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Progesterone
What is it?
Progesterone is one of the many hormones produced by a woman’s body.
Progesterone is produced by the ovaries and helps to regulate the menstrual cycle and is necessary to sustain a pregnancy.
Progesterone is produced naturally in the body. There are also several
synthetic forms of progesterone, called progestins, which are manufactured
and are not found naturally in the human body. Progestins are the type of
progesterone found in most commercially available products used for hormone replacement therapy (HRT) and contraception.
How is progesterone different from the progestins?
Unlike progesterone, progestins are commercially prepared contain chemicals that are not identical to those made naturally by the human body.
Because of this, progestins may cause different side effects than progesterone.
Progestin
Synthetic progestins increase LDL (bad) cholesterol and decrease HDL (good) cholesterol and can
lead to an increased risk of developing atherosclerosis.
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Other side effects of synthetic progestins include abdominal bloating, breast discomfort, headache,
depression, weight gain, and acne.
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R E P O R T
Case Report: Hydroxyprogesterone Caproate Injection for Prevention of Preterm Labor
From the International Journal of
Pharmaceutical Compounding 2006;
10(3); 172.
Shannon W. Fields, BA, CPhT
Innovative Pharmacy Solutions
Edmond, Oklahoma
A 32-year-old woman presented at 24 weeks’ gestation in preterm labor and was admitted to a local
hospital for observation. Further examination by
her obstetrician revealed that her cervix had shortened and she was experiencing contractions. The
patient, a registered nurse, was in good overall
health, though the pregnancy was considered high
risk because of her obstetric history.
The patient’s history included a pregnancy at age
20, which ended in a loss of the fetus at 28 weeks’
gestation. A second pregnancy at age 23 ended in
a loss of the fetus at 38 weeks’ gestation. Both of
these fetuses had multiple birth defects. A third
pregnancy at age 27 ended in the premature delivery of a daughter at 28 weeks’ gestation. The baby
did well, despite a birth weight of 2 pounds 11
ounces, and came home after spending several
weeks in the neonatal intensive care unit. A fourth
pregnancy at age 30 ended in the delivery of
another healthy daughter at 35 weeks, but the
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PROGESTERONE
CONTINUED
Progesterone
Progesterone is better at preventing menopausal
changes in cholesterol, including LDL and
HDL.
a large-scale study involving thousands of
women on HRT. In July of 2002, one part of this
trial was ended prematurely by the researchers
conducting the trial because of the increase in
incidence of several undesirable endpoints in
women taking the hormones versus women who
were taking placebo. This part of the study
looked at women taking a combination of conjugated estrogens and progestin. Neither conjugated estrogens nor progestins are found naturally in a woman’s body, but they are the active
ingredients in several prescription hormone
replacement preparations. This part of the study
showed an increased risk of cardiovascular events
such as strokes and heart attacks, increased risk
of dementia, and an increase in problems with
breast cancer detection by mammography in the
women who were taking the hormones.
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Progesterone causes less liver dysfunction, breast
tenderness, and fluid retention, and a lower incidence of headache than progestins.
The only significant side effect associated with
progesterone is drowsiness.
Recent clinical trials suggest that progestins may
also have a detrimental effect on overall health,
including increased incidence of cardiovascular
disease and dementia. While progesterone has
not been included in many of these studies, studies that do involve progesterone indicate that
progesterone may not have the same detrimental
effects as progestins.
HOW DO CLINICAL TRIALS OF HRT APPLY TO
PROGESTERONE?
❖ Most clinical trials study progestins, hormones
available in commercial products that are not
always the same hormones that are produced
naturally by a woman’s body.
❖ The Postmenopausal Estrogen/Progestin
CASE REPORT
CONTINUED
It is important to remember that progesterone
was not involved in the WHI trial, so we cannot
say that these increased risks would also apply to
progesterone.
WHO SHOULD AVOID TAKING
PROGESTERONE?
❖ Patients with any of the following:
• Breast or reproductive organ cancers
• Undiagnosed vaginal bleeding
• High risk for arterial disease
• Allergy to progesterone
• Major depression
• Liver disease
• Pregnancy (although some women with low
natural levels of progesterone may be given
progesterone during pregnancy)
WHAT ARE THE AVAILABLE DOSAGE FORMS
OF PROGESTERONE?
❖ Sublingual troches (lozenges that melt in the
mouth)
❖ Vaginal suppository
❖ Oral capsules, tablets, and suspension
❖ Topical cream or gel
❖ Injection
WHAT CAN COMPOUNDING PHARMACISTS
PROVIDE PER PHYSICIAN PRESCRIPTION?
Natural progesterone is used by compounding
pharmacists to formulate various dosage forms of
bioidentical hormone replacement therapy
(BHRT). It offers a safer, more natural alternative to synthetic progestins used in HRT.
Only one commercial preparation (Prometrium)
contains natural progesterone; it is available only
as capsules in only two doses and contains peanut
oil. Women who require different dosage forms
or strengths or have an
allergy to peanut oil can
benefit from the flexibility
and expertise of working
with a physician and compounding pharmacist to
prepare an individualized
formulation. For example,
women who cannot tolerate oral progesterone may
benefit from topical
administration or a vaginal
suppository.
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Interventions (PEPI) trial, published in 1995,
studied women taking estrogen alone, estrogen
plus progesterone, or estrogen plus a progestin.
In this trial, researchers determined that women
taking estrogen alone had an improved cholesterol profile compared to when they began the
estrogen. Women taking estrogen and progesterone did not experience a significantly different effect on cholesterol than the women taking
estrogen alone. Women taking estrogen and a
progestin, however, did not have as much of an
improved effect on cholesterol, suggesting that
progestins may have an adverse effect on cardiovascular outcomes.
• Diabetes mellitus
• Epilepsy
• Kidney dysfunction
• Migraines
❖ The Women’s Health Initiative (WHI) trial is
❖ Patients with the following diseases may experience fluid retention from progesterone:
• Asthma
• Cardiovascular disease
tion for this preparation is provided in the
International Journal of Pharmaceutical
Compounding.1
The patient continued on her medication until
preterm labor recurred at 27 weeks’ gestation, at
which point she was readmitted to the hospital.
She was given magnesium sulfate during her stay
to stop her contractions, and was monitored for
2 nights prior to being discharged. Procardia
(Nifedipine) 5 mg every 6 hours was added to
her regimen of terbutaline and hydroxyprogesterone caproate. Strict bed rest was continued.
The patient continued working on a parttime basis during her fifth pregnancy until
preterm labor was diagnosed at 24 weeks.
Upon her discharge from the hospital, she
was placed on strict bed rest. The patient
was prescribed terbutaline 5 mg every 6
hours, and was referred to a local compounding pharmacy for hydroxyprogesterone caproate 250-mg/mL injections.
Instructions were to inject 1 mL (250 mg)
intramuscularly once weekly. The formula-
At 30 weeks of pregnancy, Procardia
(Nifedipine) was discontinued. The patient was
monitored by her physician via ultrasound every
4 weeks and given a nonstress test twice weekly.
The patient continued her regimen of weekly
hydroxyprogesterone caproate injections and
terbutaline 5 mg as needed. Her cervix had not
shortened any further as of her last examination
before going into labor. At 36 weeks of pregnancy, all medications were discontinued. The
patient delivered at 36.5 weeks’ gestation with an
apparently healthy 6-pound baby boy.
Suggested Reading and Resources
1. Fields SW. Case Report; Hydorxyprogesterone
caproate injection for preventention of preterm
labor. IJPC 2006; 10(3) 172.
• Meis PJ. Society for Maternal-Fetal Medicine. 17
hydroxyprogesterone for the prevention of preterm
delivery. Obstet Gynecol 2005; 105(5 Pt 1):
1128–1135.
• Sexton DJ, O’Reilly MW, Friel AM et al.
Functional effects of 17 alpha-hydroxyprogesterone
RxTriad-A publication of the International Journal of Pharmaceutical Compounding. © 2006 IJPC. All rights reserved.
FROM THE LITERATURE
Reed-Kane D, Kirschbaum K. Prevention of
preterm delivery with compounded 17a–hydroxprogesterone caproate. IJPC 2006; 10(3):
165–171.
ABSTRACT
17a–hydroxyprogesterone caproate is a naturally occurring metabolite of progesterone
that is produced in significant quantities
during pregnancy. The demand for
17a–hydroxyprogesterone caproate, the
lack of a commercially available manufactured form approved by the US Food and
Drug Administration, and publication of the
results of a large trial to determine the effectiveness of the drug in the prevention of
preterm delivery have spawned an increased
interest in compounded formulations of the
drug. The demand also has necessitated a
review of the available literature and of past
clinical studies, and a look at present and
planned studies. Owing to the importance
of this drug in pregnancy and the need for
safety, accuracy in potency, and sterility in
an intramuscular injection (the most common route of administration), compounding
pharmacies must be in compliance with the
United States Pharmacopeia Chapter <797>
standards should they wish to compound
this formulation.
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final 8 weeks of pregnancy were spent on bed
rest—a precaution taken mostly because of the
woman’s gestational history.
caproate (17P) on human myometrial contractility
in vitro. Reprod Biol Endocrinol 2004; 2(1): 80