Progesterone is a naturally occurring steroid hormone. In nonpregnant women, the main sites of progesterone synthesis are the ovaries and the adrenal cortices. Because of the poor oral absorption of progesterone and its susceptibility to rapid first-pass metabolism in the liver, a variety of oral, injectable and implantable synthetic analogs, called "progestins," have been developed. Progestational agents have many important clinical functions, including regulation of the menstrual cycle, prevention of endometrial hyperplasia, treatment of abnormal uterine bleeding and contraception. Two hormones that are available over the counter are DHEA hormone and pregnenolone.

How's is Progesterone made?
The human body uses a natural hormone called pregnenolone to convert into progesterone. While progesterone is only available by prescription, pregnenolone is sold over the counter. The biological actions of pregnenolone somewhat overlap with that of pregnenolone.

Progesterone cream side effect
Q. Just wondering if you know if a side effect of the progesterone cream use can be rashes? Since starting the cream, I have broken out on my side, a wide area of welt-like rashes. I thought at first it was poison ivy, which I did have, but a doctor put me on a prednisone taper which cleared up the poison ivy, but the rash on my side persists. Just wondering if this could be a progesterone cream side effect.
   A. It is possible that one of the components of the progesterone cream is causing a rash as opposed to progesterone itself.

Function of progesterone
Progesterone plays an important role in postovulatory regulation of the menstrual cycle. Under the influence of luteinizing hormone, the corpus luteum secretes progesterone, which stimulates the endometrium to develop secretory glands. The corpus luteum produces progesterone for approximately 10 to 12 days of the cycle. If a fertilized ovum is not implanted, progesterone and estrogen levels decline sharply, resulting in menstrual bleeding. If fertilization occurs, progesterone supports implantation of the ovum and maintains the pregnancy.

Menstrual cycle
Progesterone plays an important role in postovulatory regulation of the menstrual cycle. Under the influence of luteinizing hormone, the corpus luteum secretes progesterone, which stimulates the endometrium to develop secretory glands. The corpus luteum produces progesterone for approximately 10 to 12 days of the cycle. If a fertilized ovum is not implanted, progesterone and estrogen levels decline sharply, resulting in menstrual bleeding. If fertilization occurs, progesterone supports implantation of the ovum and maintains the pregnancy.

Benefits

Anxiety
Allopregnanolone, the metabolite of progesterone, is a potent positive modulator of the GABA(A) receptor and produces sedative and anxiety reducing effects. Low dosages of this hormone can reduce anxiety while high dosages have the opposite effect.

Memory
Progesterone, or rather its neuroactive metabolite allopregnanolone, influences amygdala activity and thereby influences cognition and memory.

Progesterone and mood
It appears the influence of progesterone supplement, mood and anxiety is related to the dosage.

Allopregnanolone concentration and mood--a bimodal association in postmenopausal women treated with oral progesterone.
Psychopharmacology (Berl). 2006 Aug;187(2):209-21. Umeå Neurosteroid Research Center, Department of Clinical Science, Obstetrics and Gynecology, Norrlands University Hospital, SE-901 85, Umeå, Sweden.
Allopregnanolone is a neuroactive steroid with contradictory effects. Anaesthetic, sedative, and anxiolytic as well as aggressive and anxiogenic properties have been reported. The aim of this study is to compare severity of negative mood between women receiving different serum allopregnanolone concentrations during progesterone treatment. A randomized, placebo-controlled, double-blind, crossover study of postmenopausal women (n=43) treated with 2 mg estradiol daily during four treatment cycles. Oral micronized progesterone at 30, 60, and 200 mg/day, and placebo were added sequentially to each cycle. During progesterone treatment, women had significantly higher negative mood scores when allopregnanolone serum concentration was in the range of 1.5-2 nmol/l compared to lower and higher concentrations. In addition, women displayed a significant increase in negative mood during the progesterone treatment period, compared to the estradiol-only period when 30 mg progesterone daily was used. On the other hand, treatment with higher doses of progesterone had no influence on negative mood.Mood effects during progesterone treatment seem to be related to allopregnanolone concentration, and a bimodal association between allopregnanolone and adverse mood is evident.

Natural Progesterone
Natural progesterone is obtained from compounds derived from soybeans and Mexican yam roots, and occasionally from animal ovaries. The hormone is not available from any natural source without extraction and synthesis.

Oral Micronized Progesterone -- Micronizing is a process designed to increase the half-life of progesterone and reduce its destruction in the gastrointestinal tract. Micronization decreases particle size and enhances the dissolution of progesterone. Maximal serum concentrations are achieved more rapidly with orally administered micronized progesterone (Prometrium) than with injected progesterone. Absorption of micronized progesterone is enhanced twofold when the hormone is taken with food.

Natural progesterone source
Because of the reported side effects of synthetic analogs called "progestins," there has been interest in replicating the natural hormone for clinical use. Natural progesterone is obtained primarily from plant sources and is currently available in injectable, intravaginal and oral formulations. An oral micronized progesterone preparation has improved bioavailability and fewer reported side effects compared with synthetic progestins. Adolescents and perimenopausal women may require progestational agents for the treatment of dysfunctional uterine bleeding resulting from anovulatory cycles. These agents may also be used in women at risk for endometrial hyperplasia because of chronic unopposed estrogen stimulation. Progestin-only contraceptives can be used in women with contraindications to estrogen; however, efficacy requires rigorous compliance. New progestins for use in combination oral contraceptive pills were specifically developed to reduce androgenic symptoms. It is unclear whether these progestins increase the risk of venous thromboembolic disease.

Progesterone plays an important role in postovulatory regulation of the menstrual cycle. Under the influence of luteinizing hormone, the corpus luteum secretes progesterone, which stimulates the endometrium to develop secretory glands. The corpus luteum produces progesterone for approximately 10 to 12 days of the cycle. If a fertilized ovum is not implanted, progesterone and estrogen levels decline sharply, resulting in menstrual bleeding. If fertilization occurs, progesterone supports implantation of the ovum and maintains the pregnancy.

Herpes reactivation
Do you know of any connection between progesterone and the cold sore virus? I am a 70 year old woman still having hot flashes, night sweats and all the emotional crap that goes along with menopause. For 25 years I was using Premarin for this and also was told that it was good for my bones. Then when all the talk was about how bad it was for you, I tried to stop taking it several times before I finally could. I also was having heart palpatations by then and I truly believe they were caused by the long term use of Premarin. I tried several alternatives like Black Cohosh and other expensive herbs but nothing seemed to help me. Then I read Dr. John Lee's book about progesterone and found a doctor who would prescribe it for me. It was hard to get in Mexico, where I was living for a while, so I started ordering it off the internet. I did a lot of research and I'm sure all the product I bought was really natural progesterone and not progestin. Anyway, one of the sites I was reading on said not to use progesterone if you have the cold sore virus but it didn't expand on that and I never saw that information again anywhere and just kind of forgot about it. After using progesterone for about a year and a half I started to get cold sores continuously - they didn't always break out but I could feel them just under the skin and feel the nerve kind of thing in the side of my face. I also got them, or the sensation, on my bottom lip where they never were before. I stopped using the progesterone thinking that maybe I shouldn't be self-medicating and I didn't feel that it was helping all that much anyway but soon the hot flashes and the rest of was really out of control again and I felt like I was going crazy. My general doctor wouldn't have anything to do with bio-identical hormones and offered no other help other than all the things I'd already tried. After a few months I found someone to help me and we did a saliva test and now I'm once again taking progesterone but now also DHEA. Now the continual cold sores are back. Do you have any suggestions as to what I can do, at my age, for menopause symtoms other than progesterone?
    There does appear to be a connection.
 
Cherpes TL, Busch JL, Sheridan BS, Harvey SA, Hendricks RL. Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Clinical research suggests hormonal contraceptive use is associated with increased frequencies of HSV reactivation and shedding. We examined the effects of medroxyprogesterone acetate (MPA), the compound most commonly used for injectable hormonal contraception, on HSV type 1 (HSV-1) reactivation and CD8(+) T cell function in murine trigeminal ganglia. Our data suggest hormonal contraceptives that contain MPA may promote increased frequency of HSV reactivation from latency through the combinatory effects of inhibiting protective CD8(+) T cell responses and by a leukocyte-independent effect on infected neurons.

Natural progesterone questions
Q. I noticed that you do not mention wild yam as one of the supplements on your list. I have read that it is good for the stimulation of natural progesterone production. Do you agree with this? Also Dr. Ojeda recommends wild yam, chaste berry, sarsaparilla and yarrow do you concur with this?
   A. Wild yam is not converted into progesterone. We have not come across research as to whether wild yam stimulates natural progesterone release.

Q. I am 56 and born with Arthrogryposis (perhaps occurred in mom's womb but only diagnosed to me a year a go by an old and wise neurologist...doctors throughout my life wondered if I had polio but nobody was ever certain. (Arthrogryposis Multiplex Congenita) is a term describing the presence of a muscle disorder that causes multiple joint
contractures at birth. A contracture is a limitation in the range of motion of a joint. I work out and take vitamins. I know I am sensitive to drugs and do not take pain killers or any meds until recent Forteo shots...after menopause I tried to just take supplements. My main symptom was not sleeping much. Well I had a bone density test and it seems in 5 years I lost 20% bone mass... Anyway I have been taking Forteo shots for a year and my bone mass has increased 8%. I have a year to go and then the drug is no longer recommended...it supposedly has maxed out bone density increase. My doctor wanted me on estrogen, progesterone, and testosterone as my libido had gone to nothing and he says I need estrogen for my bones. So I am taking compounded troches, however I feel like a zombie...in 10 minutes I must sleep and I have trouble getting up after sleeping 9 hours...and am groggy all day and very tired...so they cut down progesterone to 1 mg. And no difference. So now they just put me on 25 mg pregnenolone. Is pregnenolone better than progesterone? How much should I take?
   A. We can't really provide individual advice regarding how much to take or what to take, but, as a general rule when it comes to hormones, one should take the least amount that works. We wish you an optimal outcome. There has not been enough research on pregnenolone to know whether it is better or worse than progesterone for various medical conditions.

Q. Regarding hyperemesis gravidorum. I have researched it and come to the conclusion it may be that their progesterone levels may be low. It seems that alot of the hyperemesis gravidorum symptoms go down to some extent after the first three months or so. this is when the progesterone levels naturally rise to as much as 10 times. which is one clue as to the first three months being the roughest. Also most of these women had PMS symptoms before pregnancy. Which is another clue that the progesterone is low during the first three months. (Progesterone is low in PMS). Why is taking doctors. so long to admit that women are being helped with natural progesterone and helping these women.
   A. See hyperemesis gravidarum.

Q.  I read this on the internet, and can you tell me if the following is an accurate description of the benefit of progesterone?
   "Many think that Progesterone is a female hormone, but it is not feminizing in men at all. Estrogen is the feminizing hormone in men. It is progesterone that is the natural antagonist to it. In men over 50 it is excess estrogen that causes breast growth and other problems. Progesterone can help inhibit this. Please do not confuse real natural progesterone with the progestin analogs like Provera that have serious side effects. Natural progesterone is completely different. Nature has given progesterone to men and women to balance and offset the strong effects of estrogen. Men have much lower levels of progesterone than women so they need less. Progesterone is very poorly absorbed orally and broken down into unwanted metabolites. Fortunately, it is readily absorbed by the skin into the blood so transdermal creams are very practical and effective. Get a good cream that contains 800 - 1000mg of real natural USP progesterone per two ounce jar (400-500mg per ounce) and states so clearly on the label. Apply a mere
1/8th teaspoon directly to your scrotum (testical sac) daily. This allows it to get into the prostate receptors. Progesterone has been shown to be non-toxic and very safe especially in these very low amounts. You will by applying about 7mg daily of which about 5mg will actually get into your system. Let's discuss the research to prove progesterone antagonizes estrogen, is a powerful 5-alpha reductase inhibitor (stops DHT formation) and that the
prostate has specific progesterone receptors that no other hormone can attach to. We will not list the journals, volumes and dates but the following studies were published in the most prestigeous medical journals in the world such as Endokrinologie, Indian Journal of Experimental Biology, Gynecological Investigation, International Encyclopedia of Pharmacological Therapy, Acta Endocrinology, Journal of Clinical Endocrinology and Metabolism, Journal of Endocrinology, Journal of Steroid Biochemistry, Oncology, Annals Endocrinology, Acta Physiologica
Latinoamerica, Prostate, Urology Research, Endocrinology and Archives of Gerontology and Geriatrics.
   A. We have not seen much evidence that progesterone use in men is beneficial for prostate health or hair growth. If one were to use progesterone, natural progesterone is probably preferable to synthetic Provera. We have not seen any long term clinical trials regarding progesterone use in males to determine whether progesterone pills or cream are useful, beneficial or appropriate. There should be a good reason to use hormones since misuse can cause short term and long term side effects.

Q. I have been using a natural progesterone cream for about 2 months. It has herbs in the cream also. I have been using it as directed as far as number of days per month. It said to rub it in 2 times a day and I have been using it twice a day. Each application dispenses 20 mg of USP progesterone. It says to apply it to the chest, inner thighs, and inner arms or wrists. I alternate where I put it. My problem is I have started getting small round red raised moles at the spots I have been rubbing the cream on. What is causing this problem? Does this mean I can't use this product? Is it one of the herbs in the cream or the progesterone that is causing the problem? It can't be from sun exposure as I have not been out in the sun since I started using it.
   A. We can't say for sure since we don't know what the product is and what the herbs are or how they are mixed or what other ingredients are added to the progesterone cream. You may wish to ask the manufacturer directly. You may also with to try a different progesterone cream product which only has progesterone and no herbs to see if the same thing happens. If it does, it may be due to the progesterone itself as opposed to another ingredient within the cream.

Q. I am on no prescription medication at all. The one thing I do is use progesterone cream for 3 weeks per month. Have you heard of any difficulties taking Pycnogenol supplement with the progesterone cream?
   A. Much of supplement interactions depend on dosages and the person who is taking them. In low dosages, most supplements and hormones do not interact greatly, but each person is unique and the whole body and mind have to be considered rather than the limited information provided.

Q. I was wondering if you have any information on Progensa Progesterone Cream. On their website the claims are that Progensa Progesterone Cream is a remedy for: Uterine Fibroids Menopause Endometriosis PMDD Premenstrual Dysphoric Disorder  PCOS-Polycystic Ovary Syndrome Estrogen Dominance Irregular Bleeding Anovulation (Lack of Ovulation) Luteal Phase Defect/Infertility Premenstrual & Chronic Headaches Depression, Anxiety & Sadness Vaginal Dryness Urinary Incontinence Skin Conditions  Weight Gain Breast Pain Sleep Difficulties Low Sex Drive and Hot Flashes.
   A. We are not familiar with this progesterone product. But, we are suspicious about these claims since many medical conditions besides hormone issues can cause these problems and progesterone may not be a solution for them. Furthermore, the company selling this product on their website is violating FDA rules by making claims that their product can treat or cure a medical condition.

Q. Is vaginal micronized progesterone and effective way to deliver progesterone?
   A. Yes, vaginal micronized progesterone is a good option.

Q. I saw your page on progesterone hormone supplement and most of the questions submitted were dealing with menopause. My husband and I are both young (early 20s) and active with no health complications that we know of. We have been trying to conceive for several months now with no luck (we use Natural Family Planning, so we know when-abouts I'm ovulating). I have brown bleeding the last few days of my period (I have always had this since my very first period I'm pretty certain) and a very low libido (again- always have). Post- ovulation my cycle length varies from 3 days post ovulation (this was just last month) to 16 days post ovulation, but typically its around 10-12! I asked my doctor about getting my progesterone levels tested and she said- even if I had low progesterone there is nothing they can do about and that all of my symptoms are most likely related to something else, so she wouldn't even test me! So, I ordered Source Natural's Progesterone Cream and have been using it this cycle (I only use it from 3 days post ovulation until my period starts). I'm a little concerned- the container says the chemical is known to cause cancer- should I be worried? And, is there anything else I can be taking to help with conceiving?
   A. See fertility. Long term use of hormones, including progesterone, may lead to a variety of health issues. It is possible that the risk for cancer is increased by the long term use of progesterone when done so for several years.

I've read that it's very important to avoid all estrogens and xenoestrogens while using natural progesterone. Of course, pollution, in general, is unavoidable but I would like to hear your views on this.
    We have not seen any studies that would support this view. The need to use natural progesterone depends on many factors and there are no simple answers since each person is different on whether they need it, at what dosage, and for how long, and whether they would benefit taking it with or without estrogens.
        I am not questioning my need to use natural progesterone; I have had my hormone levels tested (saliva test), plus a whole host of others, and everything points to me being a prime candidate for natural progesterone supplementation, (not to mention the way I feel as a postmenopausal woman). I'm just not sure how important it is to avoid phytoestrogens and xenoestrogens - of course, each of us is different and, as such, will respond differently to any given substance for a variety of reasons. There are some websites, one by Dr. Elizabeth Smith, M.D. that recommends avoiding all estrogens. Dr. Elizabeth Smith, M.D. says, "Failure is almost guaranteed when estrogens and xenoestrogens are not cut out of the patient's environment." The Women's Therapeutic Institute, which promotes Progestelle, is emphatic about avoiding xenoestrogens. I intend to purchase a brand of natural progesterone, and want to make sure I'm maximising both my chances of relative well-being, and my money; that means doing the research.
            Saliva testing may not be a reliable way to know whether or how much progesterone to use. We have seen no human evidence that xenoestrogens or phytoestrogens inhibit the effects of progesterone cream.

I have been titrating slowly off klonopin after 14 yrs usage at .5 mgs  I had done two detoxes and made me so sick I reinstated and found out that one is to go slow off it. I have been going slow since dec 6th of 2008 so it has been a year now and got from .5 to .107 painfully slow by putting the pill in 40 mil of milk and then withdrawaling 1/10th a mil a day and holding at times, I am 56 and also menopausal and my estrogen is 28 and progestrone is .6, my doc thinks I should take bio identical hormones to help out my brain but I do not know if this is the trouble or would harm me more coming off the klonopin. Here is where I am desperate..4 months ago I had my plasma catecholamines cked the urine was within range the blood showed that the norpehenephrine was 894 and dopamine was 30 and I was admitted to the hospital to ck for tumors in the adrenal glands the lower I go on the klonopin seems I am more anxious and this is a worry. then two months later the norephenephrine lowered to 594 today I got new tests and my norephenephrine is now 959! ( normal range is 80 to 520) so what does this mean? my dopamine is 34 which is high too as the range is 0 - 20 epinephrine is 27 within range but on the low end as the range is 10-200. Please tell me what to do here? I am very uncomfortable and frightenedl I am worse in the morings and my cortisol levels are high in the mornings higher than normal .like 27 .is this from withdrawal from the klonopin? this whole mess? what do I do? I am so anxious and these levels are causing this to be hard on me, please say how to lower this.
    We are sorry but we are not able to provide individual advice, but perhaps the page on anxiety can help you and you can discuss the options with your doctor.

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