Fetal programming
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
Progestin is a component of oral contraceptive pills (OCP) and limited exposure during the periconceptual period occurs with failure of oral contraception. Continued use of OCPs until detection of pregnancy occurs in 2% to 5% of pregnancies and can expose fetuses to exogenous hormones during critical windows of fetal development (42). In addition, emergency contraception exposes fetuses to even higher doses of exogenous hormones and is not 100% effective at preventing implantation. Prior to the advent of modern pregnancy tests that detect human chorionic gonadotropin in urine, the major indication for progestins in pregnancy occurred from progestin administration for 3 to 5 days to induce withdrawal menstruation. Today, the major indications for progestin therapy are to prevent preterm birth and treat recurrent pregnancy loss. Progestin supplementation is also utilized in assisted reproduction protocols to promote endometrial development favorable for implantation of a transferred embryo.
Endocrine, paracrine and intracrine mechanisms of growth regulation in normal and malignant breast epithelium
A. R. Genazzani in Hormone Replacement Therapy and Cancer, 2020
Progestins can have important effects in other tissues besides the endometrium, including the breast, liver, bone and brain. The biological responses of progestins cover a very large domain: lipids, carbohydrates, proteins, water and electrolyte regulation, hemostasis, fibrinolysis, and cardiovascular and immunological systems. The action of progestins depends upon the administration route (e.g. oral, vaginal) as well as the dose used. Generally, progestins are rapidly absorbed, with a maximum plasma concentration occurring within 2–5 h; they are metabolized mainly in the liver and have a longer half-life than progesterone. The responses to individual progestins may depend on their structure, metabolism, receptor affinity, experimental conditions, target tissue or cell line, as well as the biological response considered.
Chronic Pelvic Pain
Mark V. Boswell, B. Eliot Cole in Weiner's Pain Management, 2005
Progestins induce decidualization and decrease the proliferation of endometriotic tissues. Medroxyprogesterone acetate in a 50 mg oral daily dose has been found to be just as effective at reducing pelvic pain as danazol, as danazol and an oral contraceptive, and as compared with a GnRH-a in randomized trials, although the effects regress after 6 to 12 months (Fedele et al., 1989; Vercellini et al., 1993; Walton & Batra, 1992). A Cochrane Review article recently concluded that both continuous progestins and antiprogestins (mifepristone, RU-486) are effective in the treatment of painful symptoms of endometriosis. Progestins given in the luteal phase have not been shown to be effective (Prentice et al., 2003). Mifepristone, 50 to 100 mg/day, was shown to decrease pain scores and induce amenorrhea without hypoestrogenism in small, openlabel, cohort studies (Kettel et al., 1996). Progestin side effects include weight gain, breast atrophy, hot flushes, and hirsutism (Rice, 2002).
A focused report on progestogen hypersensitivity
Published in Expert Review of Clinical Immunology, 2023
Diti H. Patel, Lauren M. Fine, Jonathan A. Bernstein
Progesterone, the main progestogen in the human body, is a steroid hormone derived from cholesterol, and is uniquely composed of 21-carbon atoms. The term ‘progestogen’ refers to any natural or synthetic form of progesterone. The term ‘progestin’ is specific for synthetic progestogens. Progesterone has a spectrum of metabolic and physiologic roles on various organ systems, especially within the reproductive system. It is produced by granulosa cells in the corpus luteum, and one of its primary responsibilities is the maintenance of the endometrial thickness prior to menses. The increase in progesterone during the menstrual cycle occurs due to a luteal hormone (LH) surge, marking the beginning of the luteal phase. When pregnancy occurs, the placenta becomes the primary source of progesterone at around 10 weeks gestation. Progesterone plays a vital role in maintaining the uterus during pregnancy by decreasing the myometrial tone, increasing spiral artery development, and inhibiting prolactin release. Aside from its responsibilities in the reproductive system, progesterone acts on the hypothalamus to increase body temperature and help regulate the immune system. This latter function occurs through the production of inflammatory cytokines by T lymphocytes [4,5] as well as binding to progesterone receptors on mast cells [6]. However, it is still unclear if and how the impact of progesterone on the immune system in normal biology may contribute to the development of hypersensitivity response to progesterone.
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
Progestins are classified in categories according to their structural origins. They have been divided in generations according to the time of first synthesis. Among those used in the field of HC, pregnanes (17-hydroxyprogesterone derivatives and 19-norprogesterone derivatives, i.e. chlormadinone acetate) and estranes (testosterone derivatives, i.e. norethindrone, norethynodrel, norethindrone acetate, and ethynodiol diacetate) are considered first generation progestins. Only few of these are still used in HC due to their androgenic properties that cause bothersome side effects, as oily skin, acne, and reduced levels of high density lipoproteins (HDL) [30]. Second-generation progestins are called gonanes and derive from testosterone. This includes some of the most widely used progestins, such as levonorgestrel. Third generation include desogestrel, gestodene, norgestimate/norelgestromin, and etonogestrel. These molecules progressively lose the androgenic activity, acquiring a non-androgenic or an antiandrogenic effect. The newest progestins are the fourth-generation ones, that include nonethylated estranes (i.e. dienogest and drospirenone, a spironolactone derivative) and 19-norprogesterones-derivatives pregnanes (i.e. nomegestrol acetate) [29–31].
Neurodevelopmental disorders in children exposed in utero to synthetic progestins: analysis from the national cohort of the Hhorages Association*
Published in Gynecological Endocrinology, 2019
Marie-Odile Soyer-Gobillard, Laura Gaspari, Philippe Courtet, Mauricette Puillandre, Françoise Paris, Charles Sultan
Although a direct relationship cannot be formulated, a link between progestin treatment during fetal life and later psychiatric disorders in offspring should be considered. Since progestins are known to induce GABA receptor activity/neural activation before birth, it is likely that the GABAergic system contributes to schizophrenia, anxiety, depression, panic disorders, epilepsy, autism, and other disorders [24]. Disruption of GABA signaling in early development alters cell migration and cortical architecture, which then may lead to chronic disability in postnatal life. Our results point out the postnatal consequences of synthetic progestin treatment during fetal life and highlight the potential impact of synthetic progestin. They highlight the need for reevaluation of the potential outcome of progestin administration during gestation.
Related Knowledge Centers
- Fertility
- Organic Compound
- Progesterone
- Pregnancy
- Medication
- Natural Product
- Sex Hormone
- Hormonal Contraception
- Hormone Replacement Therapy
- Gynaecology