Long-term effects of cyclic combined conjugated estrogens and dydrogesterone in post-menopausal women
Barry G. Wren in Progress in the Management of the Menopause, 2020
Hormonal replacement therapy is currently used for the control of climacteric symptoms, and for the prevention of long-term consequences of menopause. Chronic hypoestrogenism in post-menopausal years causes a critical decrease in bone mineral density (BMD) that is an important determinant of fracture risk1-5. Estrogen replacement therapy prevents the lowering of BMD related to peri-and post-menopausal hypoestrogenism4-7. In addition, post-menopausal estrogen supplementation can exert cardioprotective effects with substantial reduction of morbidity and mortality for cardiovascular disease8-16. During estrogen therapy, progestin supplementation is mandatory to prevent endometrial hyperstimulation17-23 . However, the administration of progestogens can jeopardize the beneficial effects of estrogens on cardiovascular protection24, 25. The metabolic effects depend on the type and dose of progestogens. Dydrogesterone (DD) is a potent orally active progestogen, similar to endogenous progesterone in its molecular structure and biological actions, and devoid of any androgenic, anabolic or estrogenic effect26-31. Sequential DD administration was reported to antagonize the estrogenic effect on endometrial profferation26-31. In the present paper we report clinical and metabolic effects of the long-term administration of DD in combination with conjugated estrogens (CE) in early post-menopausal women.
Debate: Should Progestogens Be Used in Recurrent Pregnancy Loss? Yes
Howard J.A. Carp in Recurrent Pregnancy Loss, 2020
In addition to micronized progesterone, a stereoisomer of progesterone dydrogesterone has been widely studied in various clinical trials. Dydrogesterone has 5–6 times higher bioavailability than progesterone itself and higher receptor binding selectivity [8]. These result in a significantly lower oral therapeutic dose, which is approximately 10–20 times less than micronized progesterone. El-Zibdeh [9] conducted a three-arm study on 180 women that compared dydrogesterone treatment with human chorionic gonadotropin (hCG), both in combination with standard supportive care and with standard supportive care alone. Women recruited for the study were less than 35 years old with history of ³3 unexplained recurrent consecutive miscarriages. All women received standard supportive care, including multivitamin supplements and recommended bed rest, and were followed routinely in the antenatal clinic. Eighty-two women received dydrogesterone 10 mg twice daily with standard supportive care from diagnosis of pregnancy until 12 weeks, 50 women received hCG 5000 IU intramuscularly every 4 days with standard supportive care from diagnosis of pregnancy until 12 weeks, and in the third arm 48 women (controls) received standard supportive care alone. Miscarriage was significantly (p ≤ 0.05) more common in the control group (29%; 14/48 women) than in the dydrogesterone group (13.4%; 11/82 women). There were no significant differences between the hCG group (18%; 9/50 women) and the control group [9].
Management
John C Stevenson, Michael S Marsh in An Atlas of Osteoporosis, 2007
Whilst a dose-dependent effect of estrogen has been shown in several studies, it has also been found that older postmenopausal women may not need as much estrogen as younger women to achieve the same skeletal effect. Lees and Stevenson9 conducted a double-blind, randomized, placebocontrolled study of the effects of two different doses (1 mg and 2 mg) of oral estradiol with the cyclical addition of various doses of dydrogesterone. Spinal and hip bone density was measured by dual-energy X-ray absorptiometry (DEXA) for 2 years. The bone density rose in all treated groups, with a somewhat greater increase with the higher dose, and fell in the placebo group. The increase in spine bone density for the 1-mg estradiol group in the oldest quartile of women was similar to that seen with 2 mg estradiol in the youngest quartile of women (Figure 6.1).
Dydrogesterone indications beyond menopausal hormone therapy: an evidence review and woman’s journey
Published in Gynecological Endocrinology, 2021
During their reproductive years many women suffer from various hormone-related medical conditions. If hormonal treatment is indicated, an increasing number of women prefer to receive bio-identical rather than synthetic hormones. However, bio-identical micronized progesterone is not always well tolerated due to its central nervous system effects. As a stereoisomer of progesterone, dydrogesterone does not display such effects and may be used as an optimal alternative. As the case study illustrates, dydrogesterone has multiple potential clinical uses throughout a woman’s reproductive years, from adolescence through to peri- and post-menopause. Apart from its indication as a component of menopausal hormone therapy, dydrogesterone can be used to treat a range of conditions affecting menses and pregnancy such as dysmenorrhea, irregular menstrual cycles, premenstrual syndrome, threatened or recurrent miscarriage, and luteal phase support during assisted reproduction. Evidence of benefit with dydrogesterone is particularly strong for the prevention of threatened or recurrent miscarriage.
Steroid hormones and pregnancy
Published in Gynecological Endocrinology, 2019
Nancy Noyola-Martínez, Ali Halhali, David Barrera
Regarding the prevention of miscarriages, the results of a randomized, double-blind, placebo-controlled and international multicenter study have demonstrated that vaginal micronized P4 administration in early pregnancy did not result in significant decrease in unexplained recurrent miscarriages as compared with placebo [79]. Using progestogen treatment, the results obtained are conflictive. Indeed, it has been postulated in a double-blind and randomized controlled trial that treatment with dydrogesterone in the first trimester of pregnancy will significantly reduce the risk of miscarriage in women with threatened miscarriage [80]. In addition, the results of systemic reviews have shown that pregnant women treated with progestogen have a significant reduction in the risk of miscarriage [81–83]. However, these positive effects of progestogen have not been observed in other studies. Indeed, progestogen treatment has been evaluated in a meta-analysis of 14 trials including 2158 women and the authors of this review concluded that regardless of gravity and number of previous miscarriages, progestogen treatment, independently of route of administration (oral, intramuscular, vaginal), did not reduce significantly the risk of miscarriage as compared with placebo or no treatment [84]. Thus, for the prevention of miscarriage, the use of P4 seems to be definitely discarded and dydrogesterone treatment deserves to be further investigated.
Vasomotor tone-associated factors and pregnancy outcomes of women who undergo in vitro fertilization
Published in Growth Factors, 2021
Yonglian Lan, Xiaokui Yang, Yu Liang, Lingling Lei, Ying Li, Shuyu Wang
A standard mid-luteal long protocol was used to induce ovulation. Before menstruation, triptorelin acetate (Ferring GmbH, Germany) was subcutaneously injected at a dose of 0.1 mg/day for 7 days. When the ovarian function was inhibited (E2 level, <50 pg/ml; follicle diameter in both ovaries, <5 mm; endometrial thickness, <5 mm), recombinant human follicle-stimulating hormone (Merck Serono, Switzerland) was injected at a dose of 150–225 IU/day to induce ovulation. The ovarian follicle was monitored until suitable ovarian follicles (one dominant follicle ≥18 mm or three dominant follicles ≥17 mm) were observed. After injection of 250 µg of recombinant human chorionic gonadotropin (Merck Serono) for 36 h, the oocytes were collected and immediately fertilized. At 72 h post-fertilization, two embryos at the cleavage stage were implanted. Starting from the day of oocyte retrieval, oral dydrogesterone at a dose of 10 mg twice a day and vaginal utrogestan at a dose of 0.2 g thrice a day were administered for luteal support.
Related Knowledge Centers
- Dysmenorrhea
- Infertility
- Luteal Phase
- Miscarriage
- Progestogen
- Drug
- Recurrent Miscarriage
- Pregnancy
- Abnormal Uterine Bleeding
- Endometriosis