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• Yonkers K. Review: progesterone or progestogens lead to a marginal reduction in premenstrual syndrome symptoms.  Evid Based Ment Health. 2002 May;5(2):56.
  
  The author conducted an analysis of randomized, double blind, placebo-controlled studies of progesterone or progestins in women diagnosed with PMS.  Oral micronized progesterone and the progestogens MPA, norethisterone and dydrogesterone, all showed a marginal benefit over placebo in symptom reduction.
  
  
• Shantha S, Brooks-Gunn J, Locke RJ, Warren MP. Natural vaginal progesterone is associated with minimal psychological side effects: a preliminary study. J Women Health Gend Based Med 2001 Dec;10(10):991-7.
  
  This 3 month, multicenter randomized study evaluated the psychological side effects of a vaginally applied progesterone gel in reproductive aged women treated for hypothalamic amenorrhea or premature ovarian failure. No differences were noted in psychometric measures as evaluated by the Hopkins Symptom Checklist. Natural progesterone in a vaginal gel can be an effective treatment for women requiring hormone therapy.
  
  
• Wyatt K, Dimmock P, Jones P, Obhrai M, O'Brien S. Efficacy of progesterone and progestogens in management of premenstrual syndrome: systematic review. BMJ. 2001 Oct 6;323(7316):776-80. 
  
  This systematic review of published studies of progesterone or progestogens for treatment of PMS found a small positive effect of oral micronized progesterone over placebo in the 3 trials that studied this.  No published studies of progesterone cream were found.  A statistically, but not clinically, significant improvement was seen with progestogen treatment.
  
  
• Sofuoglu M, Babb DA, Hatsukami DK. Progesterone treatment during the early follicular phase of the menstrual cycle: effects on smoking behavior in women. Pharmacol Biochem Behav 2001 May-Jun;69(1-2):299-304.
  
  In this unique randomized controlled study, administration of progesterone (200 mg oral) demonstrated a decrease in craving for and subjective effects of cigarette smoking in female smokers. With progesterone treatment, there was a noted trend to decrease smoking.
  
  
• Fitzpatrick LA, Good A. Micronized progesterone: clinical indications and comparison with current treatments. Fertil Steril 1999 Sep;72(3):389-97.
  
  The literature reviewed in this tutorial indicates a potential use for oral micronized progesterone for the treatment of secondary amenorrhea, dysfunctional uterine bleeding, luteal phase disorders, premenopausal bleeding disorders, and as a component of hormone replacement therapy that may provide a better safety profile than commonly utilized synthetic progestins.
  
  
• Massai R, Miranda P, et al. Preregistration study on the safety and contraceptive efficacy of a progesterone-releasing vaginal ring in Chilean nursing women. Contraception 1999 Jul;60(1):9-14.
  
  In this long-term controlled study, the safety and efficacy of a progesterone-releasing vaginal contraceptive device was compared to that of the copper-T 380A IUD in nursing mothers. There was no difference in breastfeeding performance or infant growth between groups. The participants using the progesterone-releasing ring had a longer period of lactational amenorrhea than did the group using the copper T. Women were tracked for over 2000 women-months of exposure in both groups. The Chilean government found the progesterone-releasing ring to be a safe and effective contraceptive alternative.
  
  
• Hajek Z, Uhlir M. [Micronized progesterone in the treatment of imminent necrosis of a myoma during pregnancy. Ultrasound changes during treatment] Ceska Gynekol 1999 Jun;64(3):189-92. [Article in Czech]
  
  Progesterone has a role in increasing blood flow to the uterus during pregnancy. As such, these researchers studied the effect of progesterone treatment to resolve imminent necrosis of a myoma in two cases. Both resolved within several days following oral and vaginal doses of progesterone (300-600 mg/day). Both women went on to deliver healthy, full-term infants.
  
  
• Pouly JL, Bassil S, Frydman R, et al. Luteal support after in-vitro fertilization: Crinone®, a sustained release vaginal progesterone gel, versus Utrogestan, an oral micronized progesterone. Human Reprod 1996;11:2085-89.
  
  90 mg of vaginal estrogen gel daily was compared to 300 mg oral progesterone daily in a randomized open-label trial of 283 IVF patients. Delivery rates, safety parameters, frequency of spontaneous abortion, ratio of newborn babies to embryo transfer were nearly identical for both groups. The oral progesterone group reported more drowsiness.
  
  
• Nappi C, Affinito P. Double-blind controlled trial of progesterone vaginal cream treatment for cyclical mastodynia in women with benign breast disease. J Endocrin Invest 1994;15(11):801-6.
  
  Eighty regularly menstruating women with mastodynia were studied to evaluate the clinical effectiveness of vaginally administered micronized progesterone. Subjects were randomly assigned to one of two groups, with all participating in a control cycle prior to treatment. One group received 4 grams of vaginal cream containing 2.5% natural progesterone for six cycles from day 19 to day 25 of the cycle. The other group was similarly treated with placebo. Both subjective reporting on a daily basis and clinical examination revealed a significant reduction in breast pain, defined as 50% reduction, in 64.9% of subjects receiving progesterone and 22.2% of subjects receiving placebo. Effects of breast nodularity were not significant. No side effects were detected.
  
  
• Martorano JT, Ahlgrimm M, Meyers D. Differentiating between natural progesterone and synthetic progestogens: clinical implications for PMS management. Comprehensive Therapy 1993; 19(3):96-8.
  
  Clinical observations demonstrate that patients suffering from PMS respond to treatment with natural progesterone, whereas synthetic progestins may exacerbate the condition. The authors review the differences between natural progesterone and synthetic progestins.
  
  
• Saarikoski S, Yliskoski M, Penttila I. Sequential use of norethisterone and natural progesterone in pre-menopausal bleeding disorders. Maturitas 1990 Jun;12(2):89-97.
  
  This randomized controlled study evaluated the effects of norethisterone (NET) and micronized progesterone (MP) on bleeding disorders in pre-menopausal women. 80 patients were randomized to the trial and all were found via endometrial morphology to need progestogen therapy. They were subsequently treated with NET or MP. In both treatment groups, hyperplastic changes disappeared during the first three cycles, with the duration of treatment being 6 months. NET decreased follicle-stimulating hormone, luteinizing hormone, estradiol and sex-hormone-binding globulin levels (P < 0.001) whereas no changes were seen during MP treatment. High-density-lipoprotein cholesterol and triglyceride levels were also lowered by NET (P< 0.001-0.02) slightly decreased phospholipids. MP treatment had no effect on lipid profiles suggesting it may be a preferred progestogen for the treatment of bleeding disorders.
  
  
• Sitruk-Ware R, Bricaire C, De Lignieres B, Yaneva H, Mauvais-Jarvis P. Oral micronized progesterone. Bioavailability pharmacokinetics, pharmacological and therapeutic implications--a review. Contraception 1987 Oct; 36(4): 373-402.
  
  This paper reviews the effects and benefits of oral micronized progesterone. Progesterone exhibits anti-estrogenic effects, anti-androgenic effects, and anti-mineralocorticoid effects in addition to its progestational effects. No side effects have been reported for micronized progesterone with respect to lipid profile, coagulation, or blood pressure, leading the authors to recommend micronized progesterone as suitable for treatment of PMS, menopause, irregular cycles, and pregnancy maintenance.
  
  
• Dennerstein L, Spencer-Gardner C, Gotts G, Brown JB, Smith MA, Burrows GD. Progesterone and the premenstrual syndrome: a double blind crossover trial. Br Med J (Clin Res Ed) 1985 Jun 1; 290(6482): 1617-21.
  
  In this double-blind, placebo-controlled, randomized, crossover trial, oral micronized progesterone demonstrated effectiveness in alleviating premenstrual complaints. Twenty-three women completed a Beck, et al depression inventory, Moos’s menstrual distress questionnaire, Spielberger, et al state anxiety inventory, and daily symptom diary before and during each treatment. There was an overall benefit of treatment for all variables, except positive moods, restlessness, and interest in sex. For most parameters, maximum benefit was seen within the first month of treatment, demonstrating an effectiveness of progesterone as a viable treatment option for women with PMS.
  
  
• Ferre F, Uzan M, Janssens Y, Tanguy G, Jolivet A, Breuiller M, Sureau C, Cedard L. Oral administration of micronized natural progesterone in late human pregnancy. Effects on progesterone and estrogen concentrations in the plasma, placenta, and myometrium. Am J Obstet Gynecol 1984 Jan 1; 148(1): 26-34.
  
  Levels of progesterone, 17 beta-estradiol, and estrone were measured in the plasma, in the placenta, and at different sites in myometrium following a single dose of micronized oral progesterone administered to 15 pregnant women immediately prior to elective cesarean section.  In comparison to a control group, progesterone levels in the treated women increased in the plasma and myometrium 150 minutes after administration. Placenta progesterone levels did not demonstrate any change. No change was seen in 17 beta-estradiol levels in the plasma or the myometrium, however placental levels were increased. Estrone levels were decreased in the myometrium and in the placenta, and unchanged in the plasma.
  
  
• Dalton K. The effects of progesterone and progestogens on the foetus. Neuropharmacology 1981; 20:1267-9.
  
  This article looks at the differing effects of progesterone and synthetic progestogens on the fetus. Of note in this article is evidence that progesterone supplementation may reduce episodes of pre-eclampsia. Synthetic progestogen supplementation during pregnancy may produce a variety of side effects. Several references are made to articles documenting cases of masculinization of external genitalia in female babies. There are two known cases of true hermaphroditism and several cases of behavioral problems developing in adolescent girls whose mothers took oral synthetic progestogens during pregnancy. More problematic may be administration of oral estrogen-progestogen preparations. Side effects may include spina bifida, esophageal anomalies, heart defects and limb reduction deformities.
  
  
• Dalton K. Prenatal progesterone and educational attainments. British Journal of Psychiatry 1976; 126:438-42.
  
  This study compares educational attainments of 34 children whose mothers received prenatal progesterone with 37 normal and 12 toxemic controls. Results at ages 17-24 showed that progesterone children were more likely to continue schooling after 16 years, a higher number left school with ‘O’ and ‘A’ level grades and more obtained entrance to university. The best academic results were found for children whose mothers had received over 5 grams of progesterone for a minimum of eight weeks, with treatment beginning before week sixteen.