Download Estrogen-Based Hormone Replacement Therapy

Women’s Health/Pharmacology
and thus can be useful for
women with significant
liver dysfunction or hypertriglyceridemia.4
The vaginal route is
absorbed well systemically, but may be prescribed
to alleviate urogenital
symptoms.
HRT is contraindicated
in patients experiencing pregnancy, unexplained vaginal bleeding, active or chronic
liver disease, active deep vein thrombosis and
history of breast or endometrial cancer.4,5
Relative contraindications include hypertriglyceridemia, history of thromboembolic
disease, family history of breast cancer, gallbladder disease, migraine headaches, uterine
leiomyoma, and seizure disorder.4 While these
are not absolute contraindications, risks vs.
benefits must be discussed with the patient
before prescribing HRT.
Whether or not HRT should be used is a
controversial question in general, and the
ongoing debate is not within the focus of this
article.
Estrogen Replacement
A number of estrogen compounds are
derived from diverse sources, each having
unique actions at the tissue level. Estradiol-17
beta (E2) is the most frequently used steroid
hormone of the estrogen group and is
released from the premenopausal ovary.
Estrone-E1 increases naturally at menopause,
and estriol (E3) is a weaker compound that
naturally increases during pregnancy. The lat-
ter two are only in compounded medications
such as Tri-Estrogen or Tri-Est. Estradiol is
chemically synthesized to estradiol-17 beta
and can be prepared from the sterols present
in certain plants, such as Mexican yams or
soybeans.
Estrogen has many positive effects when
used alone as replacement therapy (Tables 1
and 2). Medications used for vaginal atrophy
increase vaginal lubrication, decrease vaginal
atrophy, increase pelvic blood flow, and alleviate dysparenuia.
In addition, estrogen alone can decrease
low-density lipoproteins (LDL) and increase
high-density lipoproteins (HDL) and triglycerides in the first year of treatment.5 Estrogen
administration during and following
menopause can substantially reduce the rate
Table 1
Estrogen-Based Hormone Replacement Therapy
PRODUCT (marketer)
Premarin (Wyeth-Ayerst)
ESTROGEN
Oral conjugated equine
estrogen
COMMON DAILY DOSE (MG)
0.625 mg
Estrace (Mead Johnson)
Estradiol (Watson Labs)
Oral micronized estradiol
1.0 mg
Estraderm (Ciba-Geigy)
Climara (Berlex)
Alora (PBG Pharm)
FemPatch (Parke-Davis)
Vivelle (Novartis)
Vivelle-Dot (Novartis)
Esclim (Women First Healthcare)
Generic Available
(.05 & .1)
Transdermal
estradiol-17 beta
Estraderm, Alora, Vivelle,
Vivelle- Dot, Esclim (change
patch twice weekly)
Estratab (Solvay)
Menest (SmithKline Beecham)
Oral esterfied estrogen
0.625
Ogen (Abbott)
Generic Available
Oral estropipate
0.625
Cenestin (Duramed)
Oral synthetic conjugated
estrogens
0.625
Estinyl (Schering)
Oral ethinyl estradiol
Vagifem (Pharmacia)
Estradiol vaginal tablet (with
applicator)
58
Climara and FemPatch
(change patch weekly)
ADVANCE for Nurse Practitioners • June 2002
Initial: 1 tab qd x 2 weeks
Maintenance: twice weekly
AVAILABLE DOSES (MG)
0.3
0.625
0.9
1.25
2.5
0.5
1.0
2.0
COST
# 30s
$15-44
Estraderm: 0.05, 0.1
Climara: 0.025, 0.05, 0.075, 0.1
Alora: 0.05, 0.075, 0.1
Fempatch: 0.025
Vivelle: 0.0375, 0.05, 0.075, 0.1
Vivelle-Dot: 0.0375, 0.05,
0.075, 0.1
Esclim: 0.025, 0.0375,
0.05, 0.075, 0.1
1 box = $18-30
Estraderm, Alora, Vivelle,
Vivelle-Dot and Esclim
contain 8 patches/box;
Climara and FemPatch
contain 4 patches/box
0.3 (Estratab & Menest)
0.625 (Estratab & Menest)
1.25 (Menest only)
LV (Menest only)
0.625
1.25
2.5
0.625
0.9
1.25
0.02
0.05
25 mcg
#30s
$9-29
#30s
$6-22
(Generic)
#30s
$23-54
$10-20
#30s
$18-23
$12-20
1 box (15 tabs)
$36.52
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Women’s Health/Pharmacology
Table 2
Vaginal Hormone Replacement Therapy
PRODUCT (marketer)
Premarin (Wyeth-Ayerst)
ESTROGEN
Conjugated equine
estrogen vaginal cream
0.625 mg/g
Estropipate cream
1.5 mg/g
Ogen Vaginal (Pharmacia & Upjohn)
PROGESTIN
Progesterone cream
4%, 8%
Estradiol vaginal cream
0.1 mg/g
Estring (Bristol Myers Scquibb)
Estradiol vaginal ring
2.0 mg
0.01% dienestrol cream
Ortho Dienestrol Vaginal Cream
COST
$51.62
(42.5-g tube)
Administer cyclically;
3 weeks on, 1 week off
Crinone (Wyeth-Ayerst)
Estrace Vaginal (Bristol Myers Scquibb)
DOSAGE*
Administer cyclically;
3 weeks on, 1 week off
(Ortho Pharm.)
*Dosages can vary according to prescribers and patient needs.
$48.28
(42.5-g tube)
4%-6 tubes, $30;
18 tubes, $88.63
8%-6 tubes, $59.38;
18 tubes, $171.40
2-4 g/day for 1-2 weeks.
$39.34
Gradually reduce to 1⁄2 initial (42.5-g tube)
dosage. Maintenance dose
1 g q.d.-t.i.d.
Change q 3 months
$76.00
1 Box
Administer cyclically.
$30.71 (78 g tube)
1 or 2 applicators/day for
1 or 2 weeks, then reduce to
1
⁄2 initial dosage.
Maintenance dose of
one applicator
1 to 3 times/week
Table 3
Combination HRT
PRODUCT (marketer)
Premphase (Wyeth-Ayerst)
Prempro (Wyeth-Ayerst)
Combipatch (Rhone-Poulenc Rorer)
(Apply patch twice weekly)
Femhrt (Pfizer)
Orthoprefest (Ortho-McNeil)
Activella (Pharmacia & Upjohn)
ESTROGEN
Oral conjugated equine estrogen, 0.625 mg
Oral conjugated equine estrogen, 0.625 mg
Transdermal estradiol, 0.05 mg
PROGESTIN
Medroxyprogesterone, 5 mg (14 days/28-day cycle)
Medroxyprogesterone, 2.5 mg or 5.0 mg q.d.
Norethindrone acetate, 0.14 mg or 0.25 mg q.d.
COST
$29
$29
$31-$33/ box of 8
Oral ethinyl estradiol, 0.05 mg
Oral estradiol, 1.0 mg
Oral estradiol, 1.0 mg
Norethindrone acetate, 1.0 mg
Norgestimate*, 0.09 mg
Norethindrone acetate, 0.5 mg
$22
$25
$25
*Nonandrogenic Progestins
Table 4
Progestin-Only HRT
PRODUCT (marketer)
PROGESTIN
Provera (Pharmacia & Upjohn)
Cycrin (Wyeth-Ayerst) 2.5, 5, 10 mg
Amen (Carnrick) 10 mg
Generic Available 2.5, 5, 10 mg
Prometrium (Schering-Plough)
Micronor (Ortho) .35 mg
Nor-QD (Syntex) .35 mg
Oral
medroxyprogesterone
acetate
Oral micronized progesterone
Oral norethindrone
CYCLIC REGIMEN
10-14 days/mo (mg)
5 or 10
CONTINOUS REGIMEN
(daily) (mg)
2.5
200
0.7-1.0
100-200
0.35
COST
$23-30
$8-9 (Generic)
$23-41
$32
$31
Table 5
Estrogen-Androgen HRT
60
Oral
Oral
ESTROGEN (mg)
1.25 mg esterified estrogen
0.625 mg esterified estrogen
ADVANCE for Nurse Practitioners • June 2002
METHYLTESTOSTERONE (mg)
2.5
1.25
COST
$37.46
$30.09
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∆
PRODUCT (marketer)
Estratest (Solvay Pharmaceuticals Inc.)
Estratest HS (Solvay Pharmaceuticals Inc.)
Women’s Health/Pharmacology
of osteoporotic bone loss,
decrease the incidence of
hip and vertebral fracture
by 50%, and improve
bone density measurements.6
The sum of estrogen’s
multiple effects on neural
functions suggests an
antidepressant effect that
improves mood and behavior.6,8 Because of a
lack of supporting clinical evidence, however, estrogen should not be considered an
adequate antidepressant for woman with a
major mood disorder.1
The most frequently prescribed HRT product is conjugated equine estrogen (CEE), a
multiple component formulation.
The effects of some of the individual com-
ponents are widely known and serve as a
gold standard for menopause symptom treatment.
The efficacy of this product, however,
results from the sum of its components even
though not all are fully characterized. For this
reason, CEE is not reproducible in a generic
form. It is important to note equivalent doses
of estrogen when prescribing HRT. A daily
CEE dose of 0.625 mg is comparable to 1 mg
estradiol, 5 µg of ethinyl estradiol (synthetic),
0.05 mg transdermal biweekly, and 0.625 synthetic conjugated phytoestrogen.9
Progesterone Replacement
In addition to E2, the premenopausal ovary
secretes other steroid hormones, such as
progesterone and androgens. To prevent
endometrial hyperplasia in women who have
a uterus, progesterone is given along with
Figure 1
Classification of Progestins in Oral Contraceptives
PROGESTINS
17-acetoprogesterone
19-nortestosterone
Estranes
Gonanes
Medroxyprogesterone acetate (MPA)
Norethindrone
Norgestrel
Megestrol
Norethindrone acetate (NETA)
Levonorgestrel
Ethynodiol diacetate
Norgestimate (NGM)
Lynestrenol*
Gestodene*
Norethynodrel*
Desogestrel
Pregnanes
*Not available in United States
Reproduced with permission from Elsevier Science, based on: Carr BR. Uniqueness of oral contraceptive progestins. Contraception.
1998;58(suppl 3):23S-27S.
Figure 2
Other Hormone Replacements
DHEA (dehydroepiandrosterone)
25 mg daily – women Side effects: acne, hirsutism
50 mg daily – men
Pregnenolone (parent steroid compound)
10 - 20 mg/day
Cholesterol
Side effects: drowsiness
Pregnenolone
Progesterone
DHEA
Androstenedione
Testosterone
Estriol, estrone, estradiol
Sahelian R. Pregnenolone: Nature’s Feel Good Hormone. Garden City Park, N.Y.: Avery Publishing Group; 1997: 18.
62
ADVANCE for Nurse Practitioners • June 2002
estrogen for hormone replacement therapy
(Tables 3 and 4). The most common and
widely prescribed progestin is medroxyprogesterone acetate (MPA). It has historically
been the least expensive and most potent
progestin and was added to the HRT regimen
in the late 1970s.
The most common side effects of progestins include breast pain, mood changes,
headache, appetite changes and bloating.
These side effects seem to be related to the
progesterone preparation used, the dosage
ratio of progesterone to estrogen, and the use
of cyclic vs. continuous progesterone. 6,7
Additionally, MPA counteracts the increase in
HDL produced by estrogen.4
New progestins developed in the 1980s
were chemical entities called estranes and
gonanes (Figure 1). These second- and thirdgeneration progestins have less androgenic
activity and minimize androgenic side effects
while still offering endometrial protection.
Micronized progesterone has been available since late 1998 as Prometrium. This
progesterone is synthesized through an emulsified process and does not counteract the
positive effects of HDL produced by
estrogen.4
Micronized progesterone capsules contain
peanut oil and are thus contraindicated for
patients with a peanut allergy. The most common side effect of this medication is drowsiness, so it is often better tolerated when
dosed at nighttime.
Androgen Replacement
Adding an androgen to replacement therapy can improve well-being and sexual function (Table 5). Testosterone contributes to
overall muscle function and tone, energy and
vitality, and sexual desire, arousal and orgasm
in women. After menopause, total androgen
production drops 50% in women with intact
ovaries and more than 50% in women who
undergo bilateral oophorectomy.10 Sources of
circulating testosterone in postmenopausal
women are the adrenal glands (25%), ovaries
(25%) and peripheral conversion of
androstenedione (50%).
Reports of androgen administration in surgically postmenopausal women indicate positive effects on libido, sexual performance and
well-being.10,11 Dose-related side effects associated with androgen use in women include
acne, hirsutism, voice changes, weight gain
and undesirable lipid profile changes.7,10
Lowering the androgen dose may prevent
these side effects.
Other Hormone Replacements
Pregnenolone is an active metabolite of
progesterone and dehydroepiandrosterone
(DHEA) (Figure 2), which are considered
neuroactive steroids and are available as a
Continued on page 102
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