Cyclogest® (micronised progesterone) FAQs
- Hormonal actions: induces secretory transformation of the endometrium
- Stabilises the endometrium.
- Stimulates the growth of the uterus.
- Maintains uterine quiescence by stabilising lysosomal membranes.
- Inhibits myometrial contractions.
- Inhibits tissue rejection by modulation the immune system.
- Protects the conceptus.
It is important to take Cyclogest® pessaries at the same time each day in order to have a stable dose and to achieve a successful treatment.5 If your patient forgets to insert a pessary, they should do so as soon as they remember, unless it is nearly time for the next dose. It is not recommend to use two doses together. It is important to remember to use the remaining doses at the correct time.6
The pessary may be inserted into either the vagina or rectum (back passage) depending upon certain other conditions.
Your patient should insert Cyclogest® into the:
- vagina if they have:
- colitis (inflammation of the colon causing frequent attacks of diarrhoea).
- problems controlling their bowel movements (faecal incontinence).
- rectum (back passage) if they have:
- a vaginal infection (discharge from their vagina).
- regular cystitis (a burning pain on. passing water)
- recently given birth.
- to use a barrier method of birth control such as a diaphragm, cap or condom. Such devices may not work properly in the presence of the hard fat from the pessary.
According to a Cyclogest® study,7 female patients received a single dose of Cyclogest® 400mg administered vaginally or rectally respectively on two separate occasions during the follicular phase of the menstrual cycle. Serum progesterone was measured, and it was found that the amount of progesterone absorbed by each route was similar.
Following vaginal dosing the progesterone plasma levels reached a plateau and were sustained at the plateau for a duration of ~24 h. After rectal administration higher peak plasma levels were achieved but the plasma concentrations remained elevated for a shorter period of ~10 h. Much greater inter-subject variability was noted after rectal administration.
However, we are unable to give advice on personal medical matters. HCPs should decide which is the best route of administration for their patients based on individual circumstances. Please discuss with your patient any concerns that they might have regarding administering Cyclogest® vaginally or rectally.
Cyclogest® will be prescribed to reflect an individual patient’s personal medical history and circumstance. In some cases, patients might need more progesterone during IVF treatment, but they might not need to continue Cyclogest® once foetal heartbeat is confirmed.8 However, some patients might need more progesterone during early pregnancy weeks because of early pregnancy bleeding with previous history of miscarriage.9 Furthermore, some patients might need extra progesterone to prevent preterm birth.10
We are unable to give advice on personal medical matters; initiating or stopping any medication should be a decision made by HCPs based on your patient’s individual circumstances. In summary, please always refer to national guidelines about when to start, how to use, and when to end Cyclogest®.
Researchers at Tommy’s National Centre for Miscarriage Research inform that giving vaginal progesterone to women with early pregnancy bleeding and a history of miscarriage could lead to 8,450 more babies being born each year in the UK.11
The team have published two studies evidencing both the scientific and economic advantages of giving a course of self-administered twice daily vaginal progesterone pessaries to women from when they first present with early pregnancy bleeding up until 16 weeks of pregnancy to prevent miscarriage.12,13
Vaginal progesterone is a hormone that is naturally secreted by the ovaries and placenta in early pregnancy and is vital to the attainment and maintenance of healthy pregnancies.
Based on evidence from recent clinical trials, clinicians are already adopting the guidelines and are offering micronised vaginal progesterone as standard treatment in the NHS for women with early pregnancy bleeding and a history of miscarriage.
There is a growing body of research which has found that micronised vaginal progesterone is both cost-effective and can increase a woman’s chances of having a baby.
Whilst we cannot recommend use of Cyclogest® that is not included on the Summary of Product Characteristics (SmPC), we can confirm that Cyclogest® contains “natural micronised vaginal progesterone”, the same molecule used in the above-mentioned studies.
L.D. Collins is actively supporting trials to investigate the optimum use of Cyclogest®, providing HCPs and patients with guidance and advice on how the product should be best used. Unfortunately, we are unable to give advice on personal medical matters. This medicine should be used as it is recommended by the national guidelines and as directed in the Cyclogest® SmPC. Please refer to NICE guideline NG156 about infertility and recent publications about serum progesterone levels14 if you would like more clarification on how much Cyclogest® you need to use.
There is a wide margin of safety with Cyclogest® pessaries, but overdosage may produce euphoria or dysmenorrhoea. Progesterone is likely to be well tolerated in overdose. Levels of progesterone during pregnancy are up to 100-fold higher than during normal menstrual cycle, although levels increase gradually over the course of pregnancy.15
Oral dosages of progesterone of up to 3,600 mg/day have been assessed in clinical trials, with the main side effect being sedation.16 There is a case report of progesterone misuse with an oral dosage of 6,400 mg/day.17 Bioavailability studies performed with Cyclogest® (Data on file) confirms that there is a limit to maximum absorption by vaginal administration which is 1600mg/day. Any higher dose administered vaginally will not be absorbed, hence the risk of overdose is very low.20
Always recommend patients to wash their hands before and after inserting a Cyclogest® pessary.
To insert into the vagina, patients need to place the pessary between the lips of the vagina and push the pessary upwards and backwards. They may find it easier to do this if they are lying down or squatting.
To insert into the rectum (back passage), patients should gently push the Cyclogest® pessary into the rectum for about one inch. The muscles help to ensure the pessary when it is in far enough. Squeezing buttocks together for a few seconds will ensure that the pessary does not come out.
Please refer to section 3 of the patient information leaflet (PIL), “How to use Cyclogest®”, which accompanies the product and gives more information on how to use Cyclogest®. Unfortunately, we are unable to give any further information on how to use the product other than the information as stated in the PIL.
Constipation is a potential side effect of Cyclogest® usage in patients undergoing ART treatment.6 Khrouf et al18 compared Cyclogest® administered rectally and vaginally and saw an increase in constipation when used rectally in contrast to vaginal administration of progesterone. Given this is a common side effect of Cyclogest® usage, patients should be reassured that constipation is common. However, we recommend that any patient who experiences adverse events as a result of using our product should consult their prescribing doctor to discuss their treatment options further. Patients can also report side effects directly via the Yellow Card Scheme at: https://yellowcard.mhra.gov.uk/ or via the Yellow Card app, which can be downloaded from the Apple App Store, or Google Play Store.
The available technical data shows that Cyclogest® pessaries melt in 15 minutes at 35–39°C after vaginal administration.
The “Cyclogest® study F3521” compared the pharmacokinetics of Cyclogest® after two different routes of administration (vaginal and rectal).
The progesterone plasma profiles obtained from vaginal administration showed sustained release characteristics. After vaginal administration the plasma levels of progesterone increased steadily from a mean pre-treatment value to reach a plateau concentration by 2.5 hours after dosing. Peak levels were reached between 2.5 and 24 hours and the plasma progesterone levels remained elevated at the plateau until 24 hours after dosing and subsequently declined to reach pre-dose concentrations by 72 hours post dose.
Cyclogest® is suitable for vegan and vegetarians. This is certified with the Vegan Society. There is no use of material of human or animal origin in the manufacture of Cyclogest®; therefore the contents of Cyclogest® can be considered suitable for vegans and vegetarians.
Progesterone used in Cyclogest® is obtained from plant sources, mainly from
Mexican yam (Dioscorea Mexicana or Cabeza De Negro).
The source of the hard fat (Suppocire® BS2) used in Cyclogest® is of a vegetable origin which is made up of three components: hydrogenated palm kernel oil, hydrogenated palm oil, and glycerol which are derived from palm, palm kernel, coconut, corn, or rapeseed.19
The active pharmaceutical ingredient, progesterone, is produced by a semi-synthetic process using a crude mixture of vegetable/plant sterols. The plant soy sterols used to manufacture the starting materials for the active pharmaceutical ingredients (APIs) and intermediates are not proteins and therefore are not classified as “soy allergens”.
Unfortunately, we are not able to advise whether the product is suitable for a patient with a soy allergy, but the HCP may use the information regarding the source of ingredients to assess whether the product is suitable for their patient based on their allergies/intolerances.
Yes, Cyclogest® pessaries are considered suitable for Halal consumers because the contents of the pessary are all of vegetable origin. The pessaries contain natural progesterone and hard fat both of which are of vegetable origin. There is no use of materials from human or animal origin in the manufacture of Cyclogest® pessaries’.
-
- a history of previous Pre-Term Birth before 34 weeks of pregnancy or
- late miscarriage after 16 weeks of pregnancy, or
- short cervical length <25mm measured with ultrasound between week 16 -24 of pregnancy. Natural Progesterone is crucial for the maintenance of pregnancy because it relaxes the uterine muscles and prevents uterine contractions. There is good evidence that vaginal progesterone reduces the risk of Pre-Term Birth before 34 weeks. (UK NICE Guideline NG25)
One pack of Cyclogest® contains 15 pessaries in strips of laminated PVC.
- Hormonal actions: induces secretory transformation of the endometrium
- Stabilises the endometrium.
- Stimulates the growth of the uterus.
- Maintains uterine quiescence by stabilising lysosomal membranes.
- Inhibits myometrial contractions.
- Inhibits tissue rejection by modulation the immune system.
- Protects the conceptus.
It is important to take Cyclogest® pessaries at the same time each day in order to have a stable dose and to achieve a successful treatment.5 If your patient forgets to insert a pessary, they should do so as soon as they remember, unless it is nearly time for the next dose. It is not recommend to use two doses together. It is important to remember to use the remaining doses at the correct time.6
The pessary may be inserted into either the vagina or rectum (back passage) depending upon certain other conditions.
Your patient should insert Cyclogest® into the:
- vagina if they have:
- colitis (inflammation of the colon causing frequent attacks of diarrhoea).
- problems controlling their bowel movements (faecal incontinence).
- rectum (back passage) if they have:
- a vaginal infection (discharge from their vagina).
- regular cystitis (a burning pain on. passing water)
- recently given birth.
- to use a barrier method of birth control such as a diaphragm, cap or condom. Such devices may not work properly in the presence of the hard fat from the pessary.
According to a Cyclogest® study,7 female patients received a single dose of Cyclogest® 400mg administered vaginally or rectally respectively on two separate occasions during the follicular phase of the menstrual cycle. Serum progesterone was measured, and it was found that the amount of progesterone absorbed by each route was similar.
Following vaginal dosing the progesterone plasma levels reached a plateau and were sustained at the plateau for a duration of ~24 h. After rectal administration higher peak plasma levels were achieved but the plasma concentrations remained elevated for a shorter period of ~10 h. Much greater inter-subject variability was noted after rectal administration.
However, we are unable to give advice on personal medical matters. HCPs should decide which is the best route of administration for their patients based on individual circumstances. Please discuss with your patient any concerns that they might have regarding administering Cyclogest® vaginally or rectally.
Cyclogest® will be prescribed to reflect an individual patient’s personal medical history and circumstance. In some cases, patients might need more progesterone during IVF treatment, but they might not need to continue Cyclogest® once foetal heartbeat is confirmed.8 However, some patients might need more progesterone during early pregnancy weeks because of early pregnancy bleeding with previous history of miscarriage.9 Furthermore, some patients might need extra progesterone to prevent preterm birth.10
We are unable to give advice on personal medical matters; initiating or stopping any medication should be a decision made by HCPs based on your patient’s individual circumstances. In summary, please always refer to national guidelines about when to start, how to use, and when to end Cyclogest®.
Researchers at Tommy’s National Centre for Miscarriage Research inform that giving vaginal progesterone to women with early pregnancy bleeding and a history of miscarriage could lead to 8,450 more babies being born each year in the UK.11
The team have published two studies evidencing both the scientific and economic advantages of giving a course of self-administered twice daily vaginal progesterone pessaries to women from when they first present with early pregnancy bleeding up until 16 weeks of pregnancy to prevent miscarriage.12,13
Vaginal progesterone is a hormone that is naturally secreted by the ovaries and placenta in early pregnancy and is vital to the attainment and maintenance of healthy pregnancies.
Based on evidence from recent clinical trials, clinicians are already adopting the guidelines and are offering micronised vaginal progesterone as standard treatment in the NHS for women with early pregnancy bleeding and a history of miscarriage.
There is a growing body of research which has found that micronised vaginal progesterone is both cost-effective and can increase a woman’s chances of having a baby.
Whilst we cannot recommend use of Cyclogest® that is not included on the Summary of Product Characteristics (SmPC), we can confirm that Cyclogest® contains “natural micronised vaginal progesterone”, the same molecule used in the above-mentioned studies.
L.D. Collins is actively supporting trials to investigate the optimum use of Cyclogest®, providing HCPs and patients with guidance and advice on how the product should be best used. Unfortunately, we are unable to give advice on personal medical matters. This medicine should be used as it is recommended by the national guidelines and as directed in the Cyclogest® SmPC. Please refer to NICE guideline NG156 about infertility and recent publications about serum progesterone levels14 if you would like more clarification on how much Cyclogest® you need to use.
There is a wide margin of safety with Cyclogest® pessaries, but overdosage may produce euphoria or dysmenorrhoea. Progesterone is likely to be well tolerated in overdose. Levels of progesterone during pregnancy are up to 100-fold higher than during normal menstrual cycle, although levels increase gradually over the course of pregnancy.15
Oral dosages of progesterone of up to 3,600 mg/day have been assessed in clinical trials, with the main side effect being sedation.16 There is a case report of progesterone misuse with an oral dosage of 6,400 mg/day.17 Bioavailability studies performed with Cyclogest® (Data on file) confirms that there is a limit to maximum absorption by vaginal administration which is 1600mg/day. Any higher dose administered vaginally will not be absorbed, hence the risk of overdose is very low.20
Always recommend patients to wash their hands before and after inserting a Cyclogest® pessary.
To insert into the vagina, patients need to place the pessary between the lips of the vagina and push the pessary upwards and backwards. They may find it easier to do this if they are lying down or squatting.
To insert into the rectum (back passage), patients should gently push the Cyclogest® pessary into the rectum for about one inch. The muscles help to ensure the pessary when it is in far enough. Squeezing buttocks together for a few seconds will ensure that the pessary does not come out.
Please refer to section 3 of the patient information leaflet (PIL), “How to use Cyclogest®”, which accompanies the product and gives more information on how to use Cyclogest®. Unfortunately, we are unable to give any further information on how to use the product other than the information as stated in the PIL.
Constipation is a potential side effect of Cyclogest® usage in patients undergoing ART treatment.6 Khrouf et al18 compared Cyclogest® administered rectally and vaginally and saw an increase in constipation when used rectally in contrast to vaginal administration of progesterone. Given this is a common side effect of Cyclogest® usage, patients should be reassured that constipation is common. However, we recommend that any patient who experiences adverse events as a result of using our product should consult their prescribing doctor to discuss their treatment options further. Patients can also report side effects directly via the Yellow Card Scheme at: https://yellowcard.mhra.gov.uk/ or via the Yellow Card app, which can be downloaded from the Apple App Store, or Google Play Store.
The available technical data shows that Cyclogest® pessaries melt in 15 minutes at 35–39°C after vaginal administration.
The “Cyclogest® study F3521” compared the pharmacokinetics of Cyclogest® after two different routes of administration (vaginal and rectal).
The progesterone plasma profiles obtained from vaginal administration showed sustained release characteristics. After vaginal administration the plasma levels of progesterone increased steadily from a mean pre-treatment value to reach a plateau concentration by 2.5 hours after dosing. Peak levels were reached between 2.5 and 24 hours and the plasma progesterone levels remained elevated at the plateau until 24 hours after dosing and subsequently declined to reach pre-dose concentrations by 72 hours post dose.
Cyclogest® is suitable for vegan and vegetarians. This is certified with the Vegan Society. There is no use of material of human or animal origin in the manufacture of Cyclogest®; therefore the contents of Cyclogest® can be considered suitable for vegans and vegetarians.
Progesterone used in Cyclogest® is obtained from plant sources, mainly from
Mexican yam (Dioscorea Mexicana or Cabeza De Negro).
The source of the hard fat (Suppocire® BS2) used in Cyclogest® is of a vegetable origin which is made up of three components: hydrogenated palm kernel oil, hydrogenated palm oil, and glycerol which are derived from palm, palm kernel, coconut, corn, or rapeseed.19
The active pharmaceutical ingredient, progesterone, is produced by a semi-synthetic process using a crude mixture of vegetable/plant sterols. The plant soy sterols used to manufacture the starting materials for the active pharmaceutical ingredients (APIs) and intermediates are not proteins and therefore are not classified as “soy allergens”.
Unfortunately, we are not able to advise whether the product is suitable for a patient with a soy allergy, but the HCP may use the information regarding the source of ingredients to assess whether the product is suitable for their patient based on their allergies/intolerances.
Yes, Cyclogest® pessaries are considered suitable for Halal consumers because the contents of the pessary are all of vegetable origin. The pessaries contain natural progesterone and hard fat both of which are of vegetable origin. There is no use of materials from human or animal origin in the manufacture of Cyclogest® pessaries’.
-
- a history of previous Pre-Term Birth before 34 weeks of pregnancy or
- late miscarriage after 16 weeks of pregnancy, or
- short cervical length <25mm measured with ultrasound between week 16 -24 of pregnancy. Natural Progesterone is crucial for the maintenance of pregnancy because it relaxes the uterine muscles and prevents uterine contractions. There is good evidence that vaginal progesterone reduces the risk of Pre-Term Birth before 34 weeks. (UK NICE Guideline NG25)
One pack of Cyclogest® contains 15 pessaries in strips of laminated PVC.
- Saunders H, Khan C, D’Hooghe T, Magnúsdóttir TB, Klingmann I, Hrafnsdóttir S. Efficacy, safety and tolerability of progesterone vaginal pessaries versus progesterone vaginal gel for luteal phase support after in vitro fertilisation: a randomised controlled trial. Human Reproduction 2020;35:355-363. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048710/ [Last accessed: December 2023].
- Mesen TB, Young SL. Progesterone and the Luteal Phase: A Requisite to Reproduction. Obstetrics and Gynecology Clinics of North America 2015;42:135-151. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0889854514000965?via%3Dihub [Last accessed: December 2023].
- van der Linden M, Buckingham K, Farquhar C, Kremer JAM, Metwally M. Luteal phase support for assisted reproduction cycles. Cochrane Database of Systematic Reviews 2015. Available at: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009154.pub3/full [Last accessed: December].
- Malik S, Krishnaprasad K. Natural Micronized Progesterone Sustained Release (SR) and Luteal Phase: Role Redefined!! Journal of Clinical & Diagnostic Research 2016;10:QE01-QE04. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800604/ (Last accessed: December 2023].
- Duijkers IJM, Klingmann I, Prinz R, Hrafnsdottir S, Magnusdottir ThB, Klipping C. Effect on endometrial histology and pharmacokinetics of different dose regimens of progesterone vaginal pessaries, in comparison with progesterone vaginal gel and placebo. Human Reproduction 2018;33:2131-2140. Available at: https://academic.oup.com/humrep/article/33/11/2131/5108541 [Last accessed: December 2023].
- Cyclogest 400mg pessaries Patient Information Leaflet. Available at: https://www.medicines.org.uk/emc/product/5569/pil#gref [Last accessed: December 2023].
- L.D. Collins. Data on file.
- National Institute for Health and Care Excellence. Fertility problems: assessment and treatment, 2013. Available at: https://www.nice.org.uk/guidance/cg156 [Last accessed: December 2023].
- National Institute for Health and Care Excellence. Ectopic pregnancy and miscarriage: diagnosis and initial management, 2019. Available at: https://www.nice.org.uk/guidance/ng126 [Last accessed: December 2023].
- National Institute for Health and Care Excellence. Preterm labour and birth, 2015. Available at: https://www.nice.org.uk/guidance/ng25 [Last accessed: December 2023].
- Tommy’s. Giving some pregnant women progesterone could prevent 8,450 miscarriages a year, says experts, 2020. Available at: https://www.tommys.org/about-us/charity-news/giving-some-pregnant-women-progesterone-could-prevent-8450-miscarriages-year-say-experts [Last accessed: December 2023].
- Coomarasamy A, Williams H, Truchanowicz E, Seed PT, Small R, Quenby S, Gupta P, Dawood F, Koot YEM, Bender Atik R, Bloemenkamp KWM, Brady R, Briley AL, Cavallaro R, Cheong YC, Chu JJ, Eapen A, Ewies A, Hock A, Kaaijk EM, Koks CAM, Li T-C, Maclean M, Mol BW, Moore J, Ross JA, Sharpe L, Stewart J, Vaithilingam N, Farquharson RG, Kilby MD, Khalaf Y, Goddiin M, Regan L, Rai R. A Randomised Trial of Progesterone in Women with Recurrent Miscarriages. The New England Journal of Medicine 2015;373:2141-2148. Available at: https://www.nejm.org/doi/full/10.1056/nejmoa1504927 [Last accessed: December 2023].
- Okeke Ogwulu CB, Goranitis I, Devall AJ, Cheed V, Gallos ID, Middleton LJ, Harb HM, Williams HM, Eapen A, Daniels JP, Ahmed A, Bender-Atik R, Bhatia K, Bottomley C, Brewin J, Choudhary M, Deb S, Duncan WC, Ewer AK, Hinshaw K, Holland T, Izzat F, Johns J, Lumsden M, Manda P, Norman JE, Nunes N, Overton CE, Kriedt K, Quenby S, Rao S, Ross J, Shahid A, Underwood M, Vaithilingham N, Watkins L, Wykes C, Horne AW, Jurkovic D, Coomarasamy A, Roberts TE. The cost-effectiveness of progesterone inpreventing miscarriages in women with earlypregnancy bleeding: an economic evaluationbased on the PRISM trial. BJOG 2020;127:757-767. Available at: https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/1471-0528.16068 [Last accessed: July 2022].
- Labarta E, Mariani G, Paolelli S, Rodriguez-Varela C, Vidal C, Giles J, Bellver J, Cruz F, Marzal A, Celada P, Olmo I, Alamá P, Remohi J, Bosch E. Impact of low serum progesterone levels on the day of embryo transfer on pregnancy outcome: a prospective cohort study in artificial cycles with vaginal progesterone. Human Reproduction 2021;36:683-692. Available at: https://pubmed.ncbi.nlm.nih.gov/33340402/ [Last accessed: July 2022].
- University of Rochester Medical Center. Health Encyclopedia: Progesterone. Available at: https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=167&ContentID=progesterone [Last accessed: July 2022].
- Schweizer E, Case WG, Garcia-Espana F, Rickels K, Greenblatt DJ. Progesterone co-administration in patients discontinuing long-term benzodiazepine therapy: effects on withdrawal severity and taper outcome. Psychopharmacology 1995;117:424–429. Available at: https://link.springer.com/article/10.1007/BF02246214 [Last accessed: December 2023].
- Keefe DL, Sarrel P. Dependency on progesterone in woman with self-diagnosed premenstrual syndrome. Lancet 1996;347:1182. Available at: https://pubmed.ncbi.nlm.nih.gov/8609776/ [Last accessed: December 2023].
- Khrouf M, Slimani S, Khrouf MR, Braham M, Bouyahia M, Berjeb KK, Chaabane HE, Merdassi G, Kaffel AZ, Zhioua A, Zhioua F. Progesterone for Luteal Phase Support in In Vitro Fertilization: Comparison of Vaginal and Rectal Pessaries to Vaginal Capsules: A Randomized Controlled Study. Clinical Medicine Insights: Women’s Health 2017;9:43-47. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217976/ [Last accessed: April 2022].
- Suppocire® BS2X. Available at: https://www.gattefosse.com/pharmaceuticals-products/suppocire-bs2x [Last accessed: December 2023].
- Cyclogest Dose Linearity study F.36 Clinical Pharmacology Department, Hoechst UK Ltd, Milton Keynes, UK (Dec 1990 Data on File)
- Cyclogest STUDY NO.: F. 35 COMPARISON OF THE PHACOKINETICS AFTER TWO DIFFERENT ROUTES OF ADMINISTRATION. Clinical Pharmacology Department, Hoechst UK Ltd, Mil ton Keynes, UK (Jan 1990 Data on File)
- https://www.nice.org.uk/guidance/ng25/chapter/Recommendations#care-of-women-at-risk-of-preterm-labour