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.

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