Ovarian failure at the menopause is associated with cessation of
progesterone production as well as oestrogen deficiency.
Some people advocate the use of natural
progesterone cream for the relief of menopausal
symptoms. There are few proper studies of
natural progesterone cream. It is not a natural
product but in common with most sex hormone
treatments it is synthesised . Proponents of the
cream believe that menopausal symptoms are due
not to oestrogen deficiency but to an imbalance
between oestrogen and progesterone. The theory
known as 'oestrogen dominance' is that there is
a relative excess of oestrogen is produced:
women aged over 35 may not ovulate every month
and because progesterone is not produced in non-ovulatory
cycles there is relatively more oestrogen in the
body; similarly, after the menopause virtually
no progesterone is produced but the body still
produces some oestrogen.
An American physician, Dr Lee, has described and publicised his experience with ‘natural
progesterone cream – ‘Progest’ - which is applied to the skin. The
progesterone is produced in the laboratory from diosgenin by extraction from the Mexican Yam. Many other reproductive hormones are similarly extracted from the Mexican Yam. A variety of clinical benefits have been claimed including increased bone density, relief of benign breast disease symptoms, enhanced libido (sex drive
Q 28.18) and relief of premenstrual syndrome. Dr Lee recognises the fact that others have used
progesterone in capsule form or rectal suppositories (Cyclogest) but he found that the transdermal route was more acceptable for his patients. There is some evidence that
progesterone may have benefit on the heart. Controlled studies are required to confirm the possible advantages of Progest.
It has been claimed that progesterone is very
well absorbed through the skin when it is in a
properly formulated bio-identical natural
progesterone cream, and unlike orally taken
progesterone it is not intercepted by the liver.
For this reason cream dosage is quite small. One recent study, at King’s
College Hospital
in London
, found that Progest resulted in only a small increase in plasma progesterone levels and the authors commented that they were not convinced that this was likely to achieve a biological effect. Transdermal
progesterone (40 mg) per day for 42 days
produced a small increase in serum progesterone
concentration, although there was wide
variation. Whether such levels are potentially
of clinical benefit remains to be proven.0001
In one study, seventy-seven percent of women
preferred the CEE (combined equine estrogen)/PC
(progesterone cream) to the CEE/MPA (medroxyprogesterone
tablets) (P<.001). Of the 52 post-treatment
endometrial biopsies: 40 revealed atrophic
endometrium and 12 proliferative endometrium (7
in the oral progestin group and 5 in the PC
group). There was no evidence of endometrial
hyperplasia in any of the specimens. The
incidence of vaginal spotting was similar in
both groups. It was concluded that patients
preferred transdermal progesterone cream over
oral MPA.0502
This preliminary data indicate that CEE/PC has a
similar effect on the endometrium as standard
oral HT over a 6-month period.
In another
study, however, the dose of natural progesterone
cream was insufficient to fully attenuate the mitogenic effect of oestrogen on the
endometrium. The authors concluded that they
would not recommend this combination of hormones
to be used by postmenopausal women.0503
Given the current best available evidence, using
progesterone cream for postmenopausal therapy
regimens should be considered as an incompletely
substantiated treatment option, and its clinical
applications should perhaps be restricted to
well-designed interventional trials that assess
its efficacy and safety.0701
Several patients have come to me wishing to continue Progest
progesterone cream having commenced it under the supervision of others. There have been many occasions when patients have not had their symptoms adequately controlled by oestrogen replacement therapy and Progest has apparently helped a few of them.
Progesterone Suppositories
Progesterone suppositories contain progesterone in a wax
base. Progesterone suppositories are suspended in a base not
unlike cocoa butter and they are inserted into the vagina,
allowing for the drug to target the uterus.
Upon insertion, the
warmth of the body causes the suppository to melt and
release the progesterone.
Unfortunately, the suppositories can create some discomfort
due to their discharge, and some people question the
progesterone’s effective following insertion. They provide consistent, even absorption. When used
vaginally, many women complain of leakage that occurs. When
used rectally, some patients report bowel stimulation.
Natural and synthetic progesterone have been used to
treat luteal insufficiency, premenstrual syndrome, and in
infertile patients. The transvaginal route has advantages,
such as lack of local pain, avoidance of first-pass hepatic
metabolism, rapid absorption, high bioavailability and local
endometrial effect. In a study of vaginally administered
progesterone in the follicular phase of the menstrual cycle
has shown that levels of progesterone are similar to those
obtained in ovulatory and luteal phases. The progesterone
regimen for adequate endometrial protection and in vitro
fertilization (IVF) programs still remains to be determined.0401
Progesterone suppositories are often used to support the
endometrium in IVF programs. There was no difference in
perineal irritation after progesterone suppositories or
propgesterone 8% gel although significantly more patients
found inconvenience of administration, leaking out and
interference with coitus after the suppositories. Another
study compared side effects and patient convenience of
vaginal progesterone suppositories (Cyclogest) and vaginal
progesterone tablets (Endometrin) used for luteal phase
support in in vitro fertilization/embryo transfer (IVF/ET)
cycles. There was no difference in perineal irritation after
the use of Cyclogest suppositories or Endometrin tablets but
more patients found administration of Endometrin tablets
difficult.
Dr Dalton in the UK championed the use of progesterone
suppositories in the management of PMS8701
although the validity of this therapy has been challenged.8601,
9001 To further investigate the efficacy of
progesterone in the treatment of the symptoms of
premenstrual syndrome (PMS), Baker et al9501
studied its effects on 25 subjects diagnosed with
moderate to severe PMS. In addition, each subject was
interviewed by a psychiatrist on a monthly basis. Hormone
assays demonstrated no differences between treatment and
control groups. A significant improvement was found in
symptoms relating to tension, mood swings, irritability,
anxiety and lack of control. It was concluded that
metabolites of progesterone (pregnanolone and
allopregnanolone) may play a physiologic role as anxiolytic
agents, perhaps modifying mood and anxiety and that
study confirms the utility of twice daily, 200-mg
progesterone vaginal suppositories, in the alleviation of
some PMS symptoms relating to anxiety and irritability.
Related Medical Abstracts - Click on the paper title:-
Progesterone Gel
Progesterone vaginal gel can
be successfully used as an alternative to intramuscular
progesterone for luteal support in IVF. One daily dose
appears sufficient to induce clinical pregnancies and live
births at a rate comparable to intramuscular
supplementation.0801
The efficacy and tolerability of two different types of
vaginal progesterone, Crinone 8% gel (Fleet Laboratories
Ltd., Watford, United Kingdom) and Utrogestan capsules
(Laboratories Besins International, Paris, France), used for
luteal support after in vitro fertilization (IVF) cycles was
compared.0703
The efficacy of the two vaginal formulations was nearly the
same, but the tolerability and acceptability of Crinone 8%
gel were superior, in the opinion of patients.
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