormones in balance do not increase the risk of these health problems but actually decrease the risk in some conditions.

Breast Cancer

Dimitrakakis  04 Menopause

508 Post menopausal  women referred for Testosterone supplementation for emotional lability, fatigue, loss of concentration, breast tenderness, loss of libido, sleep disturbances and weakness despite ERT FH of BCa 29% 508 women T pellet every 5 month in addition to CHRT (161 E/T, 347 E/T/P), f/u 5.8 years.The addition of testosterone to CHRT does not increase, and may reduce the incidence of BCa.

Natrajan / Gambrell  02  AJO&G

Conclusion: Estrogen replacement therapy does not increase the risk of recurrence or death in patients with early breast cancer (Stage 1 disease with <3 nodes pos.)


Birth Control

Greenblatt 76  AJOG

Step-down estradiol pellet dosing 2 pregnancies out of 1,668 cycles Cyclic progestogen Advantage over OCP
-Absence of GI sxs.
-Minimal side effects
-No HA, nausea
-No missed pills
“It is believed that by using natural estrogens, the incidence of thromboembolic disease may be greatly reduced.”


Bone Density
Oral and topical estradiol maintain bone density (86% of patients) Estradiol and estradiol with testosterone implants significantly increase bone density “Subcutaneous oestrogen is more effective than oral oestrogen in preventing osteoporosis….It also avoids problems of compliance that occur with oral treatment.”  Savvas 88 N=37,41; T 8.0, 8.5 years

Naessén 93  BJO&G

Bone preserving effects of SC E2 20 mg 35 women, mean age 67 years( 47-83) , TAH had been treated with E2 implants for 16 years (5.5-31 years)20-25% higher bone density than non users Physiologic levels of oestradiol No accumulation Low dose oestradiol implants maintain bone density long term.

Holland 94  O&G

Effect of E2 25 mg on bone loss 18 post men females compared to 18 women who did not wish treatment 25 mg E2 implanted every 6mos anterior abdominal wall Results Post treatment E2 320 pmol/l, range 114-813 (87.0 pg/ml)  FSH 28 IU/l (2-66)
At 1 year, there was a significant increase in bmd from baseline at lumbar spine (5.65%), femoral neck (3.38%) and hip (3.36%) but not Ward’s triangle “This dose is effective to prevent postmenopausal bone loss.”

Davis 95  Maturitas

Testosterone enhances estradiol’s effects on postmenopausal bone density and sexuality Prospective, randomized study
34 post-men females E2 50 or E2 50 & T 50 administered every 3 months for 2 years. E & T was superior to E2 alone in increasing bmd E & T group showed significantly greater improvement in sexual parameters. Total cholesterol and LDL fell in both groups as did total body fat Fat free mass increased in the E & T group.

Cravioto 01  Menopause

“Subcutaneous implantation of 25 mg of estradiol results in physiological, premenopausal estrogen concentrations in most women and is associated with considerable symptom relief without inducing significant adverse metabolic effects.”


Cardiovascular and metabolic effetcs

Seed 00  FP ij

CV risk factors on oral, TD and implant HRT Estrogen alone vs. estrogen plus norethisterone Estrogen alone vs. E2 plus T for the implant group All regimens reduced CV risk factors (oral: greatest reduction LDL and TG and increase HDL)  with the synthetic progestin attenuating some of the benefits of estrogen alone (fibrinogen and HDL) Implant group E2 50 and E2 50 & T100 Lowered LDL & TG, non significant lowered HDL Testosterone did not attenuate the beneficial effects of estradiol on LDL and TG


Menopause

Misnell 41  AJOG

Estrogen therapy by implantation of  50 mg. pellets is a safe and effective mode of therapy in cases of menopause.Long-continued administration by implantation is more economical to the patient. Pellet implantation is a simple office procedure. No untoward effects were observed in a series of 28 cases.Therapy by pellet implantation for the menopausal syndrome has proved more effective than that obtained by intramuscular injection. In patients with primary amenorrhea, complaining of lack of breast development, satisfactory results have been obtained with pellet implantation.

Greenblatt 49  AJO&G    

…implantation of hard compressed pellets of crystalline steroids resulted in a slow and more physiologic absorption of the hormone...“Since the amount of hormone released to the organism is continuous though minute in quantity, it is
conceivable that by this method the endogenous mechanism of hormonal secretion is more nearly approached and the physiologic action of the hormone more closely imitated.”

Indications for Use of Testosterone Pellets Menopausal syndrome in whom estrogen therapy has proved unsatisfactory or is contraindicated In combination with estradiol pellets in patients with uteri who have severe menopausal symptoms, in order to
prevent the untoward bleeding induced by  estrogens Dysmenorrheic patient with endometriosis or small fibroids
Fibomyomata for whom surgery is not feasible Nocturia of endocrine origin Increased libido is desired Palliative measure in patients with advanced carcinoma of the breast In combination with Desoxycorticosterone pellets for Addison’s disease

Staland 78 ActaOGS

94 women post TAH (46 BSO) treated with implant E2 20 mg every 6 months Excellent symptomatic relief 75% lasted 6 months or greater Oral estrogens were given as needed, rarely used As a rule, menopausal symptoms return when plasma oestradiol falls below 100-120 pmol/l (27-32 pg/ml).Serum FSH gives a good idea of the effect of oestrogen but need not necessarily drop despite a good effect of treatment Patients felt better with a low but constant estrogen level Very few side effects at this dose
Mastalgia in 4 patients, all over 60 yo


Brincat  84 Lancet

Prospective study 55 post men on HRT randomized to E50/T100 (33) or placebo (22) Mean number of previous implants: 6
T implants usually done for lethargy, depression, loss of libido With implant group there was improvement in all symptoms; hot flushes, palpitations, headaches, irritability, lack of concentration, insomnia, depression, aches, dyspareunia, loss of libido, lethargy No change in placebo group Return of symptoms began between 4 and 6 mos. Symptoms occur in response to a fall in oestrogen levels Offer re-implantation at 4 months


Menstrual Migraine

Magos 83  JNNP

24 patients with menstrual migraine for an average of 23.3 years Initial dose of 100 mg E2 implant with a maintenance dose of E2 50 mg. every 6.2 months (4-7 mos) 23 of 24 patients headaches improved with 20 of 24 becoming completely or almost completely headache free.


Skin health
Hormone loss at menopause has a profound influence on skin Collagen, dermal thickness and elasticity, skin water content, vascularity,  photo-protection,  wound healing and cutaneous injury repair.  Thorton 02 Hormones delivered by subcutaneous hormone implant prevent and reverse wrinkles E2 & T implants for 2-10 years; 48% increase in collagen. Brincat 83 Decrease in collagen was preventable with HRT by E2 & T pellets.  Brincat 87 Maintenance or improvement of skin collagen with E2 alone or E2 & T implants.  Brincat 87 Significantly greater collagen in women treated with SC E2 and T.  Saavas 93