Estudos
http://aformulabr.com.br/qrcode/progesteronafv01.pdf
PROGESTERONA
Equilíbrio hormonal feminino DESCRIÇÃO A Progesterona é um hormônio feminino isolado que apresenta-se sob a forma de cristais micronizados. MECANISMO DE AÇÃO Progesterona possui ações neuroendócrinas reduzindo a frequência de GnRH (hormônio liberador de gonadotrofina)
na fase lútea, no trato reprodutor diminui a proliferação do endométrio, induz o desenvolvimento das glândulas
mamárias e possui efeitos metabólicos elevando a insulina basal e os níveis de insulina pós-prandial.
INDICAÇÕES
Contracepção isolada ou com estrogênio;
Terapia de reposição hormonal (menorragia, endometriose, etc.);
Amenorreia secundária;
Hemorragia uterina anormal;
Infertilidade;
Contrações uterinas ;Parto prematuro.
DOSE USUAL
Recomendação oral de 100 a 600mg de Progesterona ao dia.
Recomendação tópica de 5 a 100mg ou até 20% de Progesterona ao dia.
SUGESTÕES DE FÓRMULAS
PRINCIPAIS REFERÊNCIAS BATISTUZZO, J. A O; ITAYA, M.; ETO, Y. Formulário Médico-Farmacêutico. 5 ed. São Paulo: Pharmabooks, 2015.
STUTE P.; NEULEN, J.; WILDT, L. The impact of micronized progesterone on the endometrium: a systematic review. Climacteric. p. 1-13. 2016.
Disponível em:<http://www.ncbi.nlm.nih.gov/pubmed/27277331>. Acesso em: 01 de Julho de 2016.
Progesterona.................................... 100 - 600mg
Modo de uso: 01 dose, 1 vez ao dia, pela manhã.
Indicação: amenorreia secundária, endometriose,
sangramento uterino disfuncional, reposição
hormonal e síndrome pré-menstrual.
Progesterona...................................................100mg
Óvulo qsp.................................................... 1 unidade
Modo de uso: 1 unidade ao dia.
Indicação: declínio androgênico, manutenção da
gravidez e infertilidade.
PROGESTERONA
ESTUDOS CLÍNICOS
The impact of micronized progesterone on the endometrium: a systematic review.
Postmenopausal women with an intact uterus using estrogen therapy should receive a progestogen for endometrial
protection. International guidelines on menopausal hormone therapy (MHT) do not specify on progestogen type, dosage,
route of application and duration of safe use. At the same time, the debate on bioidentical hormones including micronized
progesterone increases. Based on a systematic literature review on micronized progesterone for endometrial protection,
an international expert panel's recommendations on MHT containing micronized progesterone are as follows: (1) oral
micronized progesterone provides endometrial protection if applied sequentially for 12-14 days/month at 200 mg/day for
up to 5 years; (2) vaginal micronized progesterone may provide endometrial protection if applied sequentially for at least
10 days/month at 4% (45 mg/day) or every other day at 100 mg/day for up to 3-5 years (off-label use); (3) transdermal
micronized progesterone does not provide endometrial protection.
The impact of progesterone supplementation on pregnancy rates after intrauterine insemination in patients
developing a single follicle.
The objective was to determine whether progesterone support affects pregnancy rates in patients who develop a single
follicle. This was a non-randomized prospective controlled study performed on 591 intrauterine insemination (IUI) cycles
that developed a single follicle; 337 women received 100 mg oral progesterone daily. The pregnancy rate was 24.3%,
or 82 out of 337, in the group receiving progesterone support compared with 14.96%, or 254 out of 591, in the group
with no progesterone support. IUI luteal phase supplementation with oral progesterone may improve clinical pregnancy
rates when begun the day after insemination.
Assessment of sub-endometrial blood flow parameters following dydrogesterone and micronized vaginal
progesterone administration in women with idiopathic recurrent miscarriage: a pilot study.
AIM: To evaluate differences in uteroplacental blood flow and pregnancy outcome in women with idiopathic recurrent
spontaneous miscarriage (IRSM) following administration of micronized vaginal progesterone and oral dydrogesterone.
METHODS: One hundred and thirty-three women (aged 23-40 years) who had had early miscarriages and spontaneous
conception participated. Oral dydrogesterone (group A, n = 51) and micronized vaginal progesterone (group B, n = 50)
were administrated for luteal support and compared. Pregnant women without history of recurrent miscarriage served
as controls (group C, n = 32). The outcome measures consisted of endometrial blood flow parameters by Doppler indices
and ongoing pregnancy rate. RESULTS: Before progesterone supplementation, resistivity index (RI) and pulsatility index
(PI) were found to be significantly higher in groups A and B as compared to controls. Although statistically not significant,
end diastolic velocity (EDV) and systolic/diastolic (S/D) ratio was found to be superior in controls than IRSM women.
Peak systolic velocity (PSV) was comparable between IRSM and non-IRSM groups. Following progesterone
supplementation, groups A and B showed a highly significant reduction in RI, PI and an increase in EDV. A relative
increase in the value of PSV was observed in group A as compared to group B. There was remarkable difference in S/D
in both groups. Although not statistically significant, group C showed reduction in RI, PI, PSV, EDV and S/D ratio.
Pregnancy salvage rates were higher in group A (92.0%) as compared to group B (82.3%).
CONCLUSION: Progesterone supplementation appears to lower vascular resistance in women with IRSM. Oral
dydrogesterone appears to be equally effective in improving endometrial blood flow as compared with micronized
progesterone.
Vaginal progesterone on the prevention of preterm birth and neonatal complications in high risk women: A
randomized placebo-controlled double-blind study.
BACKGROUND: Preterm birth is the major cause of neonatal mortality and morbidity. OBJECTIVE: The aim of this
study was to evaluate the effect of prophylactic vaginal progesterone on decreasing preterm birth rate and neonatal
complications in a high-risk population. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled
study was performed on 100 high-risk singleton pregnancies.
Vaginal suppository progesterone (400 mg) or placebo was administered daily between 16-22 wks to 36 wks of
gestation. Progesterone (n=50) and placebo (n=50) groups were compared for incidence of preterm delivery and
neonatal complications. RESULTS: The preterm birth rate was 52%. Preterm birth rate before the 37 wks of gestation
(68% vs. 36%: RR=1.89, 95% CI: 1.25-2.86) and also before the 34 wks of gestation (42% vs. 18%: RR=2.33, 95% CI:
1.19-4.58) in placebo group was significantly higher than progesterone group. Our study also showed that the
administration of vaginal progesterone was associated with a significant reduction in the risk of birth weight ≤2500 gr,
the rates of respiratory distress syndrome (RDS) and admission to the Neonatal Intensive Care Unit (NICU) in the
progesterone group when compared with the placebo group. However, there was no significant difference between the
two groups in terms of neonatal death, days of admission in NICU, intraventricular hemorrhage and necrotizing
enterocolitis. CONCLUSION: Prophylactic vaginal progesterone reduced the rate of preterm delivery, the risk of a birth
weight ≤2500 gr, the rates of RDS and admission to NICU in women who were at risk of preterm delivery.
Prolonged progesterone administration is associated with less frequent cervicovaginal colonization by
Ureaplasma urealyticum during pregnancy - Results of a pilot study.
BACKGROUND: Preterm birth is a leading cause of perinatal mortality and morbidity. Heavy cervicovaginal Ureaplasma
colonization is thought to play a role in the pathogenesis of preterm birth. The administration of vaginal progesterone
has been shown to reduce the incidence of preterm birth in women with short cervical length. Steroid hormones seem
to modulate the presence of microorganisms in the vagina. The aim of this study was to assess whether the treatment
with vaginal progesterone could reduce the incidence of preterm birth and cervicovaginal colonization by Ureaplasma
urealyticum in a cohort of pregnant women with threatened preterm labor. METHODS: A cohort of 63 females who
presented with regular contractions and/or short cervical length between 24-32 weeks of gestation were recruited into
a prospective study. 70% of patients had been treated with vaginal progesterone prior to recruitment and these patients
continued with the treatment until birth. All patients were tested for the presence of cervicovaginal Ureaplasma
urealyticum colonization at admission. The primary endpoint was preterm birth before 37 weeks. RESULTS: The
incidence of preterm delivery was significantly increased in patients who tested positive for Ureaplasma urealyticum.
Prolonged vaginal progesterone administration was associated with less frequent cervicovaginal colonization by U.
urealyticum. Cervicovaginal colonization by U. urealyticum and absence of progesterone treatment were identified as
two independent risk factors for preterm delivery. CONCLUSIONS: Our results demonstrate the beneficial effects of
progesterone administration in reducing the incidence of cervicovaginal colonization by Ureaplasma urealyticum.
A randomized controlled trial of intramuscular versus vaginal progesterone for the prevention of recurrent
preterm birth.
OBJECTIVE: To compare the efficacy of intramuscular hydroxyprogesterone caproate with that of vaginal progesterone
for prevention of recurrent preterm birth. METHODS: A prospective randomized controlled trial was conducted at a US
tertiary care center between June 1, 2007, and April 30, 2010.Women with singleton pregnancies (16-20 weeks) and a
history of spontaneous preterm birth were randomly allocated using a computer-generated randomization sequence to
receive either a weekly intramuscular injection of hydroxyprogesterone caproate (250 mg) or a daily vaginal
progesterone suppository (100 mg). Participants, investigators, and assessors were not masked to group assignment.
The primary outcome was birth before 37 weeks of pregnancy. Per-protocol analyses were performed: participants who
completed follow-up were included. RESULTS: Analyses included 66 women given intramuscular progesterone and 79
given vaginal progesterone. Delivery before 37 weeks was recorded among 29 (43.9%) women in the intramuscular
progesterone group and 30 (37.9%) in the vaginal progesterone group (P=0.50). CONCLUSION: Weekly intramuscular
administration of hydroxyprogesterone caproate and daily vaginal administration of a progesterone suppository
exhibited similar efficacy in reducing the rate of recurrent preterm birth
The effect of luteal-phase support with vaginal progesterone on pregnancy rates in gonadotropin and
clomiphene citrate/intra-uterine insemination cycles in unexplained infertility: A prospective randomised study.
The purpose of this study is to analyse the effect of luteal-phase support on pregnancy rates in gonadotropin + intra-
uterine insemination (Gn/IUI) and clomiphene citrate (CC) +IUI (CC/IUI) cycles in patients with unexplained infertility.
Equal numbers of patients were recruited in two treatment arms (CC/IUI and Gn/IUI) (n = 100, n = 100, respectively). In
each group, 50 patients received vaginal progesterone for 14 days (Crinone 8% vaginal gel, 90 mg per day) for luteal-
phase support from the day after IUI and continued until menstruation or the 10th week of gestation if pregnant. There
were 29 clinical pregnancies among 200 patients. Pregnancy rates were 12% in CC/IUI cycles, 10% in luteal-phase-
supported CC/IUI cycles 16% in Gn/IUI cycles and 20% in luteal-phase-supported Gn/IUI cycles. Although pregnancy
rates were higher in Gn/IUI cycles compared to CC/IUI cycles, luteal-phase support did not significantly affect the
pregnancy rates in both groups. This study implies that luteal-phase support with progesterone has no pronounced
beneficial effect on pregnancy rates in either CC/IUI or Gn/IUI cycles in patients with unexplained infertility.
Progesterone or progestin as menopausal ovarian hormone therapy: recent physiology-based clinical
evidence.
PURPOSE OF REVIEW: Provide evidence-based recent data on oral micronized progesterone (OMP) and progestins
in menopausal hormonal therapy (MHT). RECENT FINDINGS: Medroxyprogesterone acetate (MPA) increases breast
cancer acting through the glucocorticoid receptor; progestins in MHT increase thrombosis more than oral estrogens;
MPA, but not OMP or other progestins, increase monocyte cell endothelium adhesion; MPA and estradiol (E2)/MPA
have negative brain effects, whereas E2/progesterone (P4) has neuroregenerative brain effects. The 'window of
opportunity' cardiovascular disease hypothesis is not supported by a randomized controlled trial showing that
transdermal estradiol with sequential OMP in early menopause does not prevent increased carotid intimal media
thickness; P4 in the cardiac electrical system opposes E2 effects and prevents sudden death/long QT syndrome;
transdermal estradiol/OMP does not increase venous thromboembolism in observational data. P4 decreases breast cell
proliferation and improves prognosis through P4 receptor alteration of estrogen receptor α genetic effects; OMP with
conjugated equine estrogen (CEE)/estrogen (E)/E2 does not increase breast cancer in two prospective cohorts, one
population-based. Endometrial cancer is increased in MHT of CEE/E/E2+cyclic OMP at 200 mg/day. SUMMARY: New
data show CEE/E/E2+MPA/P mechanisms for negative breast cancer, venous thromboembolism, cardiovascular
system, and brain effects. OMP/P4 counterbalances CEE/E/E2-related negative effects on breast cancer and long QT
syndrome. OMP effectively treats vasomotor symptoms and sleep disturbances, and could safely be used alone for
symptomatic menopause.
Luteal phase support in intrauterine insemination cycles: a prospective randomized study of 300 mg versus
600 mg intravaginal progesterone tablet.
Vaginal progesterone (P) has been suggested to be used for luteal phase support (LPS) in controlled ovarian stimulation
(COH)-intrauterine insemination (IUI) cycles, however, no concensus exists about the best P dose. Therefore,
considering the fecundability rate as the primary end point, our main objective was to find the optimal dose of P in COH-
IUI cycles, comparing the two groups of women, each of which comprised of 100 women either on 300 mg or 600 mg of
intravaginal P tablets, in a prospective randomized study design. The mean age of the women, duration of infertility,
basal and day of hCG injection hormone levels in the female and sperm parameters were similar in the two study groups.
Also, duration and dose of gonadotropin given, number of follicles, endometrial thickness, the total, ongoing and multiple
pregnancy rates were comparable in both groups. We, therefore, claim that 300 mg of intravaginal micronized P should
be the maximum dose of LPS in IUI cycles.
Hormone therapy and risk of venous thromboembolism among postmenopausal women.
Despite a decrease in the use of postmenopausal hormone therapy (HT) over the last decade, many women are still
prescribed this treatment, as it remains the most effective means of counteracting climacteric symptoms. Its use declined
when it was shown that HT increases the risk of breast cancer, stroke and venous thromboembolism (VTE).
Nevertheless, that benefit/risk ratio was established among women using oral estrogens alone or combined with a
specific progestogen and it cannot necessarily be extrapolated to other HTs. Oral estrogens increase the risk of VTE
especially during the first year of treatment and past users revert to a similar risk as women who have never used them.
There is now growing evidence that VTE risk among HT users strongly depends on the route of administration. Indeed,
transdermal estrogens, unlike oral estrogens, are not associated with an increased VTE risk and biological data support
this difference between oral and transdermal estrogens. In addition, transdermal estrogens may not confer additional
risk in women at high risk of VTE. Significant differences in thrombotic risk between HT preparations also relate to the
concomitant progestogen. Studies have consistently shown that VTE risk is higher among users of combined estrogens
plus progestogens than among users of estrogens alone. With respect to the different pharmacological classes of
progestogens, two observational studies found that norpregnane derivatives are associated with an increased VTE risk,
whereas micronized progesterone may be safe with respect to thrombotic risk. In conclusion, transdermal estrogens
alone or combined with micronized progesterone may represent the safest alternative for women who require HT.
Vaginal micronized progesterone capsule versus vaginal progesterone gel for lutheal support in
normoresponder IVF/ICSI-ET cycles.
OBJECTIVE: To compare the outcomes of luteal phase support by micronized progesteron vaginal capsule 600mg/day
and progesterone vaginal gel 180mg/day in the normoresponder IVF/ICSI-ET cycles of the patients down-regulated via
GnRH agonist long protocol or fixed antagonist protocol below 40 years of age. METHODS: A total of 463
normoresponder cycles between January 2013 and December 2013 were retrospectively analyzed. Those with a
BMI>28 kg/m(2), any kind of uterine, ovarian or adnexial pathology, any significant systemic, endocrine or metabolic
disease or who were reported as azoospermia, were excluded from the study. The patients were grouped according to
the usage of micronized progesterone vaginal capsule 600mg/day (Group 1) or progesterone vaginal gel 180mg/day
(Group 2) as luteal phase support. Treatment cycle characteristics and pregnancy outcomes were compared between
groups. RESULTS: Group-I included 220 cycles and group 2 included 243 cycles. Although the MII oocyte percentage
among the total number of MII oocytes was significantly higher in Group-II (77.5% and 80.2%; p=0.034), positive ß-hCG
(32.3% and 21.8%; p=0.015) and clinical pregnancy (27.3% and 17.7%; p=0.018) rates were significantly higher in
Group-I. No difference was observed between groups regarding the ongoing pregnancy rates (23.2% and 17.3%;
p=0.143). CONCLUSION: Micronized progesterone vaginal capsule 600mg daily used for luteal support in the IVF/ICSI-
ET cycles was observed to significantly increase the biochemical and clinical pregnancy rates compared to progesterone
vaginal gel 180mg daily. However, no difference was observed between two groups regarding ongoing pregnancy rates.
Progesterone support for frozen embryo transfer: intramuscular versus vaginal suppository demonstrates no
difference in a cohort.
OBJECTIVE: To evaluate pregnancy rates based on the route of progesterone replacement in frozen embryo transfer
(FET) cycles. STUDY DESIGN: A randomized controlled trial and retrospective analysis. In the randomized group 76
FET cycles were randomized. In the retrospective group 508 FET cycles were reviewed. Intramuscular (IM) proges-
erone in oil 100 mg daily or oral micronized progesterone prior to transfer followed by compounded vaginal proges-
erone 200 mg 3 times daily (OV). The main outcome measure was the clinical pregnancy rate (CPR). RESULTS:
Baseline characteristics did not vary be-ween groups in either cohort. In the randomized group there were no significant
differences in CPR (31.43% vs. 21.05%) or live birth rate (LBR) (31.43% vs. 18.92%) for IM and OV progesterone
replacement, respectively. In the retrospective cohort patients there wore also no significant differences in CPR (35.56%
vs. 32.35%) or LBR (32.23% vs. 28.51%)f or the IM and OVp rogester-ne replacement groups, respectively.
CONCLUSION: This study demonstrates that either OV or IM progesterone is effective for luteal phase support for
FETs.
Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a
multicenter, randomized, double-blind, placebo-controlled trial.
Objectives Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This
study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the
risk of preterm birth and associated neonatal complications in women with a sonographic short cervix. Methods This
was a multicenter, randomized, doubleblind, placebo-controlled trial that enrolled asymptomatic women with a singleton
pregnancy and a sonographic short cervix (10–20 mm) at 19 + 0 to 23+ 6 weeks of gestation. Women were allocated
randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks,
rupture of membranes or delivery, whichever occurred first. Randomization sequence was stratified by center and history
of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by
intention to treat.
REFERÊNCIAS
AZARGOON, A.; GHORBANI, R.; ASLEBAHAR, F. Vaginal progesterone on the prevention of preterm birth and neonatal complications in high risk
women: A randomized placebo-controlled double-blind study. Int J Reprod Biomed (Yazd). v. 14, n. 5, p. 309-316. 2016. Disponível
em:<http://www.ncbi.nlm.nih.gov/pubmed/27326415>. Acesso em: 04/07/2016, às 16:33.
BIBEROGLU, E. H. et al. Luteal phase support in intrauterine insemination cycles: a prospective randomized study of 300 mg versus 600 mg
intravaginal progesterone tablet. Curr Opin Gynecol Endocrinol. v. 32, n. 1, p. 55-57. 2016. Disponível
em:<http://www.ncbi.nlm.nih.gov/pubmed/26291817>. Acesso em: 05/07/2016, às 10:37.
CANONICO, M. Hormone therapy and risk of venous thromboembolism among postmenopausal women. Maturitas. v. 82, n. 3, p. 304-307. 2015.
Disponível em:<http://www.ncbi.nlm.nih.gov/pubmed/26276103>. Acesso em: 05/07/2016, às 10:51.
ELIMIAN, A. et al. A randomized controlled trial of intramuscular versus vaginal progesterone for the prevention of recurrent preterm birth. Int J
Gynaecol Obstet. doi: 10.1016/j.ijgo.2016.01.010. 2016. Disponível em:<http://www.ncbi.nlm.nih.gov/pubmed/27168167>. Acesso em:
04/07/2016, às 16:49.
GHOSH, S. et al. Assessment of sub-endometrial blood flow parameters following dydrogesterone and micronized vaginal progesterone
administration in women with idiopathic recurrent miscarriage: a pilot study. J Obstet Gynaecol Res. v. 40, n. 7, p. 1871-1876. 2014. Disponível
em:<http://www.ncbi.nlm.nih.gov/pubmed/25056464>. Acesso em: 01/07/2016, às 10:10.
GÜVEN, D. et al. The impact of progesterone supplementation on pregnancy rates after intrauterine insemination in patients developing a single
follicle. Hum Fertil (Camb). p. 1-3. 2016. Disponível em:<http://www.ncbi.nlm.nih.gov/pubmed/27321474>. Acesso em: 01/07/2016, às 09:49.
KARADAG, B. et al. The effect of luteal-phase support with vaginal progesterone on pregnancy rates in gonadotropin and clomiphene citrate/intra-
uterine insemination cycles in unexplained infertility: A prospective randomised study. J Obstet Gynaecol. DOI: 10.3109/01443615.2016.1154511.
2016. Disponível em:<http://www.ncbi.nlm.nih.gov/pubmed/27146108>. Acesso em: 04/07/2016, às 16:56.
KOUCKÝ, M. et al. Prolonged progesterone administration is associated with less frequent cervicovaginal colonization by Ureaplasma urealyticum
during pregnancy - Results of a pilot study. J Reprod Immunol. doi: 10.1016/j.jri.2016.04.285. 2016. Disponível
em:<http://www.ncbi.nlm.nih.gov/pubmed/27172838>. Acesso em: 04/07/2016, às 16:43.
LEONARD, P. H. et al. Progesterone support for frozen embryo transfer: intramuscular versus vaginal suppository demonstrates no difference in a
cohort. J Reprod Med. v. 60, n. 3-4, p. 103-108. 2015. Disponível em:<http://www.ncbi.nlm.nih.gov/pubmed/25898472>. Acesso em: 05/07/2016,
às 11:25.
PRIOR, J. C. Progesterone or progestin as menopausal ovarian hormone therapy: recent physiology-based clinical evidence. Curr Opin
Endocrinol Diabetes Obes. v. 22, n. 6, p. 495-501. 2015. Disponível em:<http://www.ncbi.nlm.nih.gov/pubmed/26512775>. Acesso em:
05/07/2016, às 10:24.
SOFUOGLU, K. et al. Vaginal micronized progesterone capsule versus vaginal progesterone gel for lutheal support in normoresponder IVF/ICSI-ET
cycles. Pak J Med Sci. v. 31, n. 2, p. 314-319. 2015. Disponível em:<http://www.ncbi.nlm.nih.gov/pubmed/26101482>. Acesso em: 05/07/2016, às
11:05.
STUTE P.; NEULEN, J.; WILDT, L. The impact of micronized progesterone on the endometrium: a systematic review. Climacteric. p. 1-13. 2016.
Disponível em:<http://www.ncbi.nlm.nih.gov/pubmed/27277331>. Acesso em: 01/07/2016, às 09:17.
Hassan, S. S., Romero, R., Vidyadhari, D., Fusey, S., Baxter, J. K., Khandelwal, M., ... & Dayal, A. (2011). Vaginal progesterone reduces the rate of
preterm birth in women with a sonographic short cervix: a multicenter, randomized, double‐blind, placebo‐controlled trial. Ultrasound in Obstetrics &
Gynecology, 38(1), 18-31.Disponivel em < https://obgyn.onlinelibrary.wiley.com/doi/full/10.1002/uog.9017> Acesso em :18 de Abril de 2019.