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'''Estrone/progesterone''' ('''E1/P4'''), sold under the brand name '''Synergon''', is a [[combination drug|combination medication formulation]] of [[estrone (medication)|estrone]], an [[estrogen (medication)|estrogen]], and [[progesterone (medication)|progesterone]], a [[progestogen]]. E1/P4 is used as an [[injection (medicine)|injectable]] preparation to induce [[withdrawal bleeding]] in women with non-[[pregnancy]]-related [[amenorrhea]] (absence of [[menstruation]]).<ref name="Synergon-Leaflet">{{cite web | url = https://serp.mc/wp-content/uploads/2018/05/synergon.pdf | title = Synergon label }}</ref><ref name="Drugs.com-E2">{{cite web |url= https://www.drugs.com/international/estrone.html |title=Estrone |website=Drugs.com |access-date=2019-04-12 |archive-date=2018-06-21 |archive-url= https://web.archive.org/web/20180621143924/https://www.drugs.com/international/estrone.html |url-status=dead }}</ref><ref name="Drugs.com-P4">{{cite web |url= https://www.drugs.com/international/progesterone.html |title=Progesterone|website=Drugs.com|access-date=2019-04-12}}</ref><ref name="Martindale2009">{{cite book | veditors = Sweetman SC |chapter=Sex hormones and their modulators |title=Martindale: The Complete Drug Reference |edition=36th |year=2009 |pages=2101, 2127 |publisher=Pharmaceutical Press |location=London|isbn=978-0-85369-840-1|quote=Estrone [...] Progesterone [...] Multi-ingredient: [...] Fr.: Synergon [...] Turk.: Synergon}}</ref>
'''Estrone/progesterone''' ('''E1/P4'''), sold under the brand name '''Synergon''', is a [[combination drug|combination medication formulation]] of [[estrone (medication)|estrone]], an [[estrogen (medication)|estrogen]], and [[progesterone (medication)|progesterone]], a [[progestogen]]. E1/P4 is used as an [[injection (medicine)|injectable]] preparation to induce [[withdrawal bleeding]] in women with non-[[pregnancy]]-related [[amenorrhea]] (absence of [[menstruation]]).<ref name="Synergon-Leaflet">{{cite web | url = https://serp.mc/wp-content/uploads/2018/05/synergon.pdf | title = Synergon label }}</ref><ref name="Drugs.com-E2">{{cite web |url= https://www.drugs.com/international/estrone.html |title=Estrone |website=Drugs.com |access-date=2019-04-12 |archive-date=2018-06-21 |archive-url= https://web.archive.org/web/20180621143924/https://www.drugs.com/international/estrone.html |url-status=dead }}</ref><ref name="Drugs.com-P4">{{cite web |url= https://www.drugs.com/international/progesterone.html |title=Progesterone|website=Drugs.com|access-date=2019-04-12}}</ref><ref name="Martindale2009">{{cite book | veditors = Sweetman SC |chapter=Sex hormones and their modulators |title=Martindale: The Complete Drug Reference |edition=36th |year=2009 |pages=2101, 2127 |publisher=Pharmaceutical Press |location=London|isbn=978-0-85369-840-1|quote=Estrone [...] Progesterone [...] Multi-ingredient: [...] Fr.: Synergon [...] Turk.: Synergon}}</ref>
<ref name="pmid19232600">{{cite journal | vauthors = Addo VN, Tagoe-Darko ED | title = Knowledge, practices, and attitudes regarding emergency contraception among students at a university in Ghana | journal = International Journal of Gynaecology and Obstetrics | volume = 105 | issue = 3 | pages = 206–209 | date = June 2009 | pmid = 19232600 | doi = 10.1016/j.ijgo.2009.01.008 | quote = Synergon, a combination of progesterone and oestrone in an injectable form, is marketed to induce withdrawal bleeding in women with nongravid amenorrhea; however, it can be used as an arbortifacient [11]. | s2cid = 22216977 }}</ref><ref name="pmid17634106">{{cite journal | vauthors = Kongnyuy EJ, Ngassa P, Fomulu N, Wiysonge CS, Kouam L, Doh AS | title = A survey of knowledge, attitudes and practice of emergency contraception among university students in Cameroon | journal = BMC Emergency Medicine | volume = 7 | pages = 7 | date = July 2007 | pmid = 17634106 | pmc = 1933435 | doi = 10.1186/1471-227X-7-7 | quote = Synergon is dedicated product made up of a combination of progesterone and oestrone in an injectable form. It is used to induce withdrawal bleeding in cases of non-gravid amenorrhoea. In Cameroon, synergon is widely used among students as an abortifacient and is usually administered clandestinely by nurses when a woman presents with amenorrhoea. Such an attitude stemmed from the fact that this product induces withdrawal bleeding, so that some cases of amenorrhoea falsely believed to be due pregnancy are resolved by one or a few intramuscular injections of Synergon. We are not aware of similar findings reported from other countries. Synergon is not produced by the manufacturer as an abortifacient; how it came to be associated with abortion in Cameroon is not known. It is also not known whether it actually induces abortion or it only induces withdrawal bleeding in women with non-gravid amenorrhoea. }}</ref><ref>{{cite journal | vauthors = Romero R, Nicolaides KH, Conde-Agudelo A, O'Brien JM, Cetingoz E, Da Fonseca E, Creasy GW, Hassan SS | display-authors = 6 | title = Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study | journal = Ultrasound in Obstetrics & Gynecology | volume = 48 | issue = 3 | pages = 308–317 | date = September 2016 | pmid = 27444208 | pmc = 5053235 | doi = 10.1002/uog.15953 }}</ref> It has also sometimes been used [[off-label]] as an [[abortifacient]].<ref name="pmid19232600" /><ref name="pmid17634106" /><ref name="pmid29104024">{{cite journal | vauthors = Baxerres C, Boko I, Konkobo A, Ouattara F, Guillaume A | title = Abortion in two francophone African countries: a study of whether women have begun to use misoprostol in Benin and Burkina Faso | journal = Contraception | volume = 97 | issue = 2 | pages = 130–136 | date = February 2018 | pmid = 29104024 | doi = 10.1016/j.contraception.2017.10.011 | quote = It is not hard to find [abortion] services in Cotonou [Benin]. [...] The most commonly used method was [manual vacuum aspiration], followed by curettage, and more rarely a Synergon® (progesterone + estrone) injection, a product indicated in the symptomatic treatment of non-gravid amenorrhea.8 | doi-access = free }}</ref> The medication comes in a three-[[ampoule]] pack, contains 1&nbsp;mg estrone and 10&nbsp;mg progesterone per [[ampoule]], and is administered by [[intramuscular injection]].<ref name="Synergon-Leaflet" /><ref name="pmid19232600" /><ref name="pmid17634106" /><ref name="McDonnell1986">{{cite book| vauthors = McDonnell K |title=Adverse Effects: Women and the Pharmaceutical Industry|url=https://books.google.com/books?id=SgA-AAAAYAAJ|year=1986|publisher=International Organization of Consumers Unions, Regional Office for Asia and the Pacific|isbn=978-967-9973-17-4|page=15|quote=Synergon. 10 mg progesterone. 1 mg folliculine [estrone].}}</ref> The usual dose of the medication is three injections, each two days apart, with the treatment duration not exceeding one week.<ref name="Synergon-Leaflet" /> E1/P4 is or has been available in [[France]], [[Monaco]], and [[Turkey]], as well as in some [[francophone|French-speaking]] [[Africa]]n countries such as [[Benin]] and [[Cameroon]].<ref name="Drugs.com-E2" /><ref name="Drugs.com-P4" /><ref name="Martindale2009" /><ref name="Micromedex">{{cite web | url = https://www.ndrugs.com/?s=synergon#doctor_indications | title = Synergon Indications | work = Generic Drugs | publisher = ndrugs.com }}</ref><ref name="pmid17634106" /><ref name="pmid29104024" /> The medication has been marketed since at least 1952.<ref name="Endokrinologie1952">{{cite book|title=Endokrinologie|url=https://books.google.com/books?id=5dUgAQAAMAAJ|year=1952|publisher=Johann Ambrosius Barth Verlag.|quote=Synergon. Progesterone + Follikulin [Estrone]. Amp. Lab. Hépat.}}</ref>
<ref name="pmid19232600">{{cite journal | vauthors = Addo VN, Tagoe-Darko ED | title = Knowledge, practices, and attitudes regarding emergency contraception among students at a university in Ghana | journal = International Journal of Gynaecology and Obstetrics | volume = 105 | issue = 3 | pages = 206–209 | date = June 2009 | pmid = 19232600 | doi = 10.1016/j.ijgo.2009.01.008 | quote = Synergon, a combination of progesterone and oestrone in an injectable form, is marketed to induce withdrawal bleeding in women with nongravid amenorrhea; however, it can be used as an arbortifacient [11]. | s2cid = 22216977 }}</ref><ref name="pmid17634106">{{cite journal | vauthors = Kongnyuy EJ, Ngassa P, Fomulu N, Wiysonge CS, Kouam L, Doh AS | title = A survey of knowledge, attitudes and practice of emergency contraception among university students in Cameroon | journal = BMC Emergency Medicine | volume = 7 | pages = 7 | date = July 2007 | pmid = 17634106 | pmc = 1933435 | doi = 10.1186/1471-227X-7-7 | quote = Synergon is dedicated product made up of a combination of progesterone and oestrone in an injectable form. It is used to induce withdrawal bleeding in cases of non-gravid amenorrhoea. In Cameroon, synergon is widely used among students as an abortifacient and is usually administered clandestinely by nurses when a woman presents with amenorrhoea. Such an attitude stemmed from the fact that this product induces withdrawal bleeding, so that some cases of amenorrhoea falsely believed to be due pregnancy are resolved by one or a few intramuscular injections of Synergon. We are not aware of similar findings reported from other countries. Synergon is not produced by the manufacturer as an abortifacient; how it came to be associated with abortion in Cameroon is not known. It is also not known whether it actually induces abortion or it only induces withdrawal bleeding in women with non-gravid amenorrhoea. }}</ref><ref>{{cite journal | vauthors = Romero R, Nicolaides KH, Conde-Agudelo A, O'Brien JM, Cetingoz E, Da Fonseca E, Creasy GW, Hassan SS | display-authors = 6 | title = Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study | journal = Ultrasound in Obstetrics & Gynecology | volume = 48 | issue = 3 | pages = 308–317 | date = September 2016 | pmid = 27444208 | pmc = 5053235 | doi = 10.1002/uog.15953 }}</ref> It has also sometimes been used [[off-label]] as an [[abortifacient]].<ref name="pmid19232600" /><ref name="pmid17634106" /><ref name="pmid29104024">{{cite journal | vauthors = Baxerres C, Boko I, Konkobo A, Ouattara F, Guillaume A | title = Abortion in two francophone African countries: a study of whether women have begun to use misoprostol in Benin and Burkina Faso | journal = Contraception | volume = 97 | issue = 2 | pages = 130–136 | date = February 2018 | pmid = 29104024 | doi = 10.1016/j.contraception.2017.10.011 | quote = It is not hard to find [abortion] services in Cotonou [Benin]. [...] The most commonly used method was [manual vacuum aspiration], followed by curettage, and more rarely a Synergon® (progesterone + estrone) injection, a product indicated in the symptomatic treatment of non-gravid amenorrhea.8 | doi-access = free }}</ref> The medication comes in a three-[[ampoule]] pack, contains 1&nbsp;mg estrone and 10&nbsp;mg progesterone per [[ampoule]], and is administered by [[intramuscular injection]].<ref name="Synergon-Leaflet" /><ref name="pmid19232600" /><ref name="pmid17634106" /><ref name="McDonnell1986">{{cite book| vauthors = McDonnell K |title=Adverse Effects: Women and the Pharmaceutical Industry|url=https://books.google.com/books?id=SgA-AAAAYAAJ|year=1986|publisher=International Organization of Consumers Unions, Regional Office for Asia and the Pacific|isbn=978-967-9973-17-4|page=15|quote=Synergon. 10 mg progesterone. 1 mg folliculine [estrone].}}</ref> The usual dose of the medication is three injections, each two days apart, with the treatment duration not exceeding one week.<ref name="Synergon-Leaflet" /> E1/P4 is or has been available in [[France]], [[Monaco]], and [[Turkey]], as well as in some [[francophone|French-speaking]] [[Africa]]n countries such as [[Benin]] and [[Cameroon]].<ref name="Drugs.com-E2" /><ref name="Drugs.com-P4" /><ref name="Martindale2009" /><ref name="Micromedex">{{cite web | url = https://www.ndrugs.com/?s=synergon#doctor_indications | title = Synergon Indications | work = Generic Drugs | publisher = ndrugs.com }}</ref><ref name="pmid17634106" /><ref name="pmid29104024" /> The medication has been marketed since at least 1952.<ref name="Endokrinologie1952">{{cite book|title=Endokrinologie|url=https://books.google.com/books?id=5dUgAQAAMAAJ|year=1952|publisher=Johann Ambrosius Barth Verlag.|quote=Synergon. Progesterone + Follikulin [Estrone]. Amp. Lab. Hépat.}}</ref>

This combination medication is currently not available in the United States, where progesterone either alone or in combination with estrogen is used to improve menopausal symptoms. Transdermal progesterone (skin patch) and oral micronized progesterone (which is chemically identical to the progesterone produced in women's bodies) have each been shown to be effective treatments for certain symptoms of menopause such as hot flashes and night sweats, otherwise known as vasomotor symptoms or VMS.<ref>{{Cite journal |last=Dolitsky |first=Shelley N. |last2=Cordeiro Mitchell |first2=Christina N. |last3=Stadler |first3=Sarah Sheehan |last4=Segars |first4=James H. |date=2021 |title=Efficacy of progestin-only treatment for the management of menopausal symptoms: a systematic review |url=https://journals.lww.com/10.1097/GME.0000000000001676 |journal=Menopause |language=en |volume=28 |issue=2 |pages=217–224 |doi=10.1097/GME.0000000000001676 |issn=1530-0374}}</ref> Additionally, micronized progesterone cream and micronized progesterone in combined menopausal hormone therapy are both beneficial in preventing skin aging in post-menopausal women. However, there have not been any studies done yet on the effects of micronized progesterone on hair loss due to menopause.<ref>{{Cite journal |last=Gasser |first=S. |last2=Heidemeyer |first2=K. |last3=von Wolff |first3=M. |last4=Stute |first4=P. |date=2021 |title=Impact of progesterone on skin and hair in menopause – a comprehensive review |url=https://www.tandfonline.com/doi/full/10.1080/13697137.2020.1838476 |journal=Climacteric |language=en |volume=24 |issue=3 |pages=229–235 |doi=10.1080/13697137.2020.1838476 |issn=1369-7137}}</ref>

Despite suggestions for using hormone therapy to prevent loss of muscle mass in post-menopausal women (women who are 50 years or older), menopausal hormone therapy involving either estrogen alone or estrogen and progesterone has not been found to preserve muscle mass.<ref>{{Cite journal |last=Javed |first=Ayesha A. |last2=Mayhew |first2=Alexandra J. |last3=Shea |first3=Alison K. |last4=Raina |first4=Parminder |date=2019 |title=Association Between Hormone Therapy and Muscle Mass in Postmenopausal Women: A Systematic Review and Meta-analysis |url=https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2749051 |journal=JAMA Network Open |language=en |volume=2 |issue=8 |pages=e1910154 |doi=10.1001/jamanetworkopen.2019.10154 |issn=2574-3805 |pmc=6716293 |pmid=31461147}}</ref> Menopausal hormone therapy also does not result in body weight reduction, BMI reduction, or change in glucose metabolism.<ref>{{Cite journal |last=Coquoz |first=A. |last2=Gruetter |first2=C. |last3=Stute |first3=P. |date=2019 |title=Impact of micronized progesterone on body weight, body mass index, and glucose metabolism: a systematic review |url=https://www.tandfonline.com/doi/full/10.1080/13697137.2018.1514003 |journal=Climacteric |language=en |volume=22 |issue=2 |pages=148–161 |doi=10.1080/13697137.2018.1514003 |issn=1369-7137}}</ref>


== Estrone ==
== Estrone ==

Revision as of 22:11, 1 August 2023

Estrone/progesterone
Estrone (top) and
progesterone (bottom)
Combination of
EstroneEstrogen
ProgesteroneProgestogen
Clinical data
Trade namesSynergon[1][2]
Other namesE1/P4
Routes of
administration		Intramuscular injection

Estrone/progesterone (E1/P4), sold under the brand name Synergon, is a combination medication formulation of estrone, an estrogen, and progesterone, a progestogen. E1/P4 is used as an injectable preparation to induce withdrawal bleeding in women with non-pregnancy-related amenorrhea (absence of menstruation).[3][1][2][4] [5][6][7] It has also sometimes been used off-label as an abortifacient.[5][6][8] The medication comes in a three-ampoule pack, contains 1 mg estrone and 10 mg progesterone per ampoule, and is administered by intramuscular injection.[3][5][6][9] The usual dose of the medication is three injections, each two days apart, with the treatment duration not exceeding one week.[3] E1/P4 is or has been available in France, Monaco, and Turkey, as well as in some French-speaking African countries such as Benin and Cameroon.[1][2][4][10][6][8] The medication has been marketed since at least 1952.[11]

Estrone

Side effects

Some common side effects seen with the usage of estrogens include: breast swelling, breast tenderness, vaginal itching, abnormal uterine bleeding, weight gain, hair loss, jaundice, and anaphylaxis.[12]

Adverse effect

Some adverse effects seen with the usage of estrogens include: increased risk of venous thromboembolism (VTE), stroke, breast cancer, hypertension, and vaginitis.[12][13]

Contraindications

The use of estrone has several contraindications, some examples including: hypersensitivity, history of some cancers, stroke, venous thromboembolism (VTE), and those currently pregnant or breastfeeding. Estrogens hold a boxed warning to be used at the lowest effective dose and for the shortest possible treatment period if used alone or with another hormone in the progestogen class[13]

Estrone is contraindicated for those that have or are suspected of having breast cancer. The use of estrogens hold a boxed warning with breast cancer for post-menopausal women as this can increase the risk of developing invasive breast cancer.[14] Those with breast cancer become at a greater risk of hypercalcemia and bone metastases when taking estrogens.[15] Post-menopausal women with breast cancer can be seen to develop frailty syndrome when there are changes in blood hormonal levels, including an increased level of estrone. Estrone, the major type of estrogen produced in post-menopausal women, was seen in greater concentrations from standard levels in those that were categorized as prefrail and in those that classified as frail.[16]

The risk of VTE is increased in those that use estrogens, those that currently have or have a history with VTE are at a greater risk of reoccurring VTE with the usage of estrogens.[14][17] The use of estrogens within three weeks postpartum may increase the risk of developing a VTE.[18] Risk of developing initial VTE is also increased with familial history, genetic mutations: factor V Leiden and prothrombin-G20210A, and pregnancy-postpartum with the use of estrogens.[19]

The use of estrogens may affect the ability to breastfeed and can change the composition of breastmilk. Estrogens have been used to suppress lactation which can result in a reduced total duration of lactation and reduced volume or inability to produce breastmilk. Composition of breastmilk produced was also seen to be different resulting in a reduced concentration of proteins in the milk. Babies of mothers that were taking estrogens while breastfeeding were seen to experience slower weight gain. [18]

See also

References

  1. ^ a b c "Estrone". Drugs.com. Archived from the original on 2018-06-21. Retrieved 2019-04-12.
  2. ^ a b c "Progesterone". Drugs.com. Retrieved 2019-04-12.
  3. ^ a b c "Synergon label" (PDF).
  4. ^ a b Sweetman SC, ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. pp. 2101, 2127. ISBN 978-0-85369-840-1. Estrone [...] Progesterone [...] Multi-ingredient: [...] Fr.: Synergon [...] Turk.: Synergon
  5. ^ a b c Addo VN, Tagoe-Darko ED (June 2009). "Knowledge, practices, and attitudes regarding emergency contraception among students at a university in Ghana". International Journal of Gynaecology and Obstetrics. 105 (3): 206–209. doi:10.1016/j.ijgo.2009.01.008. PMID 19232600. S2CID 22216977. Synergon, a combination of progesterone and oestrone in an injectable form, is marketed to induce withdrawal bleeding in women with nongravid amenorrhea; however, it can be used as an arbortifacient [11].
  6. ^ a b c d Kongnyuy EJ, Ngassa P, Fomulu N, Wiysonge CS, Kouam L, Doh AS (July 2007). "A survey of knowledge, attitudes and practice of emergency contraception among university students in Cameroon". BMC Emergency Medicine. 7: 7. doi:10.1186/1471-227X-7-7. PMC 1933435. PMID 17634106. Synergon is dedicated product made up of a combination of progesterone and oestrone in an injectable form. It is used to induce withdrawal bleeding in cases of non-gravid amenorrhoea. In Cameroon, synergon is widely used among students as an abortifacient and is usually administered clandestinely by nurses when a woman presents with amenorrhoea. Such an attitude stemmed from the fact that this product induces withdrawal bleeding, so that some cases of amenorrhoea falsely believed to be due pregnancy are resolved by one or a few intramuscular injections of Synergon. We are not aware of similar findings reported from other countries. Synergon is not produced by the manufacturer as an abortifacient; how it came to be associated with abortion in Cameroon is not known. It is also not known whether it actually induces abortion or it only induces withdrawal bleeding in women with non-gravid amenorrhoea.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  7. ^ Romero R, Nicolaides KH, Conde-Agudelo A, O'Brien JM, Cetingoz E, Da Fonseca E, et al. (September 2016). "Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study". Ultrasound in Obstetrics & Gynecology. 48 (3): 308–317. doi:10.1002/uog.15953. PMC 5053235. PMID 27444208.
  8. ^ a b Baxerres C, Boko I, Konkobo A, Ouattara F, Guillaume A (February 2018). "Abortion in two francophone African countries: a study of whether women have begun to use misoprostol in Benin and Burkina Faso". Contraception. 97 (2): 130–136. doi:10.1016/j.contraception.2017.10.011. PMID 29104024. It is not hard to find [abortion] services in Cotonou [Benin]. [...] The most commonly used method was [manual vacuum aspiration], followed by curettage, and more rarely a Synergon® (progesterone + estrone) injection, a product indicated in the symptomatic treatment of non-gravid amenorrhea.8
  9. ^ McDonnell K (1986). Adverse Effects: Women and the Pharmaceutical Industry. International Organization of Consumers Unions, Regional Office for Asia and the Pacific. p. 15. ISBN 978-967-9973-17-4. Synergon. 10 mg progesterone. 1 mg folliculine [estrone].
  10. ^ "Synergon Indications". Generic Drugs. ndrugs.com.
  11. ^ Endokrinologie. Johann Ambrosius Barth Verlag. 1952. Synergon. Progesterone + Follikulin [Estrone]. Amp. Lab. Hépat.
  12. ^ a b Delgado, Benjamin J.; Lopez-Ojeda, Wilfredo (2023), "Estrogen", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30855848, retrieved 2023-07-31
  13. ^ a b Cusi, Kenneth; Isaacs, Scott; Barb, Diana; Basu, Rita; Caprio, Sonia; Garvey, W. Timothy; Kashyap, Sangeeta; Mechanick, Jeffrey I.; Mouzaki, Marialena; Nadolsky, Karl; Rinella, Mary E.; Vos, Miriam B.; Younossi, Zobair (May 2022). "American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings". Endocrine Practice. 28 (5): 528–562. doi:10.1016/j.eprac.2022.03.010. ISSN 1530-891X.
  14. ^ a b Crandall, Carolyn J.; Hovey, Kathleen M.; Andrews, Christopher A.; Chlebowski, Rowan T.; Stefanick, Marcia L.; Lane, Dorothy S.; Shifren, Jan; Chen, Chu; Kaunitz, Andrew M.; Cauley, Jane A.; Manson, JoAnn E. (January 2018). "Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the Women's Health Initiative Observational Study". Menopause. 25 (1): 11–20. doi:10.1097/GME.0000000000000956. ISSN 1072-3714. PMC 5734988. PMID 28816933.
  15. ^ "The 2017 hormone therapy position statement of The North American Menopause Society". Menopause. 24 (7): 728–753. July 2017. doi:10.1097/GME.0000000000000921. ISSN 1072-3714.
  16. ^ García-Sánchez, Javier; Mafla-España, Mayra Alejandra; Tejedor-Cabrera, Carlos; Avellán-Castillo, Olga; Torregrosa, María Dolores; Cauli, Omar (2022-03-07). "Plasma Aromatase Activity Index, Gonadotropins and Estrone Are Associated with Frailty Syndrome in Post-Menopausal Women with Breast Cancer". Current Oncology. 29 (3): 1744–1760. doi:10.3390/curroncol29030144. ISSN 1718-7729. PMC 8947022. PMID 35323344.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  17. ^ "Different kinds of oral contraceptive pills in polycystic ovary syndrome: a systematic review and meta-analysis". academic.oup.com. Retrieved 2023-07-31.
  18. ^ a b "Contraceptives, Oral, Combined", Drugs and Lactation Database (LactMed®), Bethesda (MD): National Institute of Child Health and Human Development, 2006, PMID 30000354, retrieved 2023-07-31
  19. ^ van Vlijmen, Elizabeth F. W.; Veeger, Nic J. G. M.; Middeldorp, Saskia; Hamulyák, Karly; Prins, Martin H.; Büller, Harry R.; Meijer, Karina (2011-08-25). "Thrombotic risk during oral contraceptive use and pregnancy in women with factor V Leiden or prothrombin mutation: a rational approach to contraception". Blood. 118 (8): 2055–2061. doi:10.1182/blood-2011-03-345678. ISSN 0006-4971.
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