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Endocrine, paracrine and intracrine mechanisms of growth regulation in normal and malignant breast epithelium
Published in A. R. Genazzani, Hormone Replacement Therapy and Cancer, 2020
J. R. Pasqualini, G. S. Chetrite
It was observed that 19-nor-progestins (such as those derived from testosterone: norethindrone, norgestrel or norethynodrel) possess a weak estrogenic activity and can stimulate (at 10–6 mol/l) the proliferation of estrogen receptor-positive but not estrogen receptor-negative breast cancer cells32. Interesting data were obtained with nomegestrol acetate (Lutenyl®), a 19-nor-progestin derivative. This compound does not possess estrogenic activity and is exclusively antiproliferative in MCF-7 and T-47D cells. It was postulated that the estrogenic activity is determined mainly by the 17α-hydroxyl group associated with estrogenic progestins, rather than by the absence of a methyl group at the C19 position38.
Progestogen use and breast cancer
Published in Barry G. Wren, Progress in the Management of the Menopause, 2020
Using human breast-cancer cell lines in culture, Catherino ard co-workers33 described the estrogenic activity of some 19-nortestosterone derivatives such as norgestrel and gestodene, which were shown to stimulate breast-cancer cell growth through an estrogenreceptor mechanism. Later, Catherino and Jordan34 tested 19-norprogesterone derivatives using the same model. They showed that nomegestrol acetate, a 19-norprogesterone derivative, inhibited T47D-cell growth and did not exhibit any estrogenic effect. They found that only estradiol, norgestrel and RU486 stimulate cell proliferation while R5020, MPA and nomegestrol acetate were unable to provide a proliferative stimulus. They also demonstrated that this effect of the former molecules on proliferation was an estrogen receptor-mediated effect.
Combined hormonal contraception
Published in John Guillebaud, Contraception Today, 2019
Acne, seborrhoea and sometimes hirsutism are often be benefited by these, which contain drospirenone (DSP). DSP differs from other progestogens in COCs because: It is an anti-androgen, about one third as strong as CPA, the strongest anti-androgen used in contraception. (Dienogest is similar, and nomegestrol acetate has the same potency or somewhat less).It has diuretic properties from anti-mineralocorticoid activity.
Hormonal and natural contraceptives: a review on efficacy and risks of different methods for an informed choice
Published in Gynecological Endocrinology, 2023
Andrea R. Genazzani, Tiziana Fidecicchi, Domenico Arduini, Andrea Giannini, Tommaso Simoncini
The affinity of progestin for different receptors can be highly different. First, the effect on androgen receptor can vary. If oldest progestins maintain an androgenic activity (i.e. levonorgestrel), others (norgestimate, gestodene, and desogestrel) have a minimal or no androgenic activity, until those that have an anti-androgenic activity (dienogest, cyproterone acetate, drospirenone, nomegestrol acetate and chlormadinone acetate). The antiandrogenic effect on androgen receptors is maximum with cyproterone acetate; dienogest and drospirenone are approximately 40% and 30% of its potency [31, 32]. Progestins with androgenic effect can also modulate and counteract both the positive and negative metabolic effects of the estrogenic component. This capacity is lost from no- or anti-androgenic progestins: this means that both the positive effect of estrogens on carbohydrate and lipid metabolism, and their stimulatory effects on coagulation factors are at their maximal expression with these progestins [33]. Progestins for HC should be carefully chosen according to the aim of the treatment for each patient.
NOMAC-E2 shows a better contraceptive effectiveness than LNG combined oral contraceptives in women under 25: real-world PRO-E2 study
Published in Gynecological Endocrinology, 2023
Sophia von Stockum, Anja Bauerfeind, Kerstin Becker, Christian Franke, Franca Fruzzetti, Joaquim Calaf, Christoph Keck, Klaas Heinemann
NOMAC-E2 is a monophasic COC containing a fixed dose of the progestin nomegestrol acetate (NOMAC, 2.5 mg) and the synthetic analogue of the endogenous estrogen 17β-estradiol (E2, 1.5 mg), which is taken in a 24/4 day regimen with 4 days of placebo. At dosages of 1.5 mg/day or more, NOMAC effectively suppresses gonadotropic activity and ovulation in women of reproductive age [24]. Results from the PRO-E2 study, a large, prospective, observational study designed to compare the risks of NOMAC-E2 versus levonorgestrel-containing COCs (COCLNG) in a real-world setting, have shown that NOMAC-E2 use was not associated with a higher risk of thromboembolic events (primary outcome of the study) [25] and showed a statistically significant better effectiveness [26] compared with COCLNG. We performed a sub-population analysis limited to participants under 25 years to specifically investigate contraceptive effectiveness and effects on acne, weight, and mood in young users. This age threshold was based on the World Health Organization (WHO) definition for ‘young people’ [18].
Pharmacodynamics of combined estrogen-progestin oral contraceptives 3. Inhibition of ovulation
Published in Expert Review of Clinical Pharmacology, 2018
Carlo Bastianelli, Manuela Farris, Elena Rosato, Ivo Brosens, Giuseppe Benagiano
The action of this new progestin has been investigated in 13 healthy subjects to whom daily doses of 1.25, 2.5, or 5 mg were administered [44]. Nomegestrol acetate (NOMAC) inhibited ovulation in all women, with LH and P levels being constantly depressed. With 2.5 and 5 mg doses, plasma E2 remained low with high FSH values. With 1.25 mg, circulating levels of E2 were similar to those observed during the control follicular phase, with a concomitant decrease in FSH secretion. When the antigonadotropic activity of NOMAC was tested [45,46], it was found that it is not antagonized by flutamide and is not mediated via the androgen receptor. The exact mode of action of NOMAC was then investigated in 10 normally cycling women, 3 with McCune-Albright syndrome (MCA, characterized by gonadotropin-independent ovarian function), and 5 with functional hypothalamic amenorrhea. Ovulation was suppressed in all subjects when treated with 5 mg/daily NOMAC. In normal subjects, mean plasma LH levels, LH pulse frequency, and the LH response to exogenous GnRH were significantly decreased. A direct effect of NOMAC on the ovaries was ruled out, since in subjects with MCA syndrome, ovaries were unmodified. In subjects with functional hypothalamic amenorrhea, pulsatile GnRH administration recreated a normal ovulatory menstrual cycle, but administration of NOMAC prevented ovulation, as well as any increase in plasma E2, and decreased the amplitude of LH pulses. In a 6-month long trial at the daily dose of 5 mg, NOMAC significantly decreased E2 and P levels (p < 0.001) [47].