Major research findings

Progesterone has been reported to prevent sleep disturbances and modulate GH, TSH, and melatonin secretion in postmenopausal women. 11 . Administration of progesterone has been shown to affect sleep architecture and hormone profiles, particularly improving sleep quality in women with sleep disturbances. 11 . Progesterone not only alleviates sleep disturbances but also promotes GH secretion and suppresses TSH secretion. 11 . These results suggest that progesterone may be a potential therapeutic option for improving sleep quality.

Progesterone has been reported to show mild sedative effects in postmenopausal women after a single dose. 5 . In addition, progesterone can cause mild sedative effects and mood changes in women with normal menstrual cycles. 5 . Progesterone administration can affect mood, sexual behavior, and sleep patterns, but these effects are often mild and vary from person to person., 9 .

Progesterone has also been shown to increase the frequency of contractions in human term myometrial strips. 3 . This contradicts the idea that progesterone suppresses uterine contractions during pregnancy, leading to easier contractions during labor. 3 . Progesterone administration could affect the contraction pattern of uterine smooth muscle, influencing the labor process. 3 .

Progesterone has been shown to be administered intranasally to alleviate sleep disturbances in postmenopausal women. 14 . Intranasal administration may provide better bioavailability of progesterone than oral administration, making it a more effective treatment option. 14 . Progesterone can provide a new option for treating sleep disorders. 14 .

Progesterone can potentially potentiate the effects of benzodiazepines like triazolam. 12 . This is believed to be due to progesterone acting on GABA(A) receptors, enhancing the effects of benzodiazepines. 12 . Progesterone can also exacerbate the side effects of benzodiazepines. 12 .

Progesterone has been shown to act directly on the endometrium when administered vaginally. 4 . Despite low plasma progesterone levels, vaginal administration results in secretory transformation of the endometrium. 4 . This suggests that progesterone can directly affect the endometrium, achieving its effects even with low plasma concentrations. 4 .

Progesterone has been suggested to have therapeutic effects in tobacco use disorder (TUD), with women benefiting more than men. 16 . The conversion of progesterone to the neurosteroid allopregnanolone is hypothesized to partly explain these therapeutic effects, but this has not been clinically investigated. 16 . Progesterone could potentially aid in treating nicotine withdrawal symptoms in smokers. 16 .

Progesterone has been reported to produce mild sedative effects in both men and women. 8 . Progesterone administration can lead to increased heart rate, increased fatigue, and impaired smooth eye pursuit. 8 . While progesterone administration can cause mild side effects, these are usually temporary. 8 .

Prenatal progesterone treatment has been suggested to potentially have long-term effects on child development, behavior, and health, but these effects are unclear. 15 . Progesterone administration is used to prevent premature birth, but further research is needed to understand its long-term effects on children. 15 .

Different administration routes for progesterone have been shown to result in different metabolic patterns. 2 . Oral administration has been reported to lead to higher ratios of 5α- and 5β-pregnanolone/progesterone plasma concentrations compared to vaginal administration. 2 . As 5α- and 5β-pregnanolone are known to have psychotropic effects, oral and vaginal administration of progesterone have different indications and precautions. 2 .

Progesterone could improve endothelial function in postmenopausal women. 13 . Progesterone is known to be an effective treatment for hot flushes and night sweats, common symptoms in postmenopausal women. 13 . Progesterone administration can affect endothelial function, weight, blood pressure, metabolism, lipids, inflammation, and coagulation. 13 .

Progesterone has been shown not to inhibit estrogen-induced nitric oxide production. 10 . Progesterone does not hinder the positive effects of estrogen on endothelial function in postmenopausal women. 10 . Progesterone may be advantageous over medroxyprogesterone acetate in improving endothelial function in postmenopausal women undergoing hormone therapy. 10 .

Combining progesterone with estrogen therapy can improve sleep patterns in postmenopausal women. 9 . Progesterone, when combined with estrogen, has been shown to be more effective than estrogen alone in reducing sleep disturbances like periodic limb movement, hot flashes, and bruxism. 9 . Progesterone can also help reduce symptoms like sleep arousals, anxiety, and memory impairment. 9 .

Progesterone receptor modulators have the potential to be used therapeutically in progesterone-dependent conditions like endometriosis, fibroids, and labor induction. 7 . CDB-2914 is a synthetic steroid that binds to both progesterone and glucocorticoid receptors. 7 . CDB-2914 has shown antiprogestational activity in animal experiments, with effects seen at doses 50 times lower than those required for antiglucocorticoid effects. 7 .

Vaginal micronized progesterone can be used in continuous hormone replacement therapy for postmenopausal women. 6 . In postmenopausal women who have not had a hysterectomy, it is essential to co-administer a progestogen with estrogen therapy to counteract the estrogenic proliferative effect on the endometrium. 6 . The dosage and administration route of progestins can affect their metabolic and tissue effects. 6 .

Benefits and Risks

Benefit Summary

Progesterone can help improve sleep disturbances, hot flashes, sweating in postmenopausal women, enhance endothelial function, and boost GH secretion. 11 , 9 , 13 . Progesterone may also be effective in alleviating nicotine withdrawal symptoms in smokers. 16 .

Risk Summary

Progesterone can cause mild sedative effects, mood changes, increased heart rate, increased fatigue, and impaired smooth eye pursuit. 5 , 8 . Progesterone can also enhance the effects of benzodiazepines, potentially increasing the risk of side effects. 12 . Progesterone administration during pregnancy may have long-term effects on the development, behavior, and health of children. 15 .

Comparison between Studies

Commonalities in Studies

Many studies have shown that progesterone can be effective in improving symptoms like sleep disturbances, hot flashes, and sweating in postmenopausal women. 11 , 9 . Studies also suggest that progesterone may improve endothelial function. 13 , 10 . Progesterone has the potential to improve overall health in postmenopausal women.

Differences in Studies

The effects of progesterone can vary depending on factors such as dosage, administration route, and the specific population studied. Additionally, while progesterone can cause mild side effects, the severity can vary from person to person. 5 , 8 , 2 . Further research is needed to thoroughly understand the safety and effectiveness of progesterone.

Consistency and Contradictions in Results

Progesterone has been shown to be effective in improving sleep disturbances in postmenopausal women. 11 , 14 . However, progesterone has also been shown to increase the frequency of contractions in uterine smooth muscle, potentially affecting the labor process. 3 . Caution should be taken when administering progesterone to pregnant women.

Considerations for Real-World Application

Progesterone can potentially improve symptoms like sleep disturbances, hot flashes, and sweating in postmenopausal women. 11 , 9 . However, progesterone can cause mild side effects and is not recommended for pregnant women. 5 , 8 . Using progesterone should be done cautiously, in consultation with a doctor.

Limitations of Current Research

Research on the safety and effectiveness of progesterone is still limited. More research is needed, particularly concerning the effects of progesterone on pregnant women and its long-term effects. 15 . There are also many unknowns regarding the long-term effects of progesterone.

Future Research Directions

Further research is needed on the safety and effectiveness of progesterone. Specifically, research should focus on the effects of progesterone on pregnant women, its long-term effects, and determining optimal dosages and administration routes. 15 . Additionally, research is needed to investigate the interactions between progesterone and other hormones.

Conclusion

Progesterone has the potential to improve symptoms like sleep disturbances, hot flashes, and sweating in postmenopausal women. 11 , 9 . However, progesterone can cause mild side effects and is not recommended for pregnant women. 5 , 8 . Using progesterone should be done cautiously, in consultation with a doctor. Further research is needed on the safety and effectiveness of progesterone.