Is there a place for progesterone replacement?

Ovarian failure at the menopause is associated with cessation of progesterone production as well as oestrogen deficiency.

"Natural" Progesterone Cream

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 inLondon , 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 e quine 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.

Related Medical Abstracts - Click on the paper title:-

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 progesterone 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.


Women's Health

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Women's Health

This is the personal website of David A Viniker MD FRCOG, retired Consultant Obstetrician and Gynaecologist - Specialist Interests - Reproductive Medicine including Infertility, PCOS, PMS, Menopause and HRT.
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I do hope that you find the answers to your women's health questions in the patient information and medical advice provided.


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