Conventional
wisdom suggests, that women who have not undergone a surgical menopause,
include progesterone, or a progestin, in their hormone replacement
program to "oppose" the stimulatory effects of estrogen
on the lining of the uterus. Unfortunately, two of the most common
reasons menopausal women discontinue hormone replacement therapy programs
are associated with progesterone and progestin associated side effects.
The
challenge presented, is how to individualize a regimen, that allows
menopausal women to receive the documented health and quality of life
sustaining benefits of estrogen replacement, while both adequately
protecting the uterus and avoiding any potential progestogen-related
side effects.
What
exactly are progesterone and progestins?
Progesterone
is a naturally occurring hormone produced by the ovary following ovulation
in premenopausal women. Progestins, are synthetic products, which
mimic the effects of progesterone. The term progestogen, is used to
describe hormones that provide progesterone-like activity, and this
includes both progesterone and progestins. Although it may seem a
little confusing at first, when I am referring to both progesterone
and progestins collectively, I will use the term progestogen.
What
kind of side effects?
Many
women are intolerant to progesterone and progestins experiencing unpleasant
symptoms, ranging from mild, to severe and life altering. Other menopausal
women object to the withdrawal bleeding that may accompany progesterone
and progestin use.
In
addition, there is evidence that some progesterone, or progestin regimens
may interfere with the beneficial effects of estrogen.
Will
I definitely have unpleasant symptoms while using a progestogen?
No,
the majority of women may not experience significant symptoms while
using a progestogen. However, those women who do are often discouraged
from continuing their HRT program.
What
unpleasant symptoms can accompany progestogen use?
Unpleasant
symptoms may include irritability, fatigue, depression, diminished
libido, emotional volatility, breast tenderness, muscle aches, fluid
retention, constipation, uterine cramping, changes in appetite, headaches
and insomnia. Some women may experience none of these symptoms while
others may experience all of them.
What
kind of problems can "unopposed" estrogen stimulation cause?
"Unopposed"
estrogen administration may result in irregular and excessive vaginal
bleeding and abnormal changes of the uterine lining, including estrogen-induced
endometrial cancer. Progestogens downgrade the sensitivity of the
estrogen receptors in the uterine lining and reduce the frequency
of these problems. It is so effective in preventing excessive stimulation
of the uterine lining, that appropriate administration of progestogen,
lowers the incidence of endometrial cancer to below that of non-users
of HRT.
How
do I include a progestagen in my HRT regimen?
There
are 2 basic regimens, along with some variations.
In
the first the estrogen is given continuously and the progestogens
are taken for 10-12 days each month. In this method, after finishing
the progestogen, women using this regimen will usually have what is
referred to as "scheduled withdrawal bleeding," beginning
1-7 days after the final progestogen dose each month. This is referred
to as "sequential therapy." Some women find the bleeding
unacceptable and are less likely to continue HRT.
In
the second method, estrogen and a smaller dose of a progestogen are
combined and taken daily. This is often referred to as "continuous-combined
therapy." The rationale for this regimen is to prevent any vaginal
bleeding, but some women experience persistent spotting, or bleeding.
This regimen is available in both oral and transdermal formulations.
It is recommended by many experts and has gained wide patient and
physician acceptance in the United States.
Which
method do you recommend?
I
almost always suggest sequential HRT regimens. On the surface it might
seem more attractive to use continuous-combined therapy and avoid
any withdrawal bleeding, but this method may be less optimal than
using a progestogen for 10-12 days each month.
Why?
There
are many women who are users of continuous combined-therapy and are
happy with this regimen. They have good control of menopausal symptoms,
are not bothered by the daily progestogen dose and are able to avoid
any withdrawal bleeding. For women who consider scheduled vaginal
bleeding unacceptable and would not use HRT if it necessitated bleeding,
continuous combined therapy is likely the best option.
Nevertheless,
there is preliminary research evidence that suggests that a commonly
used oral continuous-combined HRT formulation containing conjugated
equine estrogen and medroxyprogesterone may interfere with the cardioprotective
benefits of estrogen.
In
addition, studies funded by the National Cancer Institute demonstrated
an increase in the incidence of lobular carcinoma, a relatively uncommon
form of breast cancer in patients using this formulation. The over
all increase in cancer risk appears to be small and further studies
are needed to define the issue, however for the moment, it might be
more prudent to use either sequential therapy, or a non oral formulation
of continuous-combined therapy.
There
are alternate oral continuous-combined formulations and the status
of these preparations relative to the aforementioned studies will
be addressed in ongoing and future research.
If
a woman has had a hysterectomy does she need to take a progestogen?
If
the uterus is not present, there is no need for a progestogen, natural,
or synthetic. Some make the argument that progesterone should be used
"for balance," in women without a uterus, as it more closely
resembles a woman's natural cycle. I do not recommend this as a premenopausal
woman's progesterone level is for practical purposes nearly undetectable
for most of the ovulatory cycle and there is no reason to unnecessarily
expose her to any potential negative consequences of progestogen use.
There
is one subset of women who have had a hysterectomy where progestogen
replacement would be a consideration. Those women who have had a surgical
menopause because of endometriosis and residual endometrial tissue
is known, or suspected to remain in the body. There have been a few
cases reported in the medical literature where residual endometrial
tissue has undergone malignant transformation. This is rare, but if
residual endometriosis is a consideration, 10-12 days of a progestogen
at 1-3 month intervals would be reasonable.
I
suffer from a number of the symptoms you mention while using a progestin,
is there any way to lessen the problem?
In
some, but not all cases, it is possible to diminish the impact of
these problems by changing the type, dose, schedule, or route of administration
of the progestogen, but ultimately the symptoms are a direct effect
of the progestogen, whether synthetic or natural. Many women have
fewer symptoms when using a product such as micronized progesterone,
either from a compounding pharmacy, or from the local pharmacy, where
it is sold under the name of Prometrium. Women who are allergic to
peanuts should not use this compound, as it contains peanut oil. Some
women find they experience fewer symptoms when using a progestogen
by the vaginal route, either in suppositories, or in cream form.
One
strategy that is useful is to increase the progesterone free interval
to 2, 3, or 4 months taking care to monitor for signs of endometrial
overstimulation. Some doctors have had good results with the use of
a progestin-releasing intrauterine device, which some research indicates
is capable providing endometrial protection. However, in some women
it is virtually impossible to include a progestogen in their HRT regimen
due to the severity of the negative effects. In this extreme situation,
it may be necessary to leave the progestogen out of the program entirely.
However, users of unopposed estrogen who have a uterus should be monitored
carefully, without exception, for the development of abnormal changes
of the uterine lining.
I
have heard a lot about natural progesterone skin creams, including
one that contains Yam progesterone. Is this a good thing for me to
use?
I
do not believe there is any benefit to using progesterone skin creams,
as they do not provide any protection from the long-term negative
health consequences of hormone deprivation. Yam and other plant progesterones,
cannot be metabolized in the human body, unless they are modified
pharmaceutically and any suggestion that they provide benefit, other
than skin lubrication, is without basis. Progesterone skin creams
that purport to be "natural," often contain micronized progesterone
as the active ingredient. There is one study that suggested that a
progesterone skin cream was mildly beneficial in reducing the severity
of hot flashes.
There
are those that recommend the use of progesterone skin cream as it
is "natural" and counteracts any "estrogen dominance."
However, the defining feature of menopause is ovarian failure and
its accompanying estrogen deficiency. As such, by definition, all
menopausal women are estrogen deficient and the concept that they
are suffering from "estrogen dominance," is not plausible.
These products are very effectively marketed and I believe that careful
scrutiny will reveal that a significant number of those who advocate
their use profit by their sale.
PART
1 - FINDING AN IDEAL REGIMEN... How does a woman find an HRT program
that relieves her symptoms and doesn’t cause side effects?
PART
2 - UNPLEASANT SIDE EFFECTS OF HRT… Why they occur and strategies
to avoid them.